Supplement 2 2022
The prevalence, characteristics and complications of mesiodens in non-syndromic pediatric patients
Esra Kızılcı, İsmail Cihangir
Department of Pedodontics, Faculty of Dentistry, Erciyes University, Kayseri, Turkey
DOI: 10.4328/ACAM.21286 Received: 2022-06-26 Accepted: 2022-07-28 Published Online: 2022-08-01 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S71-75
Corresponding Author: Esra Kızılcı, Erciyes Universitesi, Diş Hekimliği Fakültesi Pedodonti Anabilim Dalı, 38000, Melikgazi, Kayseri, Türkiye. E-mail: esra_ayhan85@hotmail.com P: +90 505 623 22 85 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0746-7087
Aim: This study aims to determine the prevalence of mesiodens in pediatric patients, and to examine the characteristics of mesiodens and the associated complications.
Material and Methods: Panoramic radiographs of patients aged between 5-14 years who presented to the Pediatric Dentistry Department between 2012-2019 were analyzed. Among 54895 patients, 319 were found to have 355 mesiodens. The morphology, location, eruption stage and the associated complications of mesiodens were analyzed.
Results: The prevalence of mesiodens was found to be 0.58 %. Two hundred and twelve patients were male (66 %), 238 were in the mixed dentition stage (74.6%); 89 % of the patients (n=284) had a single mesiodens, 10.7 % had 2 and one had 3 mesiodens. Conical morphology (n=225, 63.4 %), vertical position (n=233, 65.6 %) and impaction (n=180, 50.8 %) were found to be common in mesiodens. Complications associated with mesiodens were identified as diastema (21.9 %), rotation/displacement of the adjacent tooth (14.4 %), and presence of resorption (2.6 %). 61.1 % of mesiodens were found to be asymptomatic.
Discussion: Although the prevalence value is similar to other studies in the literature review, it is closer to the studies on X children. Since the presence of diastema is the most common complication, radiographs should be carefully examined for the presence of mesiodens in a routine examination. Dentists need to be attentive in clinical examination to be able to prevent complications in the early stages.
Keywords: Mesiodens, Supernumerary Tooth, Prevalence, Characteristics, Complications
Introduction
Supernumerary teeth are considered as a developmental anomaly that exists in addition to the regular teeth in the mouth [1]. Although their etiology is not fully known, different views have been suggested. These are the phylogenetic theory, the dichotomy theory and the hyperactivity theory. The first and the oldest is the Phylogenetic theory, which is discarded today, and it states that mesiodens is a relic of our ancestors who had three central incisors [2]. The dichotomy theory explains this as the division that occurs in the tooth bud to form two different teeth [3]. The most widely accepted theory is the hyperactivity theory, which suggests that mesiodens might emerge due to local, independent, and conditioned hyperactivity of the dental lamina that leads to the proliferation of remnants of the dental lamina [4].
Mesiodens may accompany syndromes such as cleidocranial dysplasia, Gardner syndrome, and cleft lip and palate or may be observed in non-syndromic individuals [5]. The most common type of supernumerary teeth includes teeth in the maxillary midline and are called mesiodens. They have an incidence rate of 80% among all supernumerary teeth [6].
Although it varies depending on the diagnosis methods and the differences in examined populations, studies have reported that the prevalence of mesiodens is between 0.1-1.9%. It is more common in boys than in girls [7]. Mesiodens can be seen singly in the midline or multiple unilaterally or bilaterally [3,8]. Mesiodens can show different morphological features. Conical, tuberculate, supplemental and odontoma are the commonly observed forms. The most common of these is the conical form [7, 9] .
Clinical examination is not sufficient to diagnose mesiodens. Additionally, periapical, occlusal and panoramic radiographs are helpful in early diagnosis [10]. The ‘same-lingual, opposite-buccal’ technique is a diagnostic tool for obtaining information about the positions of the teeth [3]. On the other hand, cone-beam computed tomography (CBCT) scans reflect both the position and shape of the mesiodens and the relation of mesiodens with surrounding structures in 3D. This is important in deciding on a development of an appropriate treatment plan [1,8].
While mesiodens may be asymptomatic, they may also cause various problems [11]. Midline diastema, obstructing the eruption of permanent teeth, malformations such as root dilatation of permanent teeth, space restriction in the dental arch, or crowding are examples of these problems. On the other hand, they may cause orthodontic problems in the future. Besides, conditions that may require surgical intervention such as cyst formation and root resorption may occur [1,4,12].
Mesiodens may be asymptomatic or may cause various problems in the oral cavity. This study aims to examine the prevalence, characteristics, and associated complications of the mesiodens in the Turkish population in the Central Anatolia region, as the prevalence varies according to the population studied. We think that involving a high number of patients in the study is important in terms of understanding the prevalence of mesiodens. The null hypothesis of the study is that mesiodens may also appear in non-syndromic patients, and different prevalences can be observed in different regions within the same population.
Material and Methods
Ethics committee approval for the study was obtained from the Erciyes University Non-Invasive Clinical Research ethics committee (Ethics approval number: 2021/102, Date: 03.02.2021). The study was carried out by examining panoramic radiographs of 54895 pediatric patients who visited the Erciyes University Faculty of Dentistry, Department of Pedodontics between 2012-2019. Patients between the ages of 5-14 were included in the study.
Inclusion-exclusion criteria
Digital panoramic radiographs (OPG X-ray machine) (71kv, 16ma, 13.4s; Instrumentarium op200D, Kavo Kerr, Germany) taken for examination and diagnosis from the patients who came for routine dental examination were included in the study. The patients were not requested to take radiographs for the study. Among the radiographs examined, those with poor image quality were excluded from the study. During anamnesis and clinical examination, patients with a history of tooth loss due to extraction or trauma were not included in the study. If the patient had multiple OPGs, only one OPG was included per patient. Syndromic cases with systemic diseases such as cleft lip/palate, Williams syndrome, Gardner syndrome, cleidocranial dysplasia, etc. were excluded from the study because of the association with the presence of supernumerary teeth. Two hundred seventeen of the 55112 OPGs examined in this context were excluded from the study.
Study design
Supernumerary teeth that exist in the region between the long axes of the upper central teeth were accepted as mesiodens in this study. Panoramic radiographs of the pediatric patients were examined (C. I.), and then checked by the second researcher (K. E.). Cases in which there was a difference of opinion were re-evaluated and a consensus was reached. The assessments were made at two different times on radiographs. The initial and repeated whole assessments performed by the examiners showed that the intra- and inter-examiner agreement ranged from 0.964 to 0.981 and 0.972 to 0.990, respectively according to Cohen’s Kappa (κ>0.75 is evaluated as a good agreement).
In addition to demographic indicators such as age and gender, patients’ dentition stages (primary, mixed, and permanent dentition) were recorded. Also, the number of mesiodens and concomitant supernumerary teeth were examined. The state of the eruption of the determined mesiodens (erupted/impacted), crown shape (conical, tuberculate, supplemental, and dysmorphic), position (horizontal, vertical, and inverted), and clinical complications caused by mesiodens in patients (presence of diastema, presence of cystic structure, rotation in the adjacent tooth, and root resorption) were examined. Periapical radiographs and clinical notes were consulted if complications were suspected.
Statistics
Patient data were recorded in SPSS 12 (IBM Corp; 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY, USA) for statistical analysis. The evaluations, descriptive analyses, and comparisons between the gender were made using the chi-square test.
Results
In the examined panoramic radiographs of the 54895 patients, 0.63% (n=319) of the patients were found to have mesiodens. The mean age of 319 patients aged 5-14 years was 8.53±2.25 years. One hundred seven of the patients were female and 212 were male. There was a statistically significant difference between gender and the presence of mesiodens (p<0.05). It is seen that 238 of the patients (74.6%) were in the mixed dentition, 26 (8.2%) were in the primary dentition and 55 (17.2%) were in the permanent dentition.
In patients with mesiodens, a total of 355 mesiodens were recorded; one in 284 patients, two in 34 patients and three in one patient (Figure 1). Seven patients had one supernumerary tooth in addition to mesiodens; one patient had additionally four supernumerary teeth (Figure 2).
The conical shape (n = 225, 63.4%) was found to be the most common group when the crown shape of 355 mesiodens was examined. The remaining ones were supplemental: 43 (12.1%), tuberculate: 71 (20%) and dysmorphic/odontoma: 16 (4.5%). The state of the eruption of mesiodens according to the crown shapes is shown in Table 1.
One hundred seventy-five of the mesiodens (49.2%) were seen in the oral cavity, and 180 (50.8%) of them were impacted. There was no statistically significant difference between the eruption of the mesiodens and the presence of clinical complications (p>0.05).
In clinical complications associated with mesiodens, midline diastema in 70 patients (21.9%), rotation/ displacement of the tooth adjacent to the mesiodens in 46 patients (14.4%) and resorption in the adjacent tooth roots in eight patients (2.6%) were seen. No formation of cyst/cystic structure associated with diastema was observed. In 195 patients (61.1%), mesiodens was asymptomatic, there were no associated complications.
Discussion
In the study, panoramic radiographs of 54895 pediatric patients were examined, and the mesiodens prevalence, characteristics and complications associated with mesiodens were determined. The reported prevalence of mesiodens in the literature varies between 0.1 and 1.9% [7,12,13]. Previous studies have found that the prevalence of mesiodens was 1.4% (North India) according to Patil et al. [13], and 1.6% (Mexico) according to Salcido-García et al [14]. In studies conducted on Turkish patients, the rate was between 0.13 and 0.3. [7, 15, 16]. In our study conducted on patients in Turkey’ s Central Anatolia, the prevalence was found to be 0.58%, which is within the range of overall prevalence rate and consistent with other studies conducted in Turkey.
The mean age of patients with mesiodens was 8.53 years and most of them were in the mixed dentition. Aren et al. found the average age in their study as [16] 9.5 years. Routine examinations of central teeth or delayed eruption or impaction of the incisor were evaluated in this age group. Therefore, the average age of the patients is within this range in most of the literature. In addition, it has been reported that mesiodens affects both teeth equally, however, it occurs more frequently in permanent teeth. The fact that the period in which the primary dentition ends and the permanent teeth begin to erupt coincides with the mean age that was found in this study is in accordance with the literature.
Studies report that the mesiodens appears more often in boys. Nonetheless, Colak et al. [7] found that, in contrary to the general findings, mesiodens was more frequent in women. Zhao et al. found that the male to female ratio was 2.9:1 [17] and 2.3:1 according to Aren et al. [16]. Similar to previous studies, the male to female ratio was 2.1:1 in our study.
Mesiodens can occur singly or multiply. According to the literature, a single mesiodens is more common, and except for non-syndromic individuals, multiple mesiodens are rare. Asaumi et al. [6] and Gündüz et al. [15] reported mostly single mesiodens in the patients. In some studies, no triple mesiodens could be found [12,13]. In addition, no studies reported more than triple mesiodens. In this study, 89% of the patients had a single mesiodens, 10.7% had two mesiodens, and 0.3% had triple mesiodens.
Mesiodens vary in shape and are generally classified as conical, tuberculate, supplemental and dysmorphic/odontoma-like [4]. In accordance with similar studies in the literature, conical-shaped mesiodens was found to be the most common in this study [16-18]. Following conical mesiodens, in terms of prevalence, Altan et al. [18] reported supplemental, tuberculate mesiodens, and Aren et al. [16] reported tuberculate, supplemental mesiodens. In addition, in many studies, odontoma/dysmorphic mesiodens was not included in the morphological classifications [12, 16, 18, 19]. In this study, the most common shapes after conical mesiodens are supplemental, tuberculate, and odontoma-like mesiodens, respectively.
Altan et al. reported that the eruption rate was the highest in conical mesiodens, while it was the lowest in tuberculate ones in their study [18]. In this study, the eruption was 81% in supplemental mesiodens, 45% in conical mesiodens, and 26% in tuberculate mesiodens. In addition, none of the 16 dysmorphic/odontoma-shaped mesiodens were erupted. The morphology of supplementary mesiodens resembles teeth, and they usually develop roots fully, which explains why they are the most likely to erupt. The morphology of conical mesiodens, which is more likely to erupt than tuberculate mesiodens, and the failure of eruption due to arrested root formation in odontoma shape explain the findings of this study. However, more studies are needed on the relation between tooth morphology and eruption.
In one study, supplemental mesiodens was found to be more common in the permanent dentition than in the primary dentition [18]. In this study, conical mesiodens was found to be more common in both dentition stages. However, the majority of the patients in this study were in the mixed dentition (74.6%), and the number of patients was not adequate to examine the primary and permanent dentitions.
Mesiodens are mostly vertical, but can also be found horizontal, semi-vertical, or inverted [15,20]. Aren et al. [16] found the rate of mesiodens in vertical position as 77.1%, Altan et al. [18] as 76.8%, and Göksel et al. as 63% [21]. Similar to these values, the rate of vertical position was found to be 66.2% in this study. 13% the mesiodens were inverted, 11.5% were horizontal and 9.3% were semi-vertical. Contrary to the findings of this study, Asaumi et al. [6] found the vertical mesiodens ratio as 27%. In addition, Roychoudhury et al. found more inverted mesiodens in their studies [22].
Complications associated with mesiodens in our study are as follows: diastema (21.9%), rotation/displacement of the adjacent tooth (14.4%), resorption in the adjacent tooth root (2.6%) and cystic structure formation. However, it was seen that 61.1% of the examined mesiodens were asymptomatic. In accordance with the findings, Altan et al. and Lee et al. found the most common complication to be diastema [18, 23]. Dinkar et al. report that there is a correlation between mesiodens and dentigerous cysts [24]. Nonetheless, while Lee et al. [23] found only 0.5% dentigerous cysts in their study, no cystic structures associated with mesiodens were observed in this study. According to a study, supplemental mesiodens cause a diastema, and conical mesiodens cause complications of displacement/rotation [19]. In this study, it is seen that supplementary teeth mostly (74.4%) cause diastema. However, since most of the examined mesiodens were conical, they were encountered the most in all complications.
While planning the treatment, mesiodens should be subjected to a thorough clinical examination and radiographic evaluation. The decision of clinical follow-up or extraction can be then made accordingly [25]. Unerupted and asymptomatic mesiodens that do not exhibit any complications may not need surgical extraction. They can be kept under observation with regular clinical follow-up. However, if the mesiodens damage the anatomical structures in the region they are located in, adversely affect the comfort and aesthetics of the patient and prevent the treatment plan of the patient with orthodontic needs, they will need to be removed [18]. Despite the limitations of examining a patient group in a particular region, we think that involving a high number of patients in the study is important in terms of understanding the prevalence of mesiodens and its complications.
Limitations
The diagnosis of mesiodens with the OPG method provides limited evidence about the shape and complications of the mesiodens in terms of unclarity in the midline region. Not using 3D imaging in the study is one of the limitations of the study.
Conclusion
In this study in which panoramic radiographs of the non-syndromic patient population were examined, the prevalence of mesiodens was found to be similar to other studies. Since the presence of a diastema is the most common complication when detected at a routine examination, the patient should be examined for the presence of mesiodens. It was seen that the majority of the mesiodens were unerupted. This finding reveals that a thorough clinical examination and radiographic evaluation are necessary to diagnose mesiodens. Undesirable complications such as diastema, cyst formation and resorption of adjacent teeth can be eliminated with early diagnosis and timely intervention (extraction, follow-up, etc.). Dentists, pedodontists and orthodontists need to be attentive in clinical examination to be able to prevent complications and malocclusions in the early stages. We consider that it will be important to perform the study in large populations with techniques of tomography that provide better imaging in the anterior region to obtain more general results.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Esra Kızılcı, İsmail Cihangir. The prevalence, characteristics and complications of mesiodens in non-syndromic pediatric patients. Ann Clin Anal Med 2022;13(Suppl. 2):S71-75
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The role of endocan and immature granulocyte in the diagnosis of acute pancreatitis
Esat Taylan Ugurlu 1, Tulin Yazici 2, Ugur Fahri Yurekli 2
1 Department of General Surgery, 2 Department of Biochemistry, S.B.Ü. Sanliurfa Mehmet Akif Inan Education and Research Hospital, Sanliurfa, Turkey
DOI: 10.4328/ACAM.21313 Received: 2022-07-15 Accepted: 2022-08-15 Published Online: 2022-10-05 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S76-79
Corresponding Author: Esat Taylan Ugurlu, Department of General Surgery, S.B.Ü. Sanliurfa Mehmet Akif Inan Education and Research Hospital, 63100, Sanliurfa, Turkey. E-mail: doktoramca_1971@hotmail.com P: +90 531 905 25 77 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5273-1583
Aim: Acute pancreatitis is an inflammatory disease. It can progress from mild forms to serious life-threatening cases. Early diagnosis and treatment are critical for prognosis. In this study, we aimed to investigate whether serum endocan, immature granulocyte percentage (IG%) and CRP (C Reactive Protein) could be used as biomarkers in the early diagnosis of acute pancreatitis.
Material and Method: Patients diagnosed with AP (n=90) and individuals diagnosed with biliary obstruction due to choledochal stones (but not developed AP) (n=90) were included in this study. Serum endocan, IG% and CRP levels were measured
Results: Endocan, IG and CRP were found to be significantly higher in AP patients compared to controls (p<0.0001). According to the ROC analysis result, CRP (AUROC: 0.997) can be used to estimate AP, but endocan (AUROC: 0.638) and IG% (AUROC: 0.626) sensitivity-specificity is low
Discussion: CRP is an effective marker in the diagnosis of AP. Endocan and IG% are not effective in the diagnosis of AP because their sensitivity-specificity is low in the diagnosis of AP.
Keywords: Acute Pancreatitis, Endocan, Immature Granulocyte Percentage
Introduction
Acute Pancreatitis (AP) is an inflammatory process of the pancreas that progresses with abdominal pain, elevated amylase and lipase [1]. Any delay in diagnosis and treatment leads to an increase in morbidity and mortality rates. Early diagnosis of AP requires a fast and reliable biomarker. Although various inflammation markers (C-reactive protein [CRP], procalcitonin, neutrophil-lymphocyte ratio [NLR]) and complex scoring systems have been developed for this purpose, there is no ideal method yet [1].
Studies have shown that endocan plays a key role in inflammation, and serum levels increase in case of inflammation [2]. Endocan levels were found to be associated with the presence and degree of inflammation and response to treatment [2].
The percentage of immature granulocyte (IG%) is a new inflammation marker that is not sufficiently known to most clinicians [3]. The detection of immature granulocytes in peripheral blood, which is not normally seen in healthy people, is an indicator of bone marrow activation and serious infection [3].
CRP is an acute phase reactant secreted against Interleukin (IL) 1 and IL-6 in the liver. CRP >150 mg/L in the first 48 hours may be helpful in the diagnosis of severe AP. In the first 48 hours (CRP>150 mg/L), the sensitivity was 80% and the specificity was 76% [4]. It is the most useful of the biochemical markers used to determine the severity and complications of AP [5].The biggest disadvantage is that the increases that occur after 72 hours are delayed and do not peak immediately after the onset of symptoms [5]. Despite this, CRP elevation in the first 48 hours is widely used because it is a cheap and reliable test that determines the severity of AP [5].
The aim of this study is to determine whether endocan and IG%, which are inflammation markers, can be used as biomarkers in the early prediction of AP severity.
Material and Methods
The study was approved by the Harran University Clinical Research Ethics Committee with the decision number HRU.22.07.27.
In this study, patients (n=90) admitted to Şanlıurfa Mehmet Akif İnan Training and Research Hospital with the diagnosis of AP between April and July 2022 and the control group (n=90) who did not have AP, who had no signs of infection in their examinations, and who were diagnosed with choledochal obstruction due to choledochal stones were included.
Blood samples were taken from patients diagnosed with AP within the first 24 hours of their admission to the hospital to measure serum endocan, IG% and CRP levels. To determine the endocan and CRP levels, blood samples were taken into serum separation tubes and centrifuged at 1000G for 15 minutes. The obtained serum samples were transferred to new tubes and stored at -80 °C until measurement. Blood samples for IG% were immediately analyzed in whole blood analysis tubes with EDTA. Blood samples in the control group were collected and analyzed similarly to the patient group.
Endocan was analyzed using the human ESM1 ELISA kit (Jiaxing, Zhejiang, China). CRP was analyzed with the Roche Cobas c 6000 instrument (Roche Diagnostics GmbH, Germany). %IG was analyzed with Sysmex XN2000 (Sysmex Inc., Japan). Endocan, IG% and CRP levels obtained from the patient and control groups were compared with the appropriate statistical method.
Statistical Analysis:
Data were evaluated using the IBM SPSS Statistics 20.0 package software (IBM, New York, USA). Data were given as number of units (n), percent (%) and mean±standard deviation. Statistical analyzes were performed using the chi-square test and the Mann-Whitney test depending on the appropriate variable. Receiver operating characteristic (ROC) analysis was performed to determine the success of endocan, IG% and CRP in predicting AP. P- value of <0.05 was considered significant. Statistical tests performed on the parameters are given in Tables 1 and 2.
Results
Of the 90 patients included in our study, 24 (26.7%) were male and 66 (73.3%) were female. The age of our patients ranged from 19 to 94 years, and the mean age was 55.67±18.94 years. Of the 90 patients in our control group, 32 (35.6%) were male and 58 (64.4%) were female. The age of our patients in our control group ranged from 20 to 94 years, and the mean age was 54.13±21.45 years.
Demographic and clinical characteristics of the groups are presented in Table 1. There was no significant difference in gender (p=0.36) and average age between the study and control groups (p=0.71).
When compared to the control group (Non AP), serum endocan, IG% and CRP levels were found to be significantly higher in the AP group (p=0,018; p=0.031, p<0,0001, respectively) (Table 1 and Figure 1).
The efficiency of endocan, IG% and CRP parameters in AP prediction was calculated using receiver operating characteristic (ROC) curves. The results obtained by comparing the areas under the ROC curve are given in Table 2 and Figure 2. According to ROC analysis results, endocan >872.5 ng/L (Sensitivity 57,14%; specificity 69.39%; p=0.018), IG >0.61% (Sensitivity 65,31%; specificity 59.18%; p=0.03) and CRP >23.95 (mg/L) (Sensitivity 100%; specificity 93.88%; p<0,0001) were determined as cut-off values for AP estimation (Table 2 and Figure 2).
Discussion
In this study, it was shown for the first time that endocan is not effective in the diagnosis of AP. It has been shown that IG% cannot be used because it is not a strong enough biomarker in the diagnosis of AP. Scoring systems and imaging methods may not provide sufficient information to determine the AP, other parameters are needed. Inflammation plays an important role in AP pathogenesis, and inflammation markers may be important in determining AP [6]. Serum pancreatic enzyme (amylase, lipase) measurements are the “gold standard” in the diagnosis of pancreatitis, but both may increase in non-pancreatitis cases; however, lipase was still found to be more specific [7]. The cutoff value for diagnosis is that these enzymes have risen more than 3 times the normal upper limit [7].
Predicting the severity of the disease plays an important role in the treatment of AP. More than 80% of AP attacks are mild, self-limited, and resolve without serious complications. Early recognition of patients is very important to prevent morbidity and mortality. It is difficult to predict which patients with AP will develop severe symptoms [7]. Scoring systems and imaging methods may not provide sufficient information to determine the severity of AP, other parameters are needed [5]. Therefore, the search for effective biomarkers in the diagnosis of AP continues.
Inflammation plays an important role in the pathophysiology of AP [8]. Endocan is a molecule involved in inflammation [2]. Therefore, we thought that endocan may be important in the diagnosis of AP. There is a limited number of studies investigating the relationship of endocan with acute pancreatitis. Baykan et al. reported in a study they conducted that serum endocan level can be diagnostic in patients with pancreatitis. [9]. In this study, serum endocan levels were found to be significantly higher in AP patients compared to the control group. This finding supports the findings of Baykan et al. However, when the AP patient and control group were compared with the ROC analysis, it was seen that endocan was not strong enough to diagnose. The sensitivity (57.14%) and specificity (69.39%) of endocan were found to be low. We think that the difference between these two studies is due to the grouping of the patients. Since, although Baykan et al. evaluated AP by dividing it into subgroups, we compared all AP patients with the control group without grouping them.
Depending on the degree of pancreatic damage and the severity of the organism’s response, hepatocytes are stimulated by cytokines (IL-1 and IL-6) [4]. Accordingly, the acute phase response and the serum CRP level increase, which is the most important result of this response [10]. A serum CRP level above 150 mg/L is considered an indicator of poor prognosis [11]. The major disadvantage is that this increase in CRP peaks at 72 hours after the onset of symptoms [5]. However, CRP elevation in the first 48 hours is widely used because it is an inexpensive and reliable test that can determine disease intensity [5]. It has been reported that CRP>150 mg/L (sensitivity 80% specificity 76%) in the first 48 hours can distinguish severe AP [5, 12]. In this study, the CRP cut-off value was found to be >23.95 mg/L in the diagnosis of AP. The sensitivity (100%) and specificity (93.88%) of CRP in AP were found to be high enough to make a diagnosis. The reason for the difference between the findings obtained in this study and the previously reported findings for the CRP cut-off value is believed to be related to patient grouping. In this study, CRP data were analyzed without dividing the AP patient group into subgroups (mild, moderate, and severe AP), which is thought to be lower [12].
Immature granulocyte cells consist of promyelocyte, myelocytes, metamyelocytes and are not normally present in peripheral blood [13]. Studies show that IG can be used as an inflammation marker in the early period in the presence of inflammation [13]. More studies have been carried out recently on this parameter, which has not yet been used enough by clinicians.
The percentage of immature granulocyte (IG%) is a new inflammation marker that can be easily seen in a full blood count and is known to very few clinicians [3, 14]. Recent studies have shown that IG% relapses in the early stages of inflammation much earlier than traditional parameters such as CRP and white blood cells [3]. In the studies, it was determined that IG% of the patients in acute pancreatitis had a relapse related to the severity of the disease [3, 14]. Bedel et al. compared IG% in patients with moderate and severe AP and reported that the IG% was higher in patients with severe AP [3]. In this study, they reported that the IG% sensitivity was low in the diagnosis of severe AP. In this study, we found that the sensitivity and specificity of IG% were too low to be used in the diagnosis of AP [3]. On the other hand, Unal et al. reported that IG% can be used in the diagnosis of acute necrotizing pancreatitis in their study by dividing AP patients into subgroups. [15]. Ünal et al. focused on patients with acute necrotizing pancreatitis. In this study, we analyzed AP patients without subgrouping them. In this way, we think that it is important in terms of revealing the general situation of IG% in AP.
Conclusion
In this study, the role of endocan in the diagnosis of AP was investigated for the first time. Endocan was not found to be a strong enough biomarker for the diagnosis of AP. Likewise, it was found that IG% was not effective in the diagnosis of AP. On the other hand, it has been seen that CRP can be used in the diagnosis of AP, as many researchers have previously reported.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. Balta S, Balta I, Mikhailidis DP. Endocan: a new marker of endothelial function. Curr Opin Cardiol. 2021;36(4):462-8. DOI: 10.1097/HCO.0000000000000867.
3. Bedel C, Korkut M, Selvi F. New markers in predicting the severity of acute pancreatitis in the emergency department: Immature granulocyte count and percentage. J Postgrad Med. 2021; 67(1):7-11. DOI: 10.4103/jpgm.JPGM_784_20
4. Del Giudice M, Gangestad SW. Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters. Brain Behav Immun. 2018; 70:61-75. DOI: 10.1016/j.bbi.2018.02.013
5. Otsuki M, Takeda K, Matsuno S, Kihara Y, Koizumi M, Hirota M, et al. Criteria for the diagnosis and severity stratification of acute pancreatitis. World J Gastroenterol.
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10. Dambrauskas Z, Gulbinas A, Pundzius J, Barauskas G. Value of routine clinical tests in predicting the development of infected pancreatic necrosis in severe acute pancreatitis. Scand J Gastroenterol. 2007; 42(10):1256-64. DOI: 10.1080/00365520701391613
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Esat Taylan Ugurlu, Tulin Yazici, Ugur Fahri Yurekli. The role of endocan and immature granulocyte in the diagnosis of acute pancreatitis. Ann Clin Anal Med 2022;13(Suppl. 2):S76-79
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Investigation of the effect of anesthesia type on thiol-disulfide level in cord blood
Ozgul Ozgan Celikel 1, Gamze Gok 2, Ozcan Erel 2, Filiz Yildirim 3
1 Department of Obstetrics and Gynecology, Lokman Hekim University Hospital, 2 Department of Medicine Biochemistry, Ankara City Hospital, 3 Department of Internal Medicine, Polatlı Duatepe State Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21346 Received: 2022-08-06 Accepted: 2022-09-12 Published Online: 2022-09-28 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S80-84
Corresponding Author: Filiz Yildirim, Department of Internal Medicine, Polatlı Duatepe State Hospital, 06900, Ankara, Turkey. E-mail: drfyildirim@yahoo.com P: +90 544 411 2289 F: +90 312 243 10 12 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6151-2697
Aim: Oxidation and modifications of thiols are considered to be associated with diseases in a way that reveals the cause of some pathological events. It has been demonstrated that changes in analyzed thiol values can be studied as diagnostic or prognostic determinants for various pathologies.
Our study aimed to evaluate the possible changes in thiol-disulfide levels according to the type of anesthesia in patients who underwent cesarean section.
Material and Methods: In the present study, thiol/disulfide levels were measured in the venous blood and cord blood of 41 patients who had general anesthesia and 49 patients who had a cesarean section with spinal anesthesia before and after anesthesia. The correlation between native thiol, total thiol, disulfide, index 1, 2 and 3 levels in the samples collected by the anesthesia method was evaluated.
Results: As a result of the Repeated Measures Analysis of Variance, statistically significant differences were found in the pre- and post-anesthesia venous blood and cord blood measurements of the pregnant women who received both anesthesia in terms of native thiol, total thiol, disulfide, index 1, 2 and 3 variables (p<0.05).
Discussion: No significant difference between cord blood thiol/disulfide hemostasis values due to both anesthesia methods was detected. Besides, the difference between the thiol/disulfide pair values in venous blood samples from pregnant women and cord blood samples does not indicate an oxidant status. The results indicate that anesthesia is safe in terms of its potential to cause oxidant damage.
Keywords: Cesarean, General Anesthesia, Spinal Anesthesia, Thiol Disulfide Level, Cord Blood
Introduction
The oxidative effects of reactive oxygen species (ROS) are neutralized by the antioxidant capacity of the cells; thus, homeostasis is maintained. Cysteine (Cys) and its disulfide form, cystine (CySS), form the major low molecular weight thiol/disulfide pair in human plasma. Cys/Cyss pool is a critical redox control center in cellular communication [1].
Organic compounds containing a sulfhydryl group in their structure consist of sulfur and hydrogen atoms and are called thiols (SH). The -SH groups of thiols make them sensitive to oxidation, due to these properties, they protect the organism from oxidant damage as they are easily oxidized when they encounter oxidizing agents. Disulfides (-SS-) are a class of dynamic, redox-sensitive covalent bonds formed between two thiol groups [2]. The general thiol pool, composed of the sum of the individual amounts of small compounds such as cysteine, peptides such as glutathione, and thiol proteins such as thioredoxin (Trx) is found at variable oxidation/reduction ratios that are not in equilibrium [3].
Dynamic thiol-disulfide homeostasis (TDH) is an important parameter associated with various biochemical processes, including regulation of protein function, stabilization of protein structure, protection of proteins against irreversible oxidation of cysteine residues, chaperone function, regulation of enzyme functions, and transcription [4].
It is considered that the oxidation and modification numbers of thiols change in a way that reveals the cause of the pathological events existing in some diseases [3]. In fact, the plasma pools of CyS/CySS and GSH/GSSG vary depending on different conditions. It has been demonstrated that the values of redox potentials become more positive (oxidized) with age. GSH/GSSG plasma ratios vary as a result of oxidation at a rate of 0.7 mV/years in all ages between 18 and 93 years [5]. Besides, severe oxidizing thiol/disulfide redox reactions have been shown to arise in many conditions such as chronic alcohol abuse [6], high-dose chemotherapy, type 2 diabetes, and smoking [7]. During the oxidizing reactions, oxygen enters the bond between sulfides in disulfides, causing the bond to break down and the formation of two cysteines called thiols. The thiol oxidation load measured in plasma is often considered to represent plasma oxidative stress resulting from localized or systemic diseases [3]. Thus, increases in measured disulfide values are indicative of an oxidant medium and could potentially be studied as diagnostic or prognostic markers for various pathologies [5, 8].
In the light of all these data, it has been evaluated that there may be a change in thiol/disulfide values due to anesthesia in patients and their babies who are delivered by cesarean section, and that this change may even occur at different rates according to the anesthesia method. This study was designed to reveal the oxidation processes that may occur due to anesthesia or depending on the type of anesthesia and to evaluate the potential of their use as a possible prognostic marker.
Material and Methods
Subjects and collection of blood samples
The study was approved by the Ethics Committee of Yıldırım Beyazıt University, Yenimahalle Education and Research Hospital (Number: 2016/18). The study was conducted by taking cord blood samples of 90 randomly selected pregnant women aged 18-45 who had undergone a cesarean delivery. General anesthesia was applied to 41 of the patients, and spinal anesthesia was applied to 49 of them. Cord blood samples were taken from each pregnant woman in EDTA tubes before and after anesthesia.
Biochemical analyses
A technique in which 5,5’-dithiobis-(2-nitrobenzoic) acid (DTNB) namely Ellman’s reagent, which takes place as a chromogen, has been used so far to measure thiol levels [9]. Erel and Neselioğlu [10] have modified Ellman’s method. This new method evaluates both thiol and disulfide levels in the blood.
In our study, disulfide levels, disulfide/NT, and disulfide/TT ratios, NT/TT levels were analyzed in pregnant venous blood before and after general and spinal anesthesia and in cord blood.
Statistical analysis
The data were analyzed using the SPSS 23 package software. While evaluating the study data, frequencies (number, percentage) were given for categorical variables, and descriptive statistics (mean, standard deviation) were given for numerical variables.
The normality assumption of the numeric variables according to the groups was examined with the Shapiro-Wilk test of normality, and it was seen that they were distributed normally. For this reason, parametric statistical methods were used in the study.
Relationships between the two independent categorical variables were interpreted with the Chi-square analysis. Differences between two independent groups were analyzed with the Independent Sample T-Test. Differences between more than two dependent numerical measurements were checked using Repeated Measures Analysis of Variance. The statistical significance limit was (p value) accepted as 0.05.
Results
As a result of the independent sample t-tests applied, there was no statistically significant difference between the groups that underwent general anesthesia and spinal anesthesia in terms of the variables of gravid gestational week, BMI and birth weight of the baby (p>0.05). There was a statistically significant difference in terms of age (p<0.05). Accordingly, the mean age in the general anesthesia group was significantly higher than that of the spinal anesthesia group. As a result of the applied chi-square analysis, there was no statistically significant relationship between anesthesia groups and baby gender (p>0.05).
As a result of the applied independent sample t-tests, a statistical difference was found between the groups that underwent general anesthesia and spinal anesthesia in terms of hemoglobin and albumin values (p>0.05). Before and after both types of anesthesia maternal venous blood NT and cord blood NT; no statistical difference was found in maternal venous blood TT and cord blood TT values before and after both anesthesia types (p>0.05). No statistical difference was found in terms of maternal venous blood disulfide levels and cord blood disulfide levels before and after both types of anesthesia (p>0.05). No statistically significant difference was found in terms of maternal venous blood index 1 values and cord blood index 1 values before and after both anesthesia types (p>0.05). No statistically significant difference was found in terms of maternal venous blood index 2 values and cord blood index 2 values before and after both anesthesia types. Lastly, no statistically significant difference was found in terms of maternal venous blood index 3 values and cord blood index 3 values before and after both types of anesthesia (p>0.05).
As a result of the applied Repeated Measures Analysis of Variance, statistically significant differences were found between the venous blood and cord blood measurements of the mothers who received general anesthesia before and after anesthesia in terms of NT. TT disulfide index 1, index 2, and index 3 variables (p<0.05). Cord blood NT levels in the general anesthesia group were significantly higher than venous NT levels after anesthesia. Cord blood TT levels in the general anesthesia group were significantly higher than venous TT levels after anesthesia. Cord blood disulfide levels were significantly lower than venous disulfide levels before and after anesthesia in the general anesthesia group. Cord blood index 1 levels were significantly lower than pre-anesthesia venous index 1 levels in the general anesthesia group. Cord blood index 2 levels were significantly lower than venous index 2 levels before and after anesthesia in the general anesthesia group. Cord blood index 3 levels were significantly higher than venous index 3 levels before and after anesthesia in the general anesthesia group.
As a result of Repeated Measures Analysis of Variance, statistically significant differences were found in the spinal anesthesia group in terms of NT, TT, disulfide, index 1,index 2, and index 3 variables in the venous blood and cord blood samples before and after anesthesia (p<0.05). Accordingly cord blood NT levels were significantly higher than venous blood NT levels before and after anesthesia in the spinal anesthesia group. Cord blood TT levels in spinal anesthesia group were significantly higher than venous blood TT levels after anesthesia. Cord blood disulfide levels were significantly lower than venous blood disulfide levels before and after anesthesia in the spinal anesthesia group. Cord blood index 1 levels were significantly lower than venous blood index 1 levels before and after anesthesia in the spinal anesthesia group. Cord blood index 2 levels were significantly lower than venous blood index 2 levels before and after anesthesia in the spinal anesthesia group. Cord blood index 3 levels were significantly higher than venous blood index 3 levels before and after anesthesia in the spinal anesthesia groups (Figures 1, 2, and 3).
Discussion
One of the main purposes of many scientific studies performed is to reveal the markers that will show the prognosis of the diseases and will serve as diagnostic criteria. Likewise, a significant number of studies have been conducted on the possible association of various pathological conditions and their use as a potential oxidative marker by analysis of thiol and disulfide molecules [11, 12]. In this study we examined whether there were significant changes in thiol disulfide values in the venous blood and cord blood of patients who delivered by cesarean section depending upon anesthesia. In fact, we formed our study groups in this direction considering that this change may occur at different rates according to the anesthesia method. We aimed to reveal the oxidation processes that may occur due to anesthesia or depending on the type of anesthesia and to evaluate their use as potential prognostic markers.
During the oxidizing reactions that occur due to the formation of free radicals in tissues. A disulfide molecule is formed from two thiol (cysteine) molecules by establishing bonds between thiol molecules. The amount of thiol molecules after oxidation decreases after conversion of disulfide. The change in favor of an increase in the amount of disulfide in the thiol/disulfide redox couple is an indication of the presence of free oxygen radicals in the medium and that antioxidant defense works against them [3].
Scientific studies have shown that the thiol/disulfide pool changes in favor of disulfide due to oxidation damage in many pathological conditions [13]. In our study, we found that cord blood NT and TT values of pregnant women were higher when compared to venous blood values in both anesthesia groups. On the contrary, we found that the disulfide values decreased. When cord blood is taken as a reference, in the first place, maternal venous blood is used with high disulfide ratios, which is significant in terms of oxidation indicating that pregnant women are affected by anesthesia. However, venous blood values collected from pregnant women were collected both before and after anesthesia. Therefore, the fact that there was no significant difference between the values of pregnant venous blood taken after anesthesia and pregnant venous blood taken after anesthesia indicates that pregnant women did not suffer any oxidant damage due to anesthesia. However, NT and TT values in the cord blood of the baby, which was in a separate compartment from the maternal venous blood due to the placental barrier, were statistically higher than the NT and TT values in the maternal venous blood. This significant increase in cord blood samples, which is an example of post-anesthesia indicates that the baby was not exposed to an oxidant reaction due to anesthesia. This situation was found in the same way in both types of anesthesia (general and spinal anesthesia). Since the conversion of thiol groups to disulfides as a result of oxidant reactions requires a decrease in thiols, disulfides increase like a seesaw. However, the results of the study showed the opposite change. In parallel with this, the fact that index 1 values, which is the ratio of disulfide values to NT values and index 2 values, which is the ratio of disulfide values to TT values are found to be significantly decreased, indicates that the amounts of NT and TT do not participate in the formation of disulfide, that is to say they do not undergo oxidation. Besides index 3 values, which is the ratio of NT values to TT values, were found to be significantly increased. This showed that native thiols, which are sensitive to oxidation maintain their position in the total thiol pool. In previous studies, thiol values were found to be significantly higher than disulfide values according to cord blood measurements in cesarean deliveries [14]. These results contradict our results. However, the results in this contradicting study were evaluated not in terms of anesthesia and type of anesthesia but in terms of normal or cesarean delivery. In another study, postoperative cord blood samples from pregnant women who delivered by cesarean section were evaluated in terms of general and spinal anesthesia [15]. In this study, it was shown that the cord blood oxidation levels of pregnant women who received general anesthesia were higher than those who received spinal anesthesia based on increased disulfide values in cord blood samples from pregnant women. The results of this research also contradict the results of our research. However, since the results obtained in this study were obtained only between two types of anesthesia, this does not clearly prove that the results obtained are actually the increased oxidant level due to anesthesia because there was no reference cord blood values obtained from pregnant women who had a normal delivery without anesthesia in the study, and the evaluation was made only between anesthesia groups. If the cord blood values of pregnant women who had a normal delivery could be checked, the effects of anesthesia could be fully revealed according to the values to be obtained and we would be able to decide whether this contradicts our study or not.
On the other hand, the fact that babies are protected from possible oxidant stress despite the anesthesia applied to pregnant women can be attributed to the placental barrier. However, studies including cord blood thiol/disulfide analyzes have shown that infants suffer oxidant damage in pathologies belong to their mother [16]. This makes us think that the oxidation parameters within the normal limits in the cord blood we found in our study are not a result of the placental barrier.
Another result we obtained in our study is that the NT and TT levels in the venous blood of pregnant women are lower than the cord blood values representing the infants’ blood. The NT and TT values in an elderly mother are lower than the values of the baby who is at the beginning of his/her life and this indicates a decrease due to oxidative events experienced over the years. The results of our study have parallelism with the studies showing that the thiol/disulfide pool decreases with each year of life with age [5, 17].
Conclusion
When oxidant status was evaluated in terms of thiol/disulfide couples in the study, it has been demonstrated that general and spinal anesthesia applications did not create oxidative stress in both pregnant women and babies. This indicates that both types of anesthesia are safe methods for babies including pregnant women in terms of oxidant damage. On the other hand, a similar study can be planned so that an evaluation in this direction covers all redox mechanisms. Thus, the oxidant results of the anesthesia used for cesarean section in pregnant women and especially babies will be clearer and more precise.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328.ACAM.21346
Ozgul Ozgan Celikel, Gamze Gok, Ozcan Erel, Filiz Yildirim. Investigation of the effect of anesthesia type on thiol-disulfide level in cord blood. Ann Clin Anal Med 2022;13(Suppl. 2):S80-84
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The relationship of lactate clearance with mortality in COVID-19 pneumonia
Osman Sezer Çınaroğlu, Mehmet Göktuğ Efgan, Umut Payza
Department of Emergency Medicine, Katip Celebi University, Ataturk Research and Training Hospital, İzmir, Turkey
DOI: 10.4328/ACAM.21361 Received: 2022-08-16 Accepted: 2022-09-21 Published Online: 2022-09-28 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S85-88
Corresponding Author: Osman Sezer Çınaroğlu, Department of Emergency Medicine, Katip Celebi University, Ataturk Research and Training Hospital, Karabağlar, 35360, İzmir, Turkey. E-mail: drsezer@hotmail.com P: +90 232 243 43 43 / +90 507 386 12 34 F: +90 232 243 15 30 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3860-2053
Aim: In our study, we investigated the relationship of lactate clearance with disease severity and predictive mortality in patients with COVID-19 infection, which can lead to high mortality such as acute respiratory distress syndrome.
Material and Methods: The vital signs, demographic data and laboratory results of the patients who were diagnosed with COVID-19 pneumonia according to the results of CT and PCR analysis were recorded in the patient forms. Hospitalization status, intensive care requirements and disease outcomes of the patients were noted. Lactate clearance was calculated with the values at the time of admission to the emergency department and at the 6th hour. Data analyzes were performed in terms of the need for intensive care and its power to predict mortality.
Results: Data from 439 patients were analyzed for the study, and data from 318 patients who met the inclusion criteria were analyzed. The ROC analysis was performed to determine the value of lactate clearance in demonstrating mortality. When the areas under the curve were examined to test the power of LC in predicting survival, it was observed that the sensitivity was 82.76% and 75.69%.
Discussion: In our study, the power of LC to predict survival according to the severity of the infection in people with COVID-19 infection was examined and it was observed that it could significantly predict survival, especially in patients hospitalized in the intensive care unit. Therefore, this method, which is easy to apply, reproducible, non-invasive and cost-effective, can be recommended to predict the prognosis in patients with COVID-19 infection.
Keywords: COVID-19, Mortality, Lactate Clearance
Introduction
On March 11, 2020, the World Health Organization declared the COVID-19 infection caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) as a pandemic (available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10). COVID-19 infection may progress asymptomatically or cause mortality by causing acute respiratory distress syndrome (ARDS) [1]. The pandemic has been partially brought under control thanks to increased personal protection measures and widespread vaccination. On the other hand, the emergence of new variants of the virus makes it difficult to completely control the pandemic.
While some of the COVID-19- infected patients are being treated at home, some of them are being treated in wards and intensive care units according to their clinical status. The vast majority of hospital admissions due to COVID-19 are carried out by emergency services. This situation has created a huge burden on the emergency services. Critical patient management in the emergency department is a complex and dynamic process, as in other units. It is necessary to quickly grasp the clinical condition of the patient and to initiate serial intervention. Therefore, there is a need for easily calculable risk markers that can predict disease severity and provide patient triage in a short time.
Lactate is formed as a result of the reduction of pyruvate in the human body by the enzyme lactate dehydrogenase [2]. In a healthy person, the plasma lactate level is less than 2 mmol/L. In cases of hypoxia or hypoperfusion, plasma lactate level increases rapidly [3,4]. The concentration of lactate, which can be measured with a blood gas analyzer, is an easily measurable marker that shows the perfusion disorder of the tissues independently of blood pressure [5].
Many studies have shown that high serum lactate levels are associated with poor outcomes in patients with septic shock [6,7]. A high lactate value is a significant parameter in the estimation of mortality. However, lactate levels may be normal in some diseases that can be mortal. Therefore, there is a need for a more effective mortality indicator than the measurement of lactate alone in patients who require close follow-up, need aggressive treatment, and whose immediate metabolic status may vary. This has led to the investigation of the usability of lactate clearance rate, namely lactate clearance (LC), in critically ill care [3].
Therefore, in our study, we investigated the relationship of LC with disease severity and predicting mortality in patients with COVID-19 infection, which can lead to high mortality such as ARDS.
Material and Methods
Our study was designed as a retrospective and observational study. Patients who applied to the 3rd Stage University Hospital emergency service, which served as a pandemic center between March 2021 and March 2022, were included. Demographic characteristics, laboratory parameters and disease outcomes of patients with confirmed COVID-19 diagnosis in the emergency department were analyzed. The power of the data in predicting ICU admission and mortality was calculated.
The study included patients over the age of 18, who presented with symptoms suggestive of COVID-19 pneumonia, had a positive Polymerase Chain Reaction (PCR) test result, and had COVID-19 pneumonia confirmed by Computed Tomography (CT). Patients with comorbidities that may cause lactate elevation such as chronic liver disease, severe anemia, and severe dehydration symptoms in their medical history, patients with an active lung tumor and pulmonary edema, whose medical information could not be reached, or who had missing laboratory data were excluded from the study (Figure 1).
The data of the patients who met the study criteria were collected through the hospital information system. The vital signs, demographic data and laboratory results of the patients who were diagnosed with COVID-19 pneumonia according to the results of CT and PCR analysis were recorded in the patient forms. Hospitalization status, intensive care requirements and disease outcomes of the patients were noted. Lactate clearance was calculated with the values at the time of admission to the emergency department and at the 6th hour. Data analyzes were performed in terms of the need for intensive care and its power to predict mortality.
Approval for the study was granted by the Izmir Katip Celebi University Ethics Committee (no. 0287). The study conformed to the provisions of the 1995 Declaration of Helsinki.
Statistical analysis
Data were evaluated in IBM SPSS Statistics Standard Concurrent User V 26 (IBM Corp., Armonk, New York, USA), Medcalc and JASP statistical package programs. Descriptive statistics were given as x-(mean), ss (Standard Deviation) values. In addition, the homogeneity of variances, which is one of the prerequisites of the parametric tests, was checked with the Levene test. Normality assumption was checked with the “Shapiro-Wilk” test. In order to evaluate the differences between the two groups, the “Two Independent Samples t-test” was used. The “Roc Curve” analysis method was used to compare the diagnostic performances of two or more diagnostic or laboratory tests. When the relationship between two quantitative variables was required to be examined, the “Spearman rho” coefficient was used because the data did not meet the normal distribution conditions. The Chi-square test was used for the analysis of categorical data. A p-value of <0.05 was considered statistically significant.
Results
Data from 439 patients were analyzed for the study, and data from 318 patients who met the inclusion criteria were analyzed (Figure 1). Of the patients included in the study, 138 (43.4%) were female and 180 (56.6%) were male. The mean age of the patients was 72.57±14.54 years. The in-hospital mortality rate was 47.5%.
In the ROC analysis performed to determine the value of lactate clearance in demonstrating mortality, the area under the curve was found to be 0.573 (57.3%) for clearance and was statistically significant (p=0.023). The cut-off value for determining survival was accepted as ≤-38.89 (Table 1) (Figure 2). In the analyzes performed according to the clearance categories for mortality, the respiratory rate was found to be higher in the group with low clearance than in the group with higher clearance (p=0.021). Systolic blood pressure value was higher in the group with LC >-38.89 (p=0.026). SPO2 and PaO2 values were found to be statistically higher in the group with clearance ≤-38.89 (p=0.007, p=0.011, respectively). While the first lactate measurement was increased in the group with LC >-38.89 (p=0.003), the 6th-hour lactate value was also statistically higher in the LC ≤-38.89 group (p<0.001). Other variables did not differ statistically according to the cut-off value (p>0.05) (Table 2). When the data of all patients were included, a statistically significant negative correlation was observed between the respiratory rate, SPO2, PaO2, lactate 0 hours and lactate 6-hour values and clearance. No significant relationship was found in other variables (Table 3). When the areas under the curve were examined to test the power of LC in predicting survival, it was observed that the sensitivity was 82.76% and 75.69%, respectively, while the specificity was 32.4% and 37.21% in outpatients and ward patients (p=0.213, p=0.092, respectively). In terms of predicting survival in intensive care patients, the sensitivity was 40.56%, while the specificity was 76.88% (p=0.018) (Figure 3).
Discussion
In our study, the power of LC to predict survival according to the severity of the infection in people with COVID-19 infection was examined and it was observed that it could significantly predict survival, especially in patients hospitalized in the intensive care unit. Therefore, this method, which is easy to apply, reproducible, non-invasive and cost-effective, can be recommended to predict the prognosis in patients with COVID-19 infection.
The COVID-19 pandemic has started to lose its effect with vaccination, but has increased its momentum again recently due to the decrease in vaccination and the relaxation of social isolation measures. In parallel with this, patient admissions showing signs of COVID-19 such as fever, cough and respiratory distress have been increasing recently. For this reason, it is extremely important to identify and triage patients with poor prognosis in areas such as the emergency department, where the patient density is already high.
Recently, lactate level, decrease in follow-up lactate values and predictive aspect of mortality in different disease groups of LC have been investigated and it has been observed that it is a useful parameter. Reducing the lactate value is also recommended in recent guidelines and it is accepted that it is one of the important parameters of tissue perfusion improvement. On the other hand, the effect of LC on mortality has not been studied in patients with COVID-19 infection, which causes mortal conditions such as ARDS. COVID-19 infection is more mortal especially in elderly patients. The mean age of the patients in our study was 72 and the in-hospital mortality was 47.5%, which is consistent with this information.
The cut-off value of LC in terms of predicting mortality was 38.89. When the respiratory rate, SPO2, PaO2, lactate at 0 hours and 6th-hour lactate values are examined, a negative correlation with LC is observed. According to data obtained from other studies, survival is expected to increase in patients with high LC, and this negative correlation also supports the study hypothesis. In addition, the role of LC in predicting mortality was also examined in septic patients, and it was observed that it could predict survival in the septic shock patient group [8]. In another study by Marty et al. involving 91 intensive care unit patients with septic disease, it was observed that increasing LC by 20% significantly reduced 28-day mortality [9].
In another study emphasizing the importance of lactate in terms of reflecting mortality, 2 groups of patients were recruited. The target was to reduce the lactate value by more than 20% within 2 hours in one group, and achieve a central venous oxygen saturation of 70% in the other group. In the analyzes performed, it was observed that mortality was significantly lower in the group in which lactate was reduced [10]. In another study by Jansen et al., correction of LC and central venous oxygen saturation together reduced the mortality rate by 9.6% [10]. In our study, mortality in intensive care patients with high LC was lower and the power of LC to predict survival was significantly higher, which is in line with the literature.
The specificity of LC in predicting mortality in all diseases causing mortality was between 52-84%, and it was found to be 76% in our study [11]. Consistent with other causes of mortality, LC also predicts survival well in patients with COVID-19.
The most important limitation of our study is its single-center and retrospective design. The data of the patients were recorded considering their first application. These dynamic parameters are likely to vary according to disease severity and response to treatment. Although the results are reliable, multicenter clinical studies with more patients are needed.
Conclusion
The LC significantly reflects the probability of survival in patients with COVID-19 infection, especially during ICU admission. Since it is an easily applicable, inexpensive and reproducible test, it can be used as a useful parameter to predict the prognosis for people with COVID-19 infection in the emergency department.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Funding: None
Conflict of interest
The authors declare no conflicts of interest.
References
1. Zhou F, Yu T, Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–62.
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11. Zhang Z, Xu X, Chen K. Lactate clearance as a useful biomarker for the prediction of all-cause mortality in critically ill patients: a systematic review study protocol. BMJ Open. 2014; 4:e004752.
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Osman Sezer Çınaroğlu, Mehmet Göktuğ Efgan, Umut Payza. The relationship of lactate clearance with mortality in COVID-19 pneumonia. Ann Clin Anal Med 2022;13(Suppl. 2):S85-88
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Evaluation of quality of life and depressive symptoms in patients receiving dialysis
Mehmet Yilmaz Salman 1, Hilal Arslan Akgul 2
1 Department of Urology, 2 Department of Psychiatry, Sancaktepe Prof Dr Ilhan Varank Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21371 Received: 2022-08-27 Accepted: 2022-09-27 Published Online: 2022-10-19 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S89-92
Corresponding Author: Department of Urology, Sancaktepe Prof Dr Ilhan Varank Training and Research Hospital, Sarıgazi Emek, Namık Kemal Cd. No 54, 34785, Sancaktepe, Istanbul, Turkey. E-mail: mdmehmetyilmazsalman@yahoo.com P: +90 216 606 33 00 / 532 723 47 78 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9996-2300
Aim: End- stage renal disease (ESRD) is defined as a progressive loss of renal function that becomes life-threatening, impacting the daily life of affected people and their family members. The objective of this study was to evaluate the psychiatric symptoms and general health status of ESRD patients receiving regular hemodialysis treatment in a particular center.
Material and Methods: All patients receiving regular hemodialysis due to end-stage renal disease (ESRD) in the Tirebolu district of Giresun province, Turkey were examined. Age, gender, body mass index, time elapsed since the first dialysis and urine output were questioned and recorded by interviewing the patients face to face. Psychiatric symptoms of the patients were evaluated using SCL-90-R scale and overall quality of life using SF-36 scale.
Results: A total of 33 patients receiving dialysis were included in the study. Depressive symptoms were found in 18% of the patients and phobic anxiety in 12.1%. The physical distress caused by dialysis was found as 30%, and the somatization level was 8%. There was a significant decrease in physical function and strength, especially in women. Accordingly, while the mean SCL-90 score of those with no urine output was 1.44±0.73, it was 0.77±0.52 for those with urine output, which was almost half (p=0.008).
Discussion: Patients receiving hemodialysis treatment for ESRD are found to have psychiatric symptoms as well as physical distress. Psychiatric and physical symptoms impair quality of life. Women suffer more from pain than men and their quality of life is worse. Having urine output provides mental and physical well-being.
Keywords: ESRD, Quality of Life, SCL-90, SF-36, Pain, Urinary Output
Introduction
End stage renal disease (ESRD) is defined as a progressive loss of renal function that becomes a life-threatening and debilitating chronic illness impacting the daily life of affected people and their family members [1]. The development of chronic kidney disease (CKD) and its progression is still a significant source of decreased quality of life and significant premature mortality [2]. As in the world, the number of patients with end-stage renal disease (ESRD) is increasing in Turkey and the number of patients receiving renal replacement therapy reached 83,783 as of 2019 [3].
Any disturbance in the human body can cause emotional, psychological and social reactions. Anxiety about the deterioration of bodily integrity, threat of death and even involuntary changes in routine diet can cause an emotional and psychological collapse [4]. The quality of life in ESRD patients is worse than in the normal population [5]. Although physical symptoms are thought to be the main determinant in the decrease in quality of life, major depression is also an important factor [6]. Psychiatric symptoms seen in dialysis patients are directly related to physical disorders and reduce patients’ quality of life [7].
The loss of urination and renal function can lead to a strong emotional crisis in the patient. Although dialysis can significantly prolong a patient survival, it can replace only a small portion of normal physiological function of the kidney, and underlying disease is not cured by dialysis [8]. It has been reported that the patient undergoing dialysis is in an unusual existence, because the patient’s dependent state is a source of serious discomfort [9]. Patients with ESRD on dialysis suffer from a burden of psychiatric symptoms because of the disease itself, its treatment or comorbid conditions. This condition is also associated with an increased risk of future hospitalization and mortality, underlining the need for early interventions [10]. Nevertheless, symptom burden amongst patients undergoing dialysis is often underrecognized [11]. It is therefore important to measure the quality of life in these patients through universally recognized scales for early recognition of psychiatric symptoms encountered by these patients and to take necessary measures, if necessary. The objective of this study was to evaluate the psychiatric symptoms and general health status of ESRD patients receiving regular hemodialysis treatment in a particular center.
Material and Methods
Before the beginning, the study protocol was approved by the local ethics committee of our hospital. All patients were informed about the objective of the study and gave written informed consent. The study was conducted in accordance with the relevant ethical principles of the Declaration of Helsinki revised in 2013.
All patients receiving regular hemodialysis due to ESRD in the Tirebolu district of Giresun province, Turkey were examined. The age, gender, body mass index, time elapsed since the first dialysis and urine output were questioned and recorded by interviewing the patients face to face. Since the education level of the patients was mostly primary school or below, no classification was made according to education level. According to the income level, patients were divided into two groups as those with an income at or below the minimum wage and those with a higher income. Psychiatric symptoms of the patients were evaluated using SCL-90-R scale and overall quality of life using SF-36 scale.
SCL-90-R Scale
Symptom Checklist-90-Revised (SCL-90-R) is a widely used survey tool developed by Leonard R. Derogatis to determine a number of psychological symptoms [12]. SCL-90-R includes 90 symptoms and evaluates nine symptomatic dimensions including: somatization, obsessive-compulsive disorder, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. Additional items include sleep, appetite disturbance, and guilt. According to the answers given to the questions, each question was given 1-4 points, “none” or “no” answer was not scored. The resulting total score was “total positive symptom”; while “general symptom level” was found by dividing the sum of the scores obtained by the total number of questions answered.
SF-36 Scale
The SF-36 is widely used to measure health status or quality of life (QOL) in both healthy and sick populations. SF-36 consists of seven subdimensions including physical functioning, role limitations due to physical and emotional problems, mental health, general health perception, bodily pain, social functioning, and vitality. Scores for the different domains are converted and pooled using a scoring key, for a total score indicating a range of low to high QOL. Validity and reliability of the Turkish version of Short form 36 has been widely studied for use in different diseases [13]. Reliability and construct validity of the SF-36 in Turkish cancer patients was studied by Pinar [14]. By examining the data obtained from the patients, the health status and the factors affecting the health status were investigated.
Statistical Analysis
Data obtained in this study were statistically analyzed using the SPSS (SPSS, Social Package for Social Sciences, IBM Inc., Chicago, IL, USA) software. The normality of the data was tested using the Shapiro-Wilk method. Pearson’s Chi-square test was used in the comparison of non-parametric variables, Pearson’s correlation test for determining correlation between the variables, and the Mann-Whitney U test for the comparison of non-normally distributed variables. Continuous variables are expressed as mean±standard deviation, minimum and maximum values and categorical variables as numbers and percentages. P<0.05 values were considered statistically significant.
Results
A total of 33 patients receiving dialysis were included in the study. The mean age of the patients was found as 62.6±15.5 (28-87) years. Of all patients, 15 (45.45%) were female and 18 (54.55%) were male. The mean body mass index (BMI) was calculated as 23.5±3.54 (17.5-31.6) Kg/m2. The demographic and basic data of the patients are shown in Table 1.
When the SCL-90 form scores were examined, it was seen that the mental problems were not at a level to cause psychoticism and paranoid pathology. However, depressive symptoms were found in 18% of the patients and phobic anxiety in 12.1%. The physical distress caused by dialysis was found as 30%, and the somatization level as 8% (Table 2).
When the results of the SF-36 form were examined, there was a significant decrease in physical function and strength, especially in women. While pain is an important problem in women, it has been observed that it does not pose a problem in men. General health perception and vitality were similar in men and women, which is lower than in the normal population. It was observed that both groups were affected emotionally, but women were more affected. Mental health does not appear to have been affected. As a result, social functioning continued in both groups, which is not different from healthy individuals (Table 3).
No correlation was found between the income status of the patients and their SCL-90 and SF-36 scores or subgroup scores. No significant difference was found between time since the first dialysis and SCL-90 and SF-36 scores or subgroup scores. Two or three dialysis sessions a week had no effect on SCL-90 and SF-36 scores.
There was a significant difference in the additional items in the form of SCL-90 in patients with urine output compared to those without. Accordingly, while the mean score of those with no urine output was 1.44±0.73, it was 0.77±0.52 for those with urine output, which was almost half (p=0.008). The emotional role score in the SF-36 form was 33.3±19.9 in those without urine output, and 45.3±13.7 in those with urine output (p=0.033).
Discussion
There are very limited data available regarding the quality of life (QoL) of patients with ESRD maintained on dialysis in the developing world. In the present study, we investigated the effect of receiving dialysis on patients’ quality of life.
The psychological and emotional effects of dialysis negatively affect daily physical activities [15]. The complete end of the kidneys’ function and the replacement of life with dialysis causes an alienation in patients from their own body structures and functioning [7]. QoL in ESRD patients can affect their individuality in disease or improvement, but yet, the predictive role of QoL for improvement in CRF is still uncertain [16]. If these feelings of indecision about life concepts are not adequately answered, they lead to feelings of aggression and anger, and this can lead to social disengagement and even self-harm. In the present study, nearly one in five patients had signs of major depression and 30% of patients had physical distress. In the results of the SF-36 form, the most serious difference compared to the normal population was seen in physical function and limitations due to physical problems.
De Pasquale et al. reported that physical and mental distress scores were closely correlated in dialysis patients [7]. The adaptation to the ESRD features, knowing that it has no cure and treatment is highly complex, also means adapting to the numerous changes in quality of life, due to various symptoms in the course of the disease. Some of them cause different levels of physical limitation and functioning [17]. In a study, it was reported that the quality- of- life score did not change as the time passed since the first day of dialysis increased [18]. In another study, time since dialysis was associated with the QoL domains of physical health and work, but this was not significant in multivariate analysis [19]. In our study, it was observed that psychiatric and physical symptom scores did not increase linearly as the dialysis time increased.
The quality- of- life score is higher in males when all independent variables are excluded. In a study by Ismael et al. overall quality of life was higher among male dialysis patients, but the difference did not reach statistical significance (p=0.84) [20]. In this regard, the literature has revealed contradictory results. Rostami et al. stated that QoL was better in male than female patients [21], while Bayoumi et al. reported that female patients had a higher level of QoL than male patients [22]. In our study, the pain score was found to be significantly lower in women than in men. We found that the effect of pain on women was different from men, which may explain significant limitations due to physical functioning.
Urine output may continue in some patients with ESRD. It can be expected that the quality of life will be higher as those with urine output can take more daily fluids. We found that daily activities such as sleeping and eating were less troublesome in those with urine output. Likewise, we found that the emotional role score was higher in those with urine output. In a study by Shafi et al. ESRD patients with urinary output reported higher QoL scores [23]. This may be due to a wider dietary choice created by urine output and the well-being brought about by greater daily fluid intake. van der Borg et al. stated that dialysis patients felt themselves in a strange existential situation, which is due to the changing body functioning [24]. The most obvious part of the change in body functioning noticed by the patient may be the absence of urine output. This suggests that urine output not only provides physical relief, but also provides psychological well-being as it prevents deterioration in body image.
Study Limitation
The major limitations of this study include the relatively small number of patients and being conducted in one region. However, we tried to prevent regional differences among the patients by including the patients receiving continuous hemodialysis treatment in only one district in our study. Finally, a control group could be included. However, given limited studies on this issue especially in developing countries, we believe that our findings will be guiding for future studies.
Conclusion
Patients receiving hemodialysis treatment for ESRD have psychiatric symptoms as well as physical distress. Psychiatric and physical symptoms impair quality of life. Women suffer from pain more than men and their quality of life is worse. Having urine output provides mental and physical well-being.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328.ACAM.21371
Mehmet Yilmaz Salman, Hilal Arslan Akgul. Evaluation of quality of life and depressive symptoms in patients receiving dialysis. Ann Clin Anal Med 2022;13(Suppl. 2):S89-92
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The effect of radial shortening osteotomy and the level of osteotomy line on lunate vascularization in Kienböck’s disease
Tahsin Sami Çolak
Departmant of Orthopedics and Traumatology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21372 Received: 2022-08-28 Accepted: 2022-09-28 Published Online: 2022-10-11 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S93-96
Corresponding Author: Tahsin Sami Çolak, Departmant of Orthopedics and Traumatology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey. E-mail: drtahsincolak@gmail.com P: +90 530 037 37 36 F: +90 332 223 00 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7028-9397
Aim: The aim of this study is to show the intraosseous changes in the vascularity of the lunate with magnetic resonance imaging (MRI) after radial shortening osteotomy (RSO), which is an extra-articular intervention, as well as the effect of the osteotomy level on the vascularity of the lunate.
Material and Methods: Thirty-one patients with a diagnosis of Lichtman Stage II and IIIA Kienböck who underwent RSO were analyzed retrospectively. Among these patients, 17 patients who had both preoperative and postoperative MRIs were included in the study. The mean age of the patients was 34.2. (±12.25) years. Lunate vascularity was evaluated with diffusion MRI before and after surgery. In addition, the effect of osteotomy level on the blood supply of the lunate was also examined.
Results: It was observed that RSO had a positive effect on the vascularity of the lunate radiologically and clinically (94%). Especially in patients with osteotomy level between 20-24 mm, the increase in vascularity was more evident than in other patients.
Discussion: In this study, although clinical improvement was detected in the majority of patients (94%) after RSO, only 58.9% of the patients showed increased vascularity of lunate, suggesting that the osteotomy level has an effective role in increasing the vascularity to the lunate.
Keywords: Keinböck’s disease, Lunate, Radial Shortening Osteotomy, Revascularization
Introduction
The etiology of Kienböck’s disease is still controversial since Robert Kienböck first identified the disease [1]. Lunatum is at risk of osteonecrosis due to disruption of the venous flow network and limited collateral blood flow. In addition, the presence of negative ulnar variance accelerates the progression of the disease morphologically [2]. A number of treatment strategies have been described in the literature according to the stage of the disease [3-7].
At an early stage of the Keinböch disease treatment algorithm, decompressive methods are more recommended [6-7]. Especially in patients with negative ulnar variance in whom wrist arthrosis does not develop, radial shortening osteotomy (RSO) and radial closed-wedge osteotomy are suggested to prevent the worsening of the disease by reducing the force transmitted to the lunate. In the literature, it was reported that positive results were obtained clinically and radiologically [8-10]. Blanco et al. suggested that radial osteotomy alone even without shortening, could improve arterial blood flow and venous drainage in the wrist, and improve vascularity around the lunate and has good clinical results [11]. To the best of our knowledge, there is no study in the literature that evaluates correlation between the vascular changes in the lunate after RSO with the osteotomy level and demonstrates it radiologically with Magnetic Resonance Imaging (MRI). We think that determining the optimum osteotomy level will have a more positive effect on the blood supply of the lunate. The aim of this study is to reveal the intraosseous therapeutic effect of RSO applied as an extra-articular procedure on the vascularity of the lunate using MRI in Litchman Stage 2 and 3A Keinböch patients, and to investigate the effect of the osteotomy level on the vascularity of the lunate.
Material and Methods
In this study, 31 patients who underwent RSO for Stage 2 and 3A Kienböck’s disease in our clinic between January 2012 and January 2020 were retrospectively analyzed. Our study was performed with the approval of the hospital’s local ethics committee. Patients with pre- and postoperative MRI and clinical follow-up of more than 2 years were included in the study, while patients who did not meet these criteria or had other wrist pathology, had no union, and had additional wrist trauma were excluded from the study. The study included 17 patients who met the criteria. The mean age of the patients was 34.2 (18-53) years. Ten (58.8%) of these patients were male and 7 (41.2%) were female. Eight (47.1%) of these patients had stage 2 and 9 (52.9%) had stage 3A Keinböck disease. The mean follow-up time was 52.4 months (24-69). The mean negative ulnar variance was -1.8 mm (-3.4-1.0). Preoperative and postoperative MRIs were compared by an experienced independent radiologist, and vascular changes in the lunate bone were evaluated according to criteria established by Lee et al. (Table1). Radius osteotomy line levels were measured from the distal edge of the radial styloid at plain radiographs. The mean osteotomy level was calculated as 25 mm (17-58 mm). The amount of shortening was determined by calculating the negative ulnar variance preoperatively. The operations were performed by a single experienced surgeon. In the early postoperative period, the patients were followed up for 1 month using a splint. Wrist rehabilitation protocol was started after splint removal in all patients. Visual Analogue Scale (VAS) scores were recorded before and after surgery. In the follow-up, the clinical conditions of the patients were evaluated periodically by looking at the VAS score. In only one patient, the implants were removed voluntarily, although there was no additional complaint.
The data obtained from the research were transferred to the SPSS (Statistical Package for Social Sciences) v.18.0 package program for statistical analysis. The relationship between increased vascularity and VAS scores used in clinical evaluation was evaluated using correlation analysis. The t-test was used to compare preoperative and final follow-up measurements. P<0.05 was considered statistically significant.
Results
No complications (neurovascular injury, infection, nonunion) were observed in 17 patients during the follow-up. While clinical complaints were decreased in 94% (16/17) of the patients, an increase was observed in the complaints of 1 patient. The mean preoperative VAS score was 7.8 (6-9). The mean VAS score of the patients at the last follow-up was 2.3 (1-9) (Table 2). While significant increase in blood flow was observed in 10 (58.9%) patients, there was no increase in blood flow in 6 (35.2%) patients. Decreased lunate blood flow and increased disease stage and fragmentation were observed in 1 (5.9%) patient. In this patient, the osteotomy level was 58 mm. Although the increase in blood supply in the lunate was more prominent in patients with osteotomy level between 20-24 mm compared to other patients, no statistically significant difference was found (p=0.645) (Table 3). None of the patients developed lunate collapse or wrist arthrosis (Figure 1).
Discussion
In this study, although clinical improvement was detected in the vast majority of patients (94%) after RSO, only 58.9% of the patients had increased blood supply in lunate. In patients with osteotomy level of 20-24 mm, the increase in blood supply was more evident, but there was no statistically significant difference between the increase in blood supply and the osteotomy level (p=0.645). Although our obtained outcomes are consistent with similar literature data, we think that different studies should be done to determine the optimum osteotomy level that will increase the blood flow of the lunate.
RSO is generally preferred in the treatment of Lichtman Stage 2 and 3A disease [10,12]. The aim of RSO is to reduce the load on the lunate. In addition, theoretically, it is also aimed to increase the vascularization of the lunate. There are many studies investigating vascular changes in the lunate after RSO [13-15]. Nakamura et al. reported that as a result of a 3-year follow-up of 24 patients who underwent RSO or radial wedge osteotomy, there was an increase in signal in both T1 and T2 sequences on MRI in 79.2% (19/24) of the patients [13]. On the other hand, Matsui et al. showed increased vascularity of the lunate during at least 10 years of follow-up in 7 (70%) of 10 patients who underwent radial shortening osteotomy [15]. In our study, this rate was found to be 58.9% (10/17). In addition, studies demonstrating the success of radial osteotomy have hypothesized that even only radial osteotomy without shortening improves symptoms by changing the local vascular environment [11,16].
While investigating the effect of RSO on the vascularity of lunate, no study was found in the literature in which the optimum osteotomy level was determined. Our study is unique in terms of contribution to the literature, as we also evaluated the effect of osteotomy level on blood flow. Especially in all 10 patients (100%) with an osteotomy level of 20-24mm, both clinical complaints and radiological increase in blood flow were detected, suggesting that the osteotomy level is important in the healing process.
There are studies in the literature describing lunate revascularization after RSO radiologically. Various methods such as radiography, computed tomography (CT), and MRI have been usually used to evaluate radiographic results and increase in blood flow, after RSO [17-20]. Evaluation of the lunatum with simple radiographs is not sufficient to evaluate Kienböck’s disease after treatment. In this study, MRI was used to evaluate the vascularization status after RSO. Gadolinium (Gd)-MRI provides direct visualization of perfusion and is suitable for investigating the vascularity of the lunate [21]. Both preoperative and postoperative Gd-MRI showed significantly increased revascularization in the lunate in 10 (58.9%) of 17 patients. It was also observed that the perfused volume of the lunate increased significantly. This finding suggests that RSO induces an increase in vascularization as well as a decrease in the load on the lunate.
In addition to osteotomy, the absence of increase in blood supply despite shortening in all patients suggests that there are some other factors affecting blood supply. For example, Lunate types were not taken into account in the evaluation in this study. We think that different results may arise due to the fact that bone shapes with different anatomical features may affect the intraosseous pressure to which the lunate is exposed. Also, since we made the shortening amounts according to the negative ulnar variance, shortening was not performed at the same rate for each patient. We think that this situation may also affect our results.
The present study had several limitations. First, we used a retrospective method that limits the level of evidence. Secondly, the number of our patients was not sufficient to allow subgroup analysis in terms of parameters that may affect the results such as age, gender and smoking. However, as the number of cases increases, comparative studies with the control group who only underwent osteotomy without radial shortening may reveal the effect of shortening on blood supply more clearly.
Conclusion
The results of RSO performed in patients with negative ulnar variance in Stage 2 and Stage 3A Keinböch disease are clinically and radiologically satisfactory. The radiological increase in blood flow and the fact that the disease stage has not progressed, especially in all patients (100%) with an osteotomy level of 20-24 mm, shows that the osteotomy level has an important role in the healing process. However, it is obvious that multicenter clinical studies should be conducted to determine the optimum osteotomy level.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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3. Kirkeby L, von Varfalva Palffy L, Hansen TB. Long-term results after vascularised bone graft as treatment of Kienböck disease. J Plast Surg Hand Surg. 2014;48(1):21-3.
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6. Lichtman DM, Lesley NE, Simmons SP. The classification and treatment of Kienbock’s disease: the state of the art and a look at the future. J Hand Surg Eur Vol. 2010;35(7):549-54.
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Tahsin Sami Çolak. The effect of radial shortening osteotomy and the level of osteotomy line on lunate vascularization in Kienböck’s disease. Ann Clin Anal Med 2022;13(Suppl. 2):S93-96
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Genetic abnormalities in childhood acute lymphoblastic leukemia at Hue Central Hospital, Vietnam
Nguyen Thi Kim Hoa
Ph.D Student, Faculty of Medicine and Pharmacy, Hue University, Hue, Vietnam
DOI: 10.4328/ACAM.21373 Received: 2022-08-30 Accepted: 2022-09-30 Published Online: 2022-10-18 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S97-100
Corresponding Author: Nguyen Thi Kim Hoa, Ph.D Student, Faculty of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, Vietnam. E-mail: kimhoa.fmi@gmail.com P: +84 935 645836 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2525-4368
Aim: Acute lymphoblastic leukemia (ALL) is the most common malignant disease in children. Genetic abnormalities have been recognized to have prognostic or therapeutic relevance. In this study, we aimed to analyze the genetic abnormalities in childhood acute lymphoblastic leukemia patients which impact treatment and prognosis.
Material and Methods: It was a descriptive cross-sectional study on childhood acute lymphoblastic leukemia patients who admitted to the hospital between April 2018 and May 2022.
Results: There were 83 new patients, the male to female ratio was 1.37:1. The mean age was 5,18 ± 3,46 years. The most common symptoms were anemia (84.3%), fever (55.4%), hepatomegaly (53%), splenomegaly (45.8%), enlarged lymph nodes (45.8%), bleeding (34.9%) and bone pain (26.5%). Regarding laboratory features, 30.1% of the patients had white blood cell (WBC) ≥ 50×109/l, 74.5% of the patients had platelet (PLT) < 100×109/l, 90.3% of the patients had blood hemoglobin level (Hb) < 11 g/dl. Genetic analysis showed that 12.1% of patients have TEL/AML1, 4.8% of patients have BCR/ABL1, 3.6% of patients have E2A/PBX1, 2.4% of patients have MLL/AF4 and 1.2% of patients have SET/NUP214.
Discussion: The most common clinical presentations were anemia, fever, hepatosplenomegaly, bone pain and bleeding. Genetic abnormalities determine the prognosis and adjust the treatment for patients.
Keywords: Acute Lymphoblastic Leukemia, Children, Genetic Abnormalities
Introduction
Acute leukemia is the most common cancer in children and teenagers, accounting for 25% of all childhood cancers [1]. It is a disease of the hematopoietic system characterized by the uncontrolled proliferation of one or more malignant immature cell lines. In acute leukemia, acute lymphoblastic leukemia (ALL) accounts for about 75%. The disease can easily lead to early death if not diagnosed and treated promptly. The incidence of acute lymphoblastic leukemia is about 2-5 cases per 100,000 children and ALL is the most common in children aged 2-5 years.
In developed countries, over the past 30 years, the effectiveness of treatment for acute lymphoblastic leukemia is gradually improving, the 5-year disease-free survival rate after commencing treatment is 80% [2]. In the US, this rate is up to 95% [1]. The detection of gene mutations helps to diagnose accurately and improve treatment [1, 3].
Many prognostic genetic markers of acute lymphoblastic leukemia have been identified, including genetic hybridization (BCR/ABL1, TEL/AML1, E2A/PBX1, MLL/AF4) and (hyper/hypoploidy), immune phenotypes (such as T/B cell markers).
Therefore, I carried out this study to describe clinical and laboratory characteristics of childhood acute lymphoblastic leukemia, and identify some of the genetic changes in acute lymphoblastic leukemia.
Material and Methods
Patients
Eighty-three patients were diagnosed with ALL at Hue Pediatric Center- Hue Central Hospital from April 2018 to May 2022. All ethical regulations were followed, and this study was approved by the Hue Central Hospital Ethics Committee (Institutional Review Board No. 18/NCKH-BVH). Consent was obtained from all participants in this study.
Method
This is a descriptive cross-sectional study. We described clinical presentations, laboratory tests and genetic tests. Genetic tests were done with Hemavisio28N kits which was a multiplex-RT-PCR test.
The diagnosis of ALL on admission was made on the basis of bone marrow morphology, which showed more than 20% of leukemic blasts. According to the results of flow cytometry, acute lymphoblastic leukemia was diagnosed.
Data were analyzed according to age, gender, clinical presentations, laboratory tests, and genetic tests. All statistical analysis was performed using SPSS v.18.0 (IBM Corp, Armonk, NY).
Results
A total of 83 new patients with ALL were identified from April 2018 to May 2022 who met eligible criteria. Among these patients, 48 were males and 35 were females, the male to female ratio was 1.37:1. The mean age was 5,18 ± 3,46 years. The peak incidence of ALL occurred in the age group (1-< 10 years), accounting for 79.5% (Table 1). There were 59,0% of patients with standard risk, and 41,0% of patients with high risk. The percentages of B-ALL and T-ALL were 85.5% and 14.5%, respectively.
Regarding clinical presentations, the mean time from the onset of symptoms to the hospital admission was 23.0 ± 23.7 days. The most common symptoms were anemia (84.3%), fever (55.4%), hepatomegaly (53%), splenomegaly (45.8%), enlarged lymph nodes (45.8%), bleeding (34.9%) and bone pain (26.6%). There were two cases with testicular involvement (2.8%).
For laboratory features, 30.1% of the patients had white blood cell (WBC) ≥ 50×109/l, 74.5% patients had platelet (PLT) < 100×109/l, 90.3% patients had blood hemoglobin level (Hb) < 11 g/dl. The mean values of blast cells in the bone marrow and peripheral blood were 14 ± 18 % and 156,5 ± 21,5 %, respectively.
Regarding biochemical tests, renal failure at the time of admission accounts for a very small percentage (1.2%), and 37.5% of patients have elevated transaminase. Most patients had increased LDH (89.9%) and uric acid (79.7%) levels. Nearly ¼ of patients had CRP > 8 (27.1%). There were no patients with CNS involvement at the time of diagnosis.
In 32 cases with chromosomal testing, the percentage of abnormal chromosomal preparation was low, only 9.4% of children with hyperdiploid chromosomes and 3.1% of children with extra chromosomes (Table 2).
In gene testing on 83 ALL patients, there were 10 patients with TEL/AML1 fusion (12.1%), 4 patients with BCR/ABL1 fusion (4.8%), 3 patients with E2A/PBX1 fusion (3.6%), 2 patients had MLL/AF4 fusion (2.4%) and 1 patient had SET/NUP214 fusion (1.2%) (Table 3).
Discussion
The male/female ratio was 1.37:1 and the mean age was 5.18 ± 3.46 years, similar to some studies by Fadoo, Al-Sudairy and Yasmeen [4-6]. The highest rate was in the age group (1- <10 years old), accounting for 79.5%, similar to the reports in Pakistan and Saudi-Arabia [4, 5, 7]
The mean time from symptom onset to hospital admission was 23.0 ± 23.7 days (range 1-90 days). The period was shorter than Robazzi’s result [8], and longer than the result of some authors [4, 5]. The cause may be that the early symptoms of ALL resemble other common diseases, or the family’s economic difficulties, so parents could not bring their children to the hospital in time.
The most common symptom in our study group was anemia, accounting for 84.3%, followed by fever (55.4%), hepatomegaly (53%), splenomegaly (45.8%), lymphoadenopathy (45.8%). Other manifestations included: bone pain (26.5%), hemorrhage (34.9%), testicular infiltration (2.8%). The cause of these manifestations was explained by the proliferation of immature cells in the bone marrow, which crowded out the normal development of hematopoietic cell lines, leading to anemia and at the same time neutropenia leading to fever and easy infection. Subsequently, the immature cells infiltrated the organs in the body, leading to lymphadenopathy and hepatosplenomegaly. Fadoo et al in their study also showed similar clinical manifestations with almost similar frequency [4]. In our study results, the average temperature at admission was 37.8 ± 0.9 degrees, ranging within 37-40 degrees Celsius.
Regarding cell lineages, B-call lineage accounted for a high percentage (85.5%), and T-cell lineage accounted for 14.5%. The result was similar to the results of studies in developing countries. According to Fadoo, there were 78.5% of B-cell patients and 17.5% of T-cell patients. According to Al-Sudairy, there were 89.5% of pre-B cell patients and 10.5% of T-cell patients [4, 5].
Regarding peripheral blood, there were 30.1% of patients with white blood cell count ≥ 50×109/l, similar to the result of Fadoo’s study in Pakistan, with 28.8% [4], and higher than that of Pui (20%) [9], or 21.7% by Al-Sudairy [5]. Patients with elevated leukocytes are at risk for tumor lysis syndrome and have a poor prognosis [9]. Moreover, patients with elevated white blood cells often have elevated LDH levels [10]. It was notable in the white blood cell count that the neutrophil count was reduced, with a mean of 4.1 ± 11.3 x109/l. A low threshold of neutrophils is the cause of fever and infection in most patients, especially when chemotherapy begins. Regarding platelet count, there were 74.5% of patients with platelets < 100×109/l. Regarding hemoglobin level, there were 90.3% of patients with hemoglobin < 11g/dl.
When performing bone marrow aspiration, the result showed that the mean peripheral blood blast was 32.6 ± 29.1%, and the bone marrow showed the mean blast value of 61.6 ± 20.3%, fluctuating from 20 to 98%.
In terms of biochemical tests, the results of our study showed that one patient (1.2%) had a renal failure at the time of admission, and 32.5% of patients had elevated liver enzymes, consistent with the research results of some authors around the world [11]. The most common cause of kidney failure is tumor lysis syndrome, where cancer cells die on their own in large numbers, or under the influence of chemotherapy. 89.9% of patients showed increased LDH and 20.3% of patients had increased uric acid; 27.1% of patients had elevated CRP. According to Shimony, CRP is a sensitive biomarker to find febrile neutropenia and blood stream infections [12]. Considering the cerebrospinal fluid at the time of admission, 100% of patients had CNS1, much higher than the study of other authors. According to Al-Sudairy, 83% of patients had CNS1, 11.8% of patients had CNS2 and 5.2% of patients had CNS3 [5], or according to Fadoo, 93.4% of patients had CNS1, 5.8% had CNS 2 and 0.8% of patients had CNS3 [4].
The percentage of abnormal chromosomes was low, 9.4% of patients had hyper diploid chromosomes, and 3.1% of patients had extra chromosomes. Compared with other studies, according to Fadoo, up to 10.7% of patients had chromosomal hyperdiploidy, 5.1% of patients had hypodiploid and 84.2% of patients had a normal chromosome set [4]. According to Al-Sudairy, 24.6% of patients had hyperdiploid chromosomes. The reason for low results may be a small sample, not being able to reflect properly. In ALL, patients with hyperdiploid have a better prognosis [5].
The results of the analysis with multiplex PCR showed that 12.1% of patients had TEL/AML1, 4.8% of patients had BCR/ABL1 fusion, 3.6% of patients had E2A/PBX1 fusion, 2.4% of patients had MLL/AF4 fusion and 1.2% of patients had SET/NUP214 fusion. Our results had some similar figures, and some were much lower than those of other authors. According to Fadoo, the expression percentage of fusion genes BCR/ABL1, TEL/AML1, and MLL/AF4 were 7.3%, 13.2%, and 4.6%, respectively [4]. According to Al-Sudairy, the rate of BCR/ABL1 fusion was 4.2% and the rate of E2A/PBX1 and MLL/AF4 fusions were 3.6% and 2.5%, respectively [5]. With the multiplex-PCR, our result found new fusion comparing with other previous results in Vietnam. It was SET/NUP214 fusion. This fusion gene often occurs in T-ALL and is still poorly understood [13]. The cause of the difference in the ratio can be explained by the small sample, not being able to represent. According to Inaba, the fusion gene TEL/AML1 has an excellent prognosis, and fusion gene E2A/PBX1 has a favorable prognosis. In contrast, the fusion gene BCR/ABL1 has a poor prognosis and need to add tyrosine kinase inhibitors in treatment [14]. Similar, the fusion gene MLL/AF4 also has a dismal prognosis [14].
Conclusion
The most common symptoms in acute lymphoblastic leukemia are anemia, fever, hepatomegaly, splenomegaly, peripheral lymphadenopathy, hemorrhage, and bone pain.
Gene mutations detection plays a crucial role in the prognosis and modification of treatment for patients.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Funding: None
Conflict of interest
The author(s) declared no conflicts of interest.
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Comparison of different scoring systems for predicting mortality and morbidity after neonatal heart surgery
Dilek Yavuzcan Öztürk 1, Hatice Dilek Ozcanoglu 2
1 Department of Neonatology, 2 Department of Anaesthesiology and Reanimation, Istanbul Saglik Bilimleri University, Basaksehir Cam and Sakura Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21376 Received: 2022-08-31 Accepted: 2022-10-05 Published Online: 2022-10-10 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S101-105
Corresponding Author: Dilek Yavuzcan Öztürk, Department of Neonatology, Istanbul Saglik Bilimleri University, Basaksehir Cam and Sakura Hospital, Başakşehir Mahallesi, G-434 Street, No: 2L, Başakşehir, Istanbul, Turkey. E-mail: drdileky@gmail.com P: +90 212 909 60 00 / +90 505 769 48 44 F: +90 212 909 60 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5270-4294
Aim: In this study, it was aimed to evaluate the effect of neonatal intensive care scoring systems and surgical-related scoring systems, which were used after congenital heart surgery, on predicting mortality and morbidity in newborns.
Material and Methods: This study was carried out on patients who underwent neonatal cardiac surgery and were followed in the pediatric cardiac intensive care unit between July 1, 2021 and July 1, 2022. Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality categories (STS-EACTS MC) STAT score, Vasoactive inotrope score (VIS) and Vasoactive Ventilation Renal (VVR) scores in the first 48 hours of newborns who were admitted to the intensive care unit after the cardiac surgery were calculated. The effects of these results on hospital morbidity (long stay in intensive care unit=longer than the upper 25th percentile of total stay) and hospital mortality (developing before the first 30 days after surgery) were investigated. The results were evaluated statistically.
Results: One hundred and sixty cases (50% male) were included in the study. The median age was 7 days (IQR 3 -10 days); 30 percent had single ventricular physiology. The duration of intensive care stay was >216 hours and the total mortality was 12.5% (n=20). A STAT ≥ 4 score was a strong predictor of both long intensive care stay (OR 2.1) (CI 95% 1.3-3.4 P=0.04) and hospital mortality (OR 4.2) (CI 95% 2.2-9) P = 0.008).
The maximum 48th-hour VVR score was a strong predictor of both long intensive care stay (OR 1.8;(CI 95% 1.3-2.2 P=0.001)) and hospital mortality (OR 1.56;(CI 95% 1.3-2.9)).
Discussion: STAT and VVR scores can help to predict mortality and morbidity in newborns after cardiac surgery.
Keywords: Newborn, Congenital Heart Surgery, Scoring Systems
Introduction
Congenital heart diseases (CHD) are the most common cause of acute heart failure in newborns and may result in low cardiac output after birth. Due to the wide spectrum of CHD, patients might have different pathophysiological clinical conditions. Depending on the type of CHD, some patients can be discharged home, but some may require follow-up in the intensive care unit. Approximately 25% of the cases underwent either interventional treatment (angiography or surgical) within the first year of life [1].
Various scoring systems are used to evaluate the morbidity and mortality results after congenital heart surgery [2-3]. In general, the basic features required in these scoring systems are as follows: easy data entry, creation of a common and reliable database, reduction in the cost of intensive care units, efficient use of resources, the guidance of clinical decisions and applications and provision of objective evaluation. However, the issue of which scoring system is the best is still controversial.
Although RACHS-1 (Risk Adjustment in Congenital Heart Surgery), Aristotle Basic Complexity Score (ABC), Aristotle Comprehensive Complexity Score (ACC) and Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality categories (STS-EACTS MC) STAT scores are frequently used as a scoring system, they are mostly based on the difficulty of surgical operation, and they don’t contain enough data about the clinical outcome of the intensive care follow-up [4-5]. In some studies, it has been suggested that the STAT score is the most successful scoring system for predicting mortality and morbidity among these four systems [5-6].
Lactate and vasoactive-inotropic score (VIS) were frequently used to evaluate the clinical status and outcome in pediatric cardiac intensive care, but they can modestly predict the outcome [7]. Recently, for the postoperative period, it is suggested that the vasoactive-ventilation-renal (VVR) score can be used as a strong marker [8].
There are limited studies on the use of these different scoring systems during newborn period. In this study, we investigated the efficiency of STAT score and VVR scores, for predicting hospital mortality and morbidity, in different types of newborn CHD patients.
Material and Methods
This study was conducted, between 1 July 2021 and 1 July 2022, on patients who underwent neonatal heart surgery operation and were followed up in the pediatric cardiac intensive care unit. Patients requiring ECMO support, premature newborns, permanent pacemaker implantation patients and patients transferred to a different unit within the first 72 hours after the surgery were excluded from the study. This retrospective study was approved by the institutional ethics committee and was conducted in accordance with the principles of the Declaration of Helsinki.
The preoperative demographic data (gender, weight, and additional genetic syndromes), anatomical diagnosis, surgical data, clinical follow-up, and postoperative intensive care unit reports of the study group were evaluated.
Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality categories (STAT) were applied according to the analysis reported in the literature. The mortality risk was estimated for 148 procedure types, using real data from 77,294 patients (33,360 patients from the EACTS and 43,934 patients from the STS) between 2002 and 2007. Using Bayesian statistics that fit the data for small denominators, mortality rates were calculated for each procedure. For the STAT, the scale ranged from 0.1 to 5.0, and a corresponding mortality category level between 1 and 5 was assigned (level 1, 0.1-0.3; level 2, 0.4-0.7; level 3, 0.8-1.2; level 4, 1.3-2.6; level 5, 2.9-5.0) [9].
Urea and creatinine values were retrospectively collected from the hospital database from biochemical blood values, which are routinely gathered preoperatively, at postoperatively 24 hours and 48 hours. Acute kidney injury (AKI) was classified using the AKI network staging system.
Postoperative data of arterial blood gas parameters including PH, partial pressure of carbon dioxide (PaCO2), and partial pressure of oxygen (PaO2) at admission in PICU, 24 h, and 48 h postoperatively along with the corresponding ventilator settings, including peak inspiratory pressure (PIP), positive end-expiratory pressure (PEEP), mean airway pressure, and respiratory rate (RR) in the volume-controlled mode of ventilation were collected.
Doses of inotropic and vasopressor agents were also recorded at the time of each blood gas analysis. Postoperative serum creatinine was recorded at admission, 24 h, and 48 h postoperatively.
VIS and VVR scores were calculated for all patients at the study time point. VIS was calculated using formulae; VIS = Dopamine dose (μg/kg/min) + Dobutamine dose (μg/kg/min) +100 × Epinephrine dose (μg/kg/min) +10 × Milrinone dose (μg/kg/min) +10000 × Vasopressin dose (μg/kg/min) +100 × Norepinephrine dose (μg/kg/min) [7]. Ventilation index (VI) was calculated using the formula: VI = RR × (PIP−PEEP) × PaCO2/1000; Δ Cr was calculated by subtracting serum creatinine (in mg/dl) at the time of each measurement with preoperative serum creatinine and VVR using the formula: VVR = VIS + VI + (Δ Cr × 10) [8]. For patients whose postoperative serum creatinine values were less than preoperative values, Δ Cr was taken as 0. For patients not requiring ventilator support at the time of measurement, VI was taken as 0.
In this study, our two primary outcomes were operative mortality and Pediatric Cardiac Intensive Care Unit Length of Stay (PCILOS). Operative mortality included all the deaths that occurred during the hospital stay when the operation was performed, and the deaths occurred after discharge within 30 days of the procedure. For further analysis of PCILOS, data were dichotomized as the upper (worst) 25th percentile versus lower (best) 75th percentile. PCILOS in the upper 25th percentile was considered a prolonged Pediatric cardiac intensive care unit length of stay.
In each scoring system, a higher score indicates a higher risk of mortality. For patients undergoing multiple procedures, the procedure with the highest level was scored. The scores of each patient were calculated according to the STAT, VIS and VVR scoring systems and recorded.
Statistical analysis
Data were analyzed using SPSS (Statistical Package for Social Sciences) statistical software, version 15 for Windows. Median with range was used to describe continuous data whereas absolute count with percentage was used for categorical data. Data were analyzed for correlation between the scores and outcome using Spearman’s rho.
Univariate analysis was performed for demographic and clinical characteristics of patients to predict our two primary outcomes using the Mann–Whitney U-test, Chi-square test, or Fisher’s exact test as appropriate for individual variables. Significance variables were included in the multivariate logistic regression model, and the odds ratio (OR) was calculated. P < 0.05 was considered significant. Analysis of the discriminatory ability of the risk stratification methods was per¬formed using the C statistic comparison with the ROC curves of the two methods.
Results
There were 160 cases (50% male) during the study period. The median age was 7 days (IQR 3-10 days) and the median weight was 3 kg (IQR 2,8 – 3,2 kg). The most common diagnoses of the cases were aortic arc hypoplasia (n=40), transposition of the great arteries (n=35), Hypoplastic left heart syndrome (n=25), and total abnormal pulmonary venous return anomaly (n=20). Single ventricle physiology was seen the 30% of the cases, and 130 of them (80%) were STAT≥4. The main characteristics of the cases are shown in Table 1.
The median ICU stay was 7 days (IQR 5- 9 days). Prolonged intensive care stay (PICS) was observed in 45 cases and mortality in 20 cases. The length of PICS was > 216 hours and total mortality was 12,5% (n=20).
The median VIS was 10 (IQR 8-12) and the median VVR score was 40 (IQR 35-45) at hour 0. The median VIS was 7 (IQR 5-10) and the median VVR score was 30 (IQR 25-35) at the 24th hour. The median VIS was 5 (IQR 3-7) and the median VVR score was 16 (IQR 14-18) at the 48th hour. The VVR score was higher at each measurement point compared to the corresponding VIS. According to correlation analysis, VVR score predicted endpoints better than VIS at each measurement point. In particular, VVR 0.hour PICS c index= 0.76( CI:0.72-0.80), mortality c index= 0.80(CI: 0.76-0.85). VVR 24th hour PICS c index= 0.78(CI:0.74-0.82), mortality c index= 0.83( CI: 0.80-0.86). VVR 48th hour PICS c index= 0.87( CI:0.82-0.92), mortality c index= 0.82(CI: 0.80-0.84). Maximum 48th hour VVR score PICS c index = 0.88 (CI: 0.86-0.90), mortality c index = 0.92 (CI: 0.90-0.93). The maximum 48th-hour VVR score was the most powerful of all to show mortality (0.92) and morbidity (0.88) (Table 2).
The evaluation results of the factors affecting the prolonged intensive care unit stay are shown in Table 3. When multivariate regression analysis of factors with p< 0.05 was performed, the following factors were found to independently increase the risk; STAT score ≥ 4 OR 2.1(CI %95 1.3-3.4 P=0.04), AKI> 2 OR 1.1(CI %95 1-2.2 ) P = 0.04), presence of postoperative arrhythmia OR 4.5(CI %95 2.4-6.6 P=0.001), the maximum VVR score OR 1.8;(CI % 95 1.3-2.2 P=0.001) and VVR score OR 1.44;(CI1.2-1.6 P=0.001).
The evaluation results of the factors affecting mortality are shown in Table 3. When multivariate regression analysis of factors with p< 0.05 was performed, STAT score ≥ 4 OR 4.2 (CI %95 2.2-9) P = 0.008) AKI> 2 OR 3.1(CI %95 1-9) P = 0.02), the maximum VVR score OR 1.56;(CI % 95 1.3-2.9), P=0.001) and the 48th-hour VVR score OR 1.30 (CI %95 1.2-1.5), P = 0.001) were found to be independent risk factors.
VVR score at 48 hours was further dichotomized in high and low to simplify its interpretation. When the PICS duration cut-off was taken as 25, the sensitivity and specificity of the maximum 48th-hour VVR score were 80% and 75%, respectively. And when the hospital mortality cut-off was taken as 40, the sensitivity and the specificity of the maximum 48th-hour VVR score were 93% and 86%, respectively.
Discussion
In this study, the power of different scoring systems to predict morbidity and mortality in newborns undergoing congenital heart surgery was investigated. We found that high STAT and VVR scores strongly predict mortality and morbidity and with these aspects this study is one of the limited studies in the literature.
The scoring systems are needed for the comparison and analysis of mortality and morbidity of congenital heart diseases due to the large number and complexity of the surgical operations. RACHS-1, ABC, ACC and STAT mortality scores are used for classification according to these surgical features. Risk Adjustment in Congenital Heart Surgery has been the first system used for this purpose. It is rather an easier model, because it needs less data. Although it does not contain all cardiac procedures and is based on personal foresight, it is widely used to determine mortality. The European Association for Cardiothoracic Surgery defined the Aristotle scoring system as two separate scoring systems, namely, ABC and ACC, in 2014. The first score was the Basic score, which adjusted only for the complexity of the procedure. The second score was the Comprehensive score, which took into account specific procedure-dependent and procedure independent patient characteristics. It is divided into four levels according to difficulty. Society of Thoracic Surgeons and the European Association for Cardiothoracic Surgery mortality categories (STAT) is the most recent scoring system estimating mortality based on processing data from a database containing 148 different procedures. It is divided into five subgroups according to difficulty level [4,6]. STAT is the most recent of these scores and its effectiveness has been demonstrated in different studies.In the series of Yıldız et al [6] with 1950 cases and O’Brien [9], it was stated that the best surgical scoring system was STAT. We evaluated the STAT system in our study. In our newborn series, STAT score ≥ 4 predicted mortality and morbidity as an independent risk factor.
Recently, it has been stated that the scoring systems used after the operation will not be sufficient alone, and the evaluation of all body systems along with it would be useful. Miletic et al. [8] were the first who introduced the VVR scoring system, which enables the evaluation of heart, lung and kidney functions together. In their study of 222 cases younger than 365 days who underwent surgery for congenital heart disease and without residual mixing lesion or single ventricle physiology, they suggested that the VVR score is a powerful method for evaluating cardiac surgery outcomes.
The most important advantage of the VVR score compared to other indices is that it includes patients who are hemodynamically stable and do not need much support, but who have postoperative lung and kidney damage. Making these calculations with routine laboratory data in clinical practice and a simple calculation at the bedside makes it easier to use. However, the main problems for widespread clinical use in a heterogeneous disease group such as congenital heart diseases are the uncertainties about which age group, at what time postoperatively, and what the cutoff values should be. With more studies to be done in the future, the patient’s age group and disease-specific cut-off values will be determined [8,10,11].
Öztürk et al. [10] suggested that the 48th hour VVR score could predict mortality and morbidity as an independent risk factor in their series of 340 cases. Zubarioğlu et al. [11] in their study of neonatal cardiac surgery cases stated that the VVR score in the maximum first 72 hours was a strong marker in determining intensive care and hospital mortality.
In our study, a maximum 48th-hour VVR cut-off value of >25 was found associated with prolonged intensive care unit time and a cut-off value of >40 VVR was found associated with mortality.
Alam et al. [12] compared the power of VVR and VIS values in predicting clinical outcomes in their study and found that VVR had a significantly better prediction at all times. In their study of 164 cases, Sherer reported that VVR predicted prolonged ICU duration better than lactate and VIS values in the early postoperative period [3]. Findings were similar in the study by Öztürk et al [10]. In our study, the relationship between VVR and VIS was in parallel with the studies above. This shows the direct contribution of respiratory and renal parameters to postoperative outcomes in newborn cases.
In our study, other factors affecting mortality and morbidity were also evaluated independently from the VVR score. Arrhythmia and AKI > 2 were found to be other effective factors of morbidity and mortality. These results were similar to previously reported studies [12-14].
Limitation
The main limitation of the study is its retrospective nature with a limited number of cases from a single center. The heterogeneity of the cases is another limitation.
Conclusion
We validated the utility of the STAT and VVR scores in neonatal cardiac surgery for critical congenital heart disease. STAT and VVR scores can help predict mortality and morbidity in newborns after cardiac surgery. There is a need for studies with a larger number of patients on this subject.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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2. Kogon B, Oster M. Assessing surgical risk for adults with congenital heart disease: are pediatric scoring systems appropriate. J Thorac Cardiovasc Surg. 2014;147(2):666–71.
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4. Jacobs JP, Jacobs ML, Lacour-Gayet FG, Jenkins KJ, Gauvreau K, Bacha E, et al. Stratification of complexity improves the utility and accuracy of outcomes analysis in a Multi-Institutional Congenital Heart Surgery Database: Application of the Risk Adjustment in Congenital Heart Surgery (RACHS-1) and Aristotle Systems in the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database. Pediatr Cardiol. 2009;30(8):1117-30.
5. Cavalcanti PE, Sá MP, Santos CA, Esmeraldo IM, Chaves ML, Lins RF, et al. Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons. European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score. Braz J Cardiovasc Surg. 2015;30(3):148-58.
6. Yıldız O, Kasar T, Öztürk E, Tüzün B, Altın HF, Onan İS, et al. Analysis of congenital heart surgery results: A comparison of four risk scoring systems. Turk Gogus Kalp Damar Cerrahisi Derg. 2018;26(2):200-6.
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Dilek Yavuzcan Öztürk, Hatice Dilek Ozcanoglu. Comparison of different scoring systems for predicting mortality and morbidity after neonatal heart surgery. Ann Clin Anal Med 2022;13(Suppl. 2):S101-105
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Crystallized phenol treatment is a good alternative for the pilonidal disease in teenagers
Ramazan Saygın Kerimoğlu
Department of Gastrointestinal Surgery, Konya City Hospital, Konya, Turkey
DOI: 10.4328/ACAM.21378 Received: 2022-09-04 Accepted: 2022-10-05 Published Online: 2022-10-11 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S106-110
Corresponding Author: Ramazan Saygın Kerimoğlu, Department of Gastrointestinal Surgery, Konya City Hospital, Akabe Street, Karatay, Konya, Turkey. E-mail: saygin_k@yahoo.com P: +90 505 319 08 34 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3149-9636
Aim: Although many surgical procedures have been tried, the best treatment option remains controversial in teenagers. The purpose of this study was to assess the long- term outcomes of crystallized phenol therapy in the treatment of pilonidal sinus disease in teenage patients.
Material and Methods: A retrospective review from 1996 to 2019 of teenagers with pilonidal disease undergoing crystallized phenol treatment for primary pilonidal disease was performed. Data collection included demographics, features of sinus, total procedures performed, healing time, recurrence, follow-up time and the last status of patients over a twenty- year period.
Results: A total of 235 teenagers with pilonidal disease (162 boys, 73 girls) with a mean age of 16.32 (range 12–18) years who were reached during the study period were evaluated. The overall success rate was 73.61% in long- term period. It was determined that the recurrence rate was higher in patients with multiple sinus orifices at admission, more CPT sessions, and a longer recovery period (p=0.01, p=0.03, and p=0.02, respectively). It was observed that the predisposing factors accused in the etiology of pilonidal disease had no effect on recurrence after treatment (p>0.05).
Discussion: Crystallized phenol treatment has also been successful in long-term folow-up in teenage patients. It can be safely used as the first option in the treatment of pilonidal disease in the teenage population too.
Keywords: Pilonidal Disease, Crystallized Phenol, Teenage, Risk Factors, Nonoperative Treatment
Introduction
Pilonidal disease (PD) is a benign, chronic, inflammatory disease of the skin located especially in the sacrococcygeal region. Although it is common in adult males, it is also seen in teenagers [1-6]. In adults, being overweight, excess hair in the intergluteal cleft, prolonged sitting times, family history and poor hygiene are acknowledged as predisposing factors [7,8]. Although the idea of an acquired theory in PD etiology is accepted today, it is unclear whether congenital theory or acquired factors have an effect on the increase of PD in teenagers.
PD treatment remains a mystery in teenagers, as does its etiology. Due to the limited number of studies on the treatment of PD in teenagers, they are generally treated according to the principles of adult treatment. Currently, wide local excision with or without flap technique is recommended most [9-,12]. Therefore, some authors argue that surgery is necessary at an early age due to the fact that long-term risk rates in teenagers are higher [13]. But, these therapies can result in significant morbidity, long healing times, and a high risk for recurrence. More recently, minimally invasive techniques, including fibrin glue obliteration [9,14], minimal excision [15], and crystallized phenol [4] have been described in teenagers. These treatments reportedly offer quicker healing and return to normal activities with acceptable recurrence rates. However, long-term follow-up data are not available. We have used crystallized phenol application in adults for a long time as a nonoperative treatment method that can be easily applied with minimal complications and had very successful results in both primary and recurrent PD treatment [16,17]. We have applied this method, which is successful in both adults and teenagers. We could not find large series with long-term follow-up of the treatment of PD with crystallized phenol treatment (CPT) in teenagers in the literature.
In this study, we aimed to present the long-term results of our crystallized phenol application, the efficiency of CPT and predisposing factors in a wide case series in teenagers aged 12-18 years with PD.
Material and Methods
Patient Selection
The records of 415 PD patients aged 12-18 years who underwent CPT between March 1996 and February 2019 were evaluated. These prospectively collected data were analyzed retrospectively. Patients who were followed for less than one year (N= 135) were excluded from the study considering that true recurrences cannot fully develop within such a short period of time. Furthermore, 45 out of 415 patients previously operated using any technique but had postoperative recurrent PD (N=41) and those who could not complete or discontinued their treatment for any reason (N=4) were excluded from the study. For this reason, 235 patients were included in the study (Figure 1: flowchart).
Study Design
This study was performed in accordance with the declaration of the Helsinki Protocol. This study was approved by the institutional review board at KTO Karatay University, Medical School, Konya, Turkey (IRB no. 2021/007). An informed consent form was obtained from the legal guardians of all patients. The teenage patients diagnosed with PD were evaluated with regard to family history of PD, body mass index (BMI, kg/m2), skin tone, pilosity levels, smoking history, and time spent sitting per day.
The presence of PD was investigated in the first and second-degree relatives of the patients to identify any family history. The patients were categorized into two groups according to the presence or absence of a family history of PD. Skin tone evaluations of all patients were performed visually based on the Fitzpatrick scale [18]. The parents of the patients were asked to record the time spent sitting per day. Accordingly, the patients were categorized into two groups: sitting for less than 6 hours or more than 6 hours a day.
The presence of purulent discharge from the sinus orifice and the presence of signs of inflammation or abscess formation in this area were evaluated as acute PD. The presence of serous discharge from the sinus orifice and the absance of signs of inflammation and abscess formation were evaluated as chronic PD. It was investigated whether the factors mentioned above affect the number of CPT applications, healing time and recurrence.
Crystallized Phenol Application
Crystallized phenol treatment was performed as described by Dogru et al. [17], who first described and applied it. The day before the procedure, patients were asked to clean hairs from the waist to the middle of the thigh with depilatory creams or epilation. The patients were admitted in a prone position. After local anesthesia around the sinus holes, the sinus was entered with a thin mosquito clamp and the hairs in the sinus were removed. The skin was covered with nitrofurantoin pomade (Furacin, Eczacıbaşı İlaç San ve Tic. A.S., İstanbul, Turkey) in order to prevent skin irritation. Crystallized phenol with the same clamp was filled into the sinus hole until the sinus cavity was filled. All procedures were outpatient. No patients were given antibiotics and analgesic treatment.
Follow-up
Patients were called for control with an interval of 3-week. The closing of the sinus hole and the complete disappearance of the discharge were considered healing. After the treatment of the patients was finished, their annual follow-up was performed. All patients were offered hair removal of the sacrococcygeal area once a month for 6 years. Reopening the previously closed sinus openings at least 6 months later was considered a recurrence. If the sinus openings were reopened in less than 6 months, the treatment failure was accepted, and CPT application was continued. All patients were contacted by e-mail or phone and asked whether they had, recurrence, treatment at another institution or the last status of their disease in February 2019. Patients who could not be reached in either way were evaluated according to their records at the last admission.
Statistical Analysis
Mean, standard deviation, median, lowest, highest, frequency and ratio values were used in the descriptive statistics of the data. The distribution of variables was measured by the Kolmogorov-Smirnov test. The Mann-Whitney U and the Kruskal-Wallis tests were used to analyze quantitative independent data. The Chi-square test was used in the analysis of qualitative independent data. A multiple logistic regression model was implemented to determine the independent variables associated with PD. SPSS 22.0 packed program was used in the analysis.
Results
In this study, we presented data of 235 patients whose records were completely accessible. The mean age of the patients was 16.32 (range, 12-18) and the majority were males (68.9%). All patients were discharged on the same day. Five (2.85%) patients were treated with topical therapy because of irritation at the wound site. No major complications were observed in any patient.
The mean follow-up time was 37.36 (range, 12-235) months. The majority of patients had chronic sinus presentation (90.2%) and a mean number of CPT sessions was 2.1 (range, 1-10). Although one session of CPT was sufficient in half of the patients, only 8.9% needed 5 or more CPT sessions.
One hundred thirty-one (55.7%) patients continued their lives without any problems after CPT. In addition, there were 22 (9.36%) patients who could not be reached but no recurrence was observed during their follow-up period. The mean follow-up period of these patients who could not be reached was 31.50 ± 22.19 (13-93) months.
The disease recurred in 82 (34.8%) patients, 20 (24.39%) of whom were applied re-CPT and now have no problems, 18 (21.95%) preferred surgery after recurrence. Thirty three (40,2%) patients with recurrence did not accept retreatment and 11 (13,4%) patients were excluded from follow-up voluntarily (Figure 1). Thus, the number of patients who we were administered successfully was 173 (131+22+20). Our success rate was 73.61%.
Crystallized phenol treatment was re-applied to patients who relapsed after CPT and accepted re-treatment. After the first recurrence, 13 patients refused re-CPT and preferred to undergo surgery, in 20 patients re-CPT application was continued. Among 20 patients, 6 patients experienced a second recurrence and 1 patient experienced a third recurrence and they were treated with re-CPT succesfully. Despite the recurrence, we achieved success in all patients, we continued CPT. The mean number of recurrences was 1.22 (1-3). Every recurrence required fewer CPT sessions. We observed that 92.6% of recurrences were in the first 5 years; 7.3% of them were between 5-10- year period. No recurrence was observed in 27 patients who were followed up 10 years later.
The predisposing factors in PD etiology and demographic data of patients are seen to affect recurrence after CPT (Table 1). Recurrence was higher in male patients (OR: 0,501, 95%CI 0,27-0,93, p=0.01). It was observed that the predisposing factors accused in PD etiology had no effect on recurrence after CPT (p>0.05). We performed a multivariable logistic regression analysis (with the predisposing factors being recurrence), and the possible predictive variables were age and sex. None of these variables excluding sex were predictive of recurrence (95% CI 0.05–1,89, p = 0.06).
Table 2 shows relationship between sinus features, CPT application and follow-up time with recurrence. It was determined that the recurrence rate was higher in patients when number of primary opening before CPT, the number of CPT applications and healing time were high. (respectively, p=0.01, p=0.03, p= 0,02).
Discussion
Although PD is common in adults, it is not uncommon in teenagers [19,20]. However, there are very few studies on PD and its treatment in teenagers [1-6]. All these studies have low quality and risk of bias due to the small number of participants and the short follow-up period [9]. In one of these studies that reported a 2-year follow-up of off-midline flap methods, the recurrence rate was 8% in teenagers [9]. However, the recurrence rate was reported to be between 1-6.7% in long-term follow-up in adults. [18]. Although it is known that the recurrence rates of sinus excision and open healing methods were lower compared to flap methods in adults, it has been reported that the recurrence rates of open healing methods were higher than flap methods in teenagers [21]. These results thought that PD has a different progression in teenagers than in adults. Therefore, we planned this study to evaluate the long-term results of the CPT method, which has successful results in adults, in teenagers. This study has the longest follow-up period and the largest number of case series on PD treatment in teenagers to date.
Doğru et al, who first applied CPT in the treatment of PD in adults, reported a success of 84.3% in 20 years of follow-up [17]. Ates et al. who first mentioned the results of CPT in the treatment of PD in teenagers to date, reported that recurrence rate in 40 patients who underwent CPT during a mean follow-up of 8 months was 2.5% [4]. Moreover Gulpinar et al. reported a case report with a short follow-up that crystallized phenol application in adolescence pilonidal disease seems to be a promising non-operative therapy [22]. However, longer follow-up periods are needed to determine the right recurrence rates in PD. For this reason, our study is the first study that evaluated the result of CPT in teenagers with the highest number of patients and the longest follow-up period.
In this study, our 20-year success rate was determined as 76.5%. This success rate belongs to the group of patients who never quit our treatment and are compatible with us. Patients who did not come to treatment after recurrence of PD or refused our treatment and preferred surgery were evaluated as the groups in which we failed. Although our first recurrence rate after CPT was 33.1%, we achieved success in all of the patients we applied CPT again after recurrence. If the patients in the unsuccessful group (patients who did not continue treatment or preferred surgery) continued their treatment, our success rate would be probably higher. We did not recommend surgery to any of our patients with recurrence after CPT because CPT can be easily applied again in recurrences after CPT, and the number of applications decreases more after each recurrence as seen in our study. For this reason, we believe that it would be appropriate to consider the treatment of recurrent cases with CPT after CPT. It has been reported in the literature that the recurrence rate after PD surgery in teenagers was between 13-28% [1,4,6]. Our total recurrence rate is 22.8 and it is similar to the surgical results in the literature. In addition, we have no major complication as it is seen in surgeries.
Our success rate of single session CPT in the treatment of PD was 49.7%. Recurrence was observed in 25% of these patients during their follow-up. The success of a single session of phenol administration has been reported between 64-70% in adults [23]. But a pseudo-membrane sometimes forms in the sinus orifice after one session of CPT, which may mislead the clinician according to our experience. Therefore, we applied re-CPT by reopening the sinuses orifice where we saw pseudo-membranes. In our study, we think that single-session CPT is not an appropriate method, since it has achieved more than 90% success in 4 or more applications. It has been reported that the incidence of PD in teenagers is similar between men and women, unlike adults [3,5]. However, in our study, the male to female ratio was 2,2:1. We think that this is because it is difficult for women to apply to the doctor with this complaint due to local cultural characteristics in our region. In addition, more recurrences were observed after CPT in male patients.
Despite these high success rates of CPT applications, some clinicians are hesitant about the use of crystallized phenol, especially in the pediatric population, for concerns of toxic effects such as muscle weakness, convulsions and coma. However, we did not encounter any of the toxic effects in any of our patients in this series. Therefore, we think that CPT can be also applied safely in the pediatric population. In addition, there is no evidence in the literature regarding the toxic effects of CPT used in the treatment of PD in the pediatric population.
The study had some limitations. Since it has a 20-year follow-up period, 13.1% of the patients were out of follow-up and the patients could not be reached. In addition, the CPT that we apply to all patients without using a classification for PD shows a heterogeneous distribution because it contains the results.
Conclusion
CPT application, which is successfully applied in the treatment of PD in adults, has been observed to be successful in the long term in teenagers. Since CPT is inexpensive, can be applied as outpatient, is a non-invasive procedure, has comparable results to surgical procedures, and does not cause loss of work for patients, it can be safely applied as the first option in the treatment of PD in teenagers. Even in relapses after CPT, repeated CPT application should be considered before making a surgical decision.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. Arda IS. Pilonidal sinus disease in children. J Pediatr Surg. 2008;43(10):1950; author reply 1950-1.
3. Yildiz T, Elmas B, Yucak A, Turgut HT, Ilce Z. Risk Factors for Pilonidal Sinus Disease in Teenagers. Indian J Pediatr. 2017;84(2):134-8.
4. Ates U, Ergun E, Gollu G, Sozduyar S, Kologlu M, Cakmak M, et al. Pilonidal sinus disease surgery in children: the first study to compare crystallized phenol application to primary excision and closure. J Pediatr Surg. 2018;53(3):452-5.
5. Nasr A, Ein SH. A pediatric surgeon’s 35-year experience with pilonidal disease in a Canadian children’s hospital. Can J Surg. 2011;54(1):39-42.
6. Fike FB, Mortellaro VE, Juang D, Ostlie DJ, St Peter SD. Experience with pilonidal disease in children. J Surg Res. 2011;170(1):165-8.
7. Bolandparvaz S, Moghadam Dizaj P, Salahi R, Paydar S, Bananzadeh M, Abbasi HR, et al. Evaluation of the risk factors of pilonidal sinus: a single center experience. Turk J Gastroenterol. 2012;23(5):535-7.
8. Harlak A, Mentes O, Kilic S, Coskun K, Duman K, Yilmaz F. Sacrococcygeal pilonidal disease: analysis of previously proposed risk factors. Clinics (Sao Paulo). 2010; 65:125–31.
9. Hardy EJO, Herrod PJ, Doleman B, Phillips HG, Ranat R, Lund JN. Surgical interventions for the treatment of sacrococcygeal pilonidal sinus disease in children: A systematic review and meta-analysis. J Pediatr Surg. 2019;54(11):2222-33.
10. Milone M, Velotti N, Manigrasso M, Anoldo P, Milone F, De Palma GD. Long-term follow-up for pilonidal sinus surgery: A review of literature with metanalysis. Surgeon. 2018;16(5):315-20.
11. Braungart S, Powis M, Sutcliffe JR, Sugarman ID. Improving outcomes in pilonidal sinus disease. J Pediatr Surg. 2016;51(2):282-4.
12. Nasr A, Ein SH. A pediatric surgeon’s 35-year experience with pilonidal disease in a Canadian children’s hospital. Can J Surg. 2011;54(1):39-42.
13. Doll D, Matevossian E, Wietelmann K, Evers T, Kriner M, Petersen S. Family history of pilonidal sinus predisposes to earlier onset of disease and a 50% long-term recurrence rate. Dis Colon Rectum. 2009;52(9):1610-5.
14. Smith CM, Jones A, Dass D, Murthi G, Lindley R. Early experience of the use of fibrin sealant in the management of children with pilonidal sinus disease. J Pediatr Surg. 2015;50(2):320-2.
15. Speter C, Zmora O, Nadler R, Shinhar D, Bilik R. Minimal incision as a promising technique for resection of pilonidal sinus in children. J Pediatr Surg. 2017;52(9):1484-7.
16. Aygen E, Arslan K, Dogru O, Basbug M, Camci C. Crystallized phenol in nonoperative treatment of previously operated, recurrent pilonidal disease. Dis Colon Rectum. 2010;53(6):932-5.
17. Dogru O, Kargin S, Turan E, Kerimoğlu RS, Nazik EE, Ates D. Long-term outcomes of crystallized phenol application for the treatment of pilonidal sinus disease. J Dermatolog Treat. 2022;33(3):1383-90.
18. Ravnbak MH. Objective determination of Fitzpatrick skin type. Dan Med Bull. 2010;57(8):B4153.
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20. Nasr A, Ein SH. A pediatric surgeon’s 35-year experience with pilonidal disease in a Canadian children’s hospital. Can J Surg. 2011;54(1):39-42.
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Ramazan Saygın Kerimoğlu. Crystallized phenol treatment is a good alternative for the pilonidal disease in teenagers. Ann Clin Anal Med 2022;13(Suppl. 2):S106-110
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Investigations of factors affecting mortality in our ECMO (Extracorporeal membrane oxygenation) applications
Gönül Erkan 1, Ahmet Eroğlu 2
1 Department of Anesthesiology and Reanimation, Health Sciences University, Ahi Evren Training and Research Hospital, 2 Department of Anesthesiology and Reanimation, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
DOI: 10.4328/ACAM.21384 Received: 2022-09-06 Accepted: 2022-10-08 Published Online: 2022-10-19 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S111-115
Corresponding Author: Gönül Erkan, Department of Anesthesiology and Reanimation, Health Sciences University, Ahi Evren Training and Research Hospital, Trabzon, Turkey. E-mail: gonul_erkan@hotmail.com P: +90 505 375 40 93 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2028-4288
Aim: Extracorporeal membrane oxygenation (ECMO) is a life support application used for life-threatening pulmonary or cardiac injuries that could not be treated with traditional treatment strategies successfully. In our study, we investigated factors affecting mortality in patients using ECMO in our clinic.
Material and Methods: In the study, 74 patients over the age of 18 who used ECMO were retrospectively examined. Patients were divided into two groups as those who survived after ECMO support (Group 1) and those who ended up with mortality (Group 2). Demographic data and comorbidities of patients, APACHE-2 score, RESP score, indications, applied ECMO type, inotropic treatments, blood products used and their quantities, non-ECMO support applications, and complications were studied.
Results: Of the 74 ECMO patients, 43 (58.11%) were male and 31 (41.89%) were female. The number of patients who ended up with mortality was 42(56.76%) and the number of those who survived was 32 (43.24%). Age, APACHE 2 and RESP scores, and ECMO flow were found to be statistically significantly higher in the group with mortality than the in the survival group (p<0.05). In addition, the rate of thrombocytopenia and the quantity of thrombocyte suspension used were higher in the mortality group. The causes of mortality were cardiac failure in 15 (35.71%) patients, hemorrhage in 7 (16.67%) patients, sepsis in 7 (16.67%) patients, multiple organ dysfunction in 6 (14.29%) patients, renal failure in 5 (11.9%) patients, and neurologic insufficiency in 2 (4.76%) patients.
Discussion: The mortality rate could be higher than the survival rate during ECMO applications as in our study. Knowing the causes of mortality is important to take measures.
Keywords: Extracorporeal Membrane Oxygenation (ECMO), Mortality, Survival
Introduction
Extracorporeal membrane oxygenation (ECMO) is a life support application used for an acute and reversible pulmonary or cardiac injury that could not be successfully treated with traditional treatment strategies successfully, ECMO provides necessary oxygenation of the blood out of the body and has been increasingly used in intensive care units [1,2].
Extracorporeal life support was first used as salvage treatment in the mid-20th century in cardiac arrest patients who did not respond to traditional treatments. In the following period, oxygenators and centrifuge pumps of these support devices were miniaturized. The cardiac pulmonary machine has become compact and mobile and was implanted with thin-walled cannulas through peripheral routes. This has enabled ECMO application’s widespread use [3].
ECMO devices used today are applied as venoarterial (VA) and venovenous (VV) according to the type of vein in which cannulation is performed. After oxygenation, blood from the venous system is given back to the body through the venous system with VV ECMO application. It is the VA ECMO application in which blood is taken from the venous system and given back to the body through the arterial system [2,4].
In our study, we aimed to investigate factors affecting mortality in patients using ECMO in our clinic.
Material and Methods
In this study, 74 patients over the age of 18 who underwent ECMO between 1 January 2010 and 1 January 2020 in Trabzon Ahi Evran Education and Research Hospital were evaluated retrospectively. Before the study, local ethic committee approval was taken according to the Helsinki declaration (2020/01). The inclusion criteria were patients over the age of 18 who underwent VA ECMO and VV ECMO applications. Exclusion criteria were patients under the age of 18 who underwent ECMO and those whose data could not have been obtained.
Patients were divided into two groups after ECMO support as those who survived (Group 1) and as those who ended up with mortality (Group 2). Demographic data of patients, comorbidities, APACHE-2 scores, RESP scores, ejection fraction values, indications of ECMO application, applied ECMO type (VV, VA), ECMO support durations, inotropic infusion treatments applied during ECMO support, non-ECMO support applications, complications of ECMO applications, blood products used and their quantities and early mortality rates (first 30 days) were examined and recorded. Data were reviewed retrospectively through patient files and patient information processing system.
Routine ECMO application procedure
Patients were monitored by invasive systemic arterial pressure monitoring with electrocardiography, SpO2 pulse oximetry, and radial artery cannulation preferably through a non-dominant arm. The right axillary region was opened in the patient who was scheduled for VA ECMO and arterial cannulation was performed with end-to-side anastomosis. Then, percutaneous venous cannulation was performed in the femoral vein and the patient was connected to ECMO. Distal circulation of the extremity was preserved in all patients by performing retrograde cannulation in the femoral artery. In addition, in the patient who was planned for VV ECMO, the first percutaneous venous catheter was inserted in the right jugular vein and then a percutaneous venous catheter in the femoral vein. Locations of cannulas were determined with a bedside ECHO. Time flow centrifugal pump (Jostra Rotaflow; Maquet Cardiopulmonary, Rastatt, Germany) and oxygenator (Jostra Quadrox; Maquet Cardiopulmonary, Rastatt, Germany) were used for the ECMO circuit. Before inserting cannulas into the patients, prime solution in the perfusion circuit was prepared with 1000 ml Ringer and unfractionated heparin (Koparin flakon, Koçak Farma, Turkey) was added initially.
Monitoring of the patients was performed daily, and upper and lower extremity pulses were evaluated for signs of hyper-perfusion and introduction site for signs of local bleeding and infection. All patients were monitored with a SpO2 monitor, invasive radial artery monitor, records of hemodynamic parameters, arterial blood gas monitor, daily physical examinations, and echocardiography (ECHO) investigations. Dexmedetomidine (Hipnodex flakon, Haver Farma, Turkey) infusion was started intravenously for sedation. After a bolus dose of 1 µg/kg was given intravenously to the patients, the maintenance infusion dose was administered as 0.2-0.7 µg/kg/hour. Anticoagulation was provided by unfractionated heparin (100 IU/kg), and monitored with activated coagulation time (ACT) measurements.
Criteria to separate from ECMO
Criteria to separate from ECMO were determined as stabilization of hemodynamic parameters, SvO2 level >70%, Htc between 28-30, normal lactate level, sufficient urinary output, and absence of bleeding or tamponade. Echocardiography examination before the separation showed that the left ventricular ejection fraction (EF) was >30%, and left ventricular distension and severe tricuspid insufficiency were absent. Decanulation in percutaneous ECMO applications was achieved by performing surgical repair of artery and vein used in femoral exploration under local anesthesia in extubated and under sedation in intubated patients.
Statistical Methods
Statistical analyzes of the collected data were performed with IBM SPSD 25 program. In the comparisons of survival and mortality groups, the Mann-Whitney U test was used to compare mean values and Fisher’s exact test to compare frequencies. In the analysis, the significance limit was determined as 0.05.
Results
Of the 74 ECMO patients who were included in the study, 43 (58.11%) were male and 31 (41.89%) were female. VA ECMO was applied to 60 (81.08%) and VV ECMO to 14 (8.92%) patients. Indications for VA ECMO were the failure of cardiopulmonary bypass after cardiac surgery in 34 (56.67%) patients, cardiogenic shock in 14 (23.33%) patients, cardiac arrest after drug intoxication in 5 (8.33%) patients, bridge treatment in 4 patients who were scheduled for heart transplantation (6.67%), and peripartum cardiomyopathy in 3 (5%) patients. Indications for VV ECMO were pulmonary failure due to acute respiratory distress syndrome and pneumonia in 12 (85.71%) patients, and pulmonary emboli in 2 (14.29%) patients. Out of all cases, 32 (43.24%) survived and 42 (56.76%) ended up with mortality. Demographic data of groups and comorbidities before the ECMO procedure are shown in Table 1.
Comparisons of data from groups during ECMO applications are shown in Table 2.
Causes of mortality were cardiac failure in 15 (35.71%) patients, hemorrhage in 7 (16.67%) patients, sepsis in 7 (16.67%) patients, multiple organ dysfunction (MODS) in 6 (14.29%) patients, renal failure in 5 (11.9%) patients, and neurologic insufficiency in 2 (4.76%) patients.
Discussion
ECMO is one of the most important treatment methods for resistant pulmonary and cardiac failure today. The operating principle of ECMO is to take blood with a cannula applied to a large vessel through percutaneous and surgical ways, oxygenate it on the artificial membrane, and give it back to the patient [5,6].
In adult patients, ECMO treatment is performed as VA and VV ECMO. Their indications are different. The indications of VA ECMO are cardiogenic shock (acute myocardial infarction, myocarditis), inability to separate from cardiopulmonary bypass after cardiac surgery despite conventional treatments (fluid resuscitation, vasopressor, inotropic), deep cardiac arrest due to drug intoxication, cardiogenic shock secondary to right ventricular failure after pulmonary embolism, bridge treatment in patients awaiting heart transplantation, graft failure after heart transplantation and cardiogenic shock secondary to acute allograft rejection [6,7]. The indications for VV ECMO are end-stage pulmonary disease secondary to chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchiectasis and cystic fibrosis, pneumonia, graft failure after lung transplantations, pulmonary hypertension, pulmonary embolism, smoke inhalation, meconium aspiration and respiratory arrest [7,8]. In our study, the indications of VA ECMO were inability to separate from cardiopulmonary bypass after cardiac surgery, cardiogenic shock, cardiac arrest due to drug intoxication, bridge treatment in patients awaiting heart transplantation, peripartum cardiomyopathy, while the indications of VV ECMO were pulmonary failure due to acute respiratory distress syndrome, pneumonia and pulmonary embolism. These are in parallel to the literature.
Like all interventional procedures, in patients undergoing ECMO, it is important to determine mortality rates and factors affecting mortality. In our study, the 30-day mortality rate was 56.76%. In studies in the literature, the reported mortality rate (55-84%) was similar to our study [9-13].
In studies, the age of the patient was determined as an important factor for mortality, and as the mean age increased, mortality also increased. In addition, it has been reported that when these surviving patients are admitted to intensive care units, the APACHE 2 scores are lower [14,15]. In our study, we determined that age and APACHE 2 score affect mortality, and as these two figures decreased, mortality rate also decreased (Table 1).
Comorbidities accompanying ECMO applications also affect mortality. While coronary artery disease, diabetes mellitus, renal failure, and obesity are reported to be related to mortality, hypertension, and chronic obstructive pulmonary disease are also risk factors [9,10,16]. In both groups, the most common comorbidities were coronary artery disease, hypertension, and diabetes mellitus. There was no statistically significant difference when the two groups were compared in terms of comorbidities (Table 1).
RESP score which was developed to predict survival during ECMO was determined to be statistically significantly higher in the mortality group (Table 1). In the study by M. Schmidt et al, a similar result was obtained [17].
In our study, rates of ICU admission and ECMO duration were found to be lower in the survival group when compared to the mortality group (Table 2). Of course, these durations vary from patient to patient. The important thing is to allow the patient to spend enough time connected to the ECMO device to let the lung and heart recover adequately. In the patient group whose management is very difficult and complicated, early separation from the ECMO device might cause unfavorable outcomes.
ECMO application is a valuable treatment modality in patients who develop low cardiac output syndrome after cardiac surgery, and who have heart failure with very low ejection fraction values in intensive care units. With the help of ECMO, myocardial injury is a result of high dose inotropic agent use by providing circulation support early. In the literature, it has been reported that increased contractility and temporary improvement in cardiac performance due to the use of inotropic agents might lead to increased myocardial energy consumption, perfusion – contraction mismatch with increased anaerobic glycolysis, myocardial necrosis, and, as a result, the risk of progression to heart failure [18]. Thus, it is possible to associate the use of high dose inotropic before and after ECMO with heart failure and increased mortality. In our study, there was a lower need for inotropic agents in surviving patients, and noradrenalin use in the mortality group was statistically significantly higher (Table 2).
There are conflicting results in the literature on the usefulness of simultaneous intra-aortic balloon pump (IABP) use with ECMO. Brechot N et al noted in their study that there was a significant decrease in radiographic findings of pulmonary edema and shorter use of mechanical ventilation compared to VA ECMO alone, and concluded that combined IABP-ECMO use had some favorable results [19]. In a retrospective study with a large patient population size in the literature, it was reported that IABP does not affect survival [20]. In our study, simultaneous use of IABP was examined but there was no significant difference between groups in terms of IABP use (Table 2).
ECMO flow is reported as another important parameter affecting mortality in the literature. According to the results of a study, it was reported that the high flow of ECMO especially in the first 24th hour is associated with mortality [21]. In our study, when the patients were evaluated in terms of ECMO flow, ECMO flow in the 24th hour was statistically significantly faster in the mortality group (Table 2).
In ECMO applications, hemorrhage is a common complication. In particular, bleeding is one of the leading causes of mortality [22,23]. In addition, it was reported that the use of blood products is associated with mortality [9]. In our study, the use of blood products and thrombocyte suspension was found to be statistically significantly higher in the mortality group (Table 2). Another hematologic complication of ECMO that increases use of blood products and bleeding is thrombocytopenia. It was reported in the literature that thrombocytopenia could be detected in patients already admitted to intensive care units and is associated with the risk of bleeding and mortality [24]. In our study, thrombocytopenia and associated bleeding rate were higher in the mortality group (Table 3).
MODS and myocardial failure are also other important causes of mortality. In the study by Rastan AJ et al, the most common cause of mortality was reported as acute myocardial failure [9]. In another study, it was MODS [13]. In our study, cardiac failure, hemorrhage, sepsis, and MODS were found to be causes of mortality.
The limitations of our study were that the number of patients was small and it was retrospective in nature.
Conclusion
ECMO application is an important supportive treatment method for pulmonary and cardiac failure. During this application, mortality could reach higher rates than survival, as in our study. Predicting the causes of mortality and knowing the risks of encountering these is important to take necessary measures. Further prospective studies with more patients are needed in this field.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Gönül Erkan, Ahmet Eroğlu. Investigations of factors affecting mortality in our ECMO (Extracorporeal membrane oxygenation) applications. Ann Clin Anal Med 2022;13(Suppl. 2):S111-115
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Contrary to popular belief; Is placenta accreta spectrum more innocent than uterine atony?
Yunus Emre Purut 1, Fedi Ercan 2, Mehmet Murat İsikalan 3, Selcuk Eren Canakci 4, Niyazi Alper Seyhan 2, Haydar Kaya 5
1 Department of Obstetrics and Gynecology, Van Training and Research Hospital, Van, 2 Department of Obstetrics and Gynecology, Faculty of Medicine, Adnan Menderes University, Aydin, 3 Department of Obstetrics and Gynecology, Faculty of Medicine, Adiyaman University, Adiyaman, 4 Department of Emergency, Faculty of Medicine, Adnan Menderes University, Aydin, 5 Department of Obstetrics and Gynecology, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey
DOI: 10.4328/ACAM.21426 Received: 2022-10-02 Accepted: 2022-10-19 Published Online: 2022-10-19 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S116-120
Corresponding Author: Fedi Ercan, Department of Obstetrics and Gynecology, Faculty of Medicine, Adnan Menderes University, 09010, Aydin, Turkey. E-mail: fediercan@gmail.com P: +90 505 895 53 09 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2175-5405
Aim: Peripartum hysterectomy is characteristically a life-saving process used in cases of massive and unresponsive postpartum haemorrhage. The two most common indications are uterine atony and placenta accreta spectrum. This study aims to compare the demographic characteristics and peripartum results of patients who underwent peripartum hysterectomy due to uterine atony and placenta accreta spectrum.
Material and Methods: This is a retrospective cross-sectional study comparing pregnant women who underwent peripartum hysterectomy for uterine atony and placenta accreta spectrum. At the Sanliurfa Training and Research Hospital, all peripartum hysterectomy cases were researched from patients’ files and the hospital’s electronic patient information system retrospectively for 9 years from 2010 to 2019.
Results: A total of 127 patients were included in the study, 68 in the uterine atony group and 59 in the placenta accreta spectrum group. Estimated blood loss and excessive blood loss were found to be higher in the uterine atony group (1395 vs 675 ml, p <0.001; 29% vs 13%, p = 0.014, respectively). Also, the rate of patients receiving platelet transfusions was significantly higher in the uterine atony group (11 vs 0, p = 0.001).
Discussion: Although increasing cesarean rates increase in PAS cases, UA remains the most common cause of PH cases. On the other hand, UA cases may create a more risky clinical situation than PAS patients in terms of the amount of bleeding, the need for blood transfusion and complications that may lead to death, due to their unpredictable nature. The elective management of PAS cases with experienced surgical multidisciplinary teams may cause this.
Keywords: Peripartum Hysterectomy, Placenta Accreta Spectrum, Postpartum Hemorrhage, Uterine Atony
Introduction
Peripartum hysterectomy (PH) is characteristically a life-saving process used in cases of massive and unresponsive postpartum hemorrhage. Emergency PH is a procedure performed during delivery or within 24 h after delivery [1]. The incidence of PH has been reported as 0.13 to 5.38 per 1000 deliveries [2]. Uterine atony (UA) and uterine rupture are the most widespread indications of PH in undeveloped countries [3, 4], whereas placenta accreta spectrum (PAS) is the most frequent indication in developed countries. In recent years, abnormal placentation, which is likely related to the increasing rates of caesarean section, has become the most common cause of PH [1, 5].
Despite considerable medical and surgical progress over the years, maternal morbidity or mortality due to postpartum haemorrhage remains an important issue worldwide because of associated complications, which may include massive transfusion and its consequences, intraoperative complications, postoperative morbidity, and even maternal mortality [6, 7]. Patients on whom UA is performed are near-miss cases. However, most of the time, PAS cases are operated on under elective conditions, and therefore obstetricians are aware of what might happen.
This study aims to compare the demographic characteristics and peripartum results of patients who underwent PH due to UA and PAS.
Material and Methods
This retrospective cross-sectional study compared pregnant women who underwent PH for UA and PAS. At the Sanliurfa Training and Research Hospital, all PH cases were retrospectively researched from patients’ files and the hospital’s electronic patient information system for nine years from 2010 to 2019. Sanliurfa is located in the underdeveloped southeastern Anatolia region of Turkey. According to the Turkey Statistical Institute data, the city with the highest birth rate in Turkey is Sanliurfa (available at: https://tuikweb.tuik.gov.tr/UstMenu.do?metod=temelist). Most of the births in Sanliurfa take place in our hospital. Further, Sanliurfa is the city where the refugee migration that occurred after the Syrian civil war that started in 2011 was the most intense.
Ethical approval for our study was obtained from the Harran University Ethics Committee on 25 July 2019, with the registration code E.31699. The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki. Pregnant women who underwent PH at the time of delivery (cesarean section or vaginal) or within 24 h after delivery were included. Pregnancies over 24 gestational weeks were enrolled in the study. Pregnant women less than 24 weeks, postpartum hemorrhage developing 24 hours after birth, patients diagnosed with PAS during surgery, patients whose data could not be fully accessed, and PAS patients who were urgently operated on were excluded from the study. The diagnoses of all patients with PAS were histopathologically confirmed. Patients without a histopathological diagnosis were excluded from the study. As a result, two patient groups,the UA group and the PAS group, were formed (Figure 1, the study flowchart).
The ultrasonographic diagnostic standards for PAS are irregular lacunae, a defect of the retroplacental myometrial zone, and turbulent flow. Physical and ultrasound examinations (with Doppler) were performed antenatally by an obstetrician who worked in the obstetrics and gynecology emergency service. A hysterectomy was performed by another operating surgeon. We prepared four units of red blood cell (RBC) suspension and fresh frozen plasma (FFP) for each PAS patient. A vertical incision was performed in patients with known PAS, whereas a Pfannenstiel incision was made for those with UA.
The patients’ data included in the study were obtained from electronic records, and any missing data were retrieved from the conventional file archive. Ages, weights, parity, number of previous caesarean sections, gestational age at delivery, pre-and postoperative hemoglobin (Hbg) values, duration of operation, RBC transfusion, FFP transfusion, platelet transfusion, duration of hospital stay, estimated blood loss volume (EBLV), excessive blood loss, and complications of the two groups were compared.
From the Hbg results measured 7 days before giving birth, the Hbg values closest to the birth date were accepted as preoperative Hbg. Postoperative control Hbg values were evaluated 24 hours after surgery. Women who had five or more deliveries were defined as grand multipara. Blood transfusion indication was set according to the patient’s vital signs, perioperative estimated bleeding amount, intraoperative Hbg levels, or postoperative Hbg level below 7 g/dL. Patients who received a blood transfusion during cesarean section or up to 24 hours postoperatively were considered as “transfusion patients”. Patients who were given perioperative or postpartum additional oxytocin, misoprostol, methylergonovine, or carbetocin and who underwent uterine massage were categorised as patients with UA. Hysterectomy was performed in patients who did not respond to these medical treatments and compression sutures in the UA group. Hysterectomy was performed directly in unstable patients who completed their fertility.
EBLV was calculated using a method previously defined by Staffort et al., which utilizes maternal height and weight, as well as preoperative and postoperative haematocrit values [8]. In this calculation, pregnancy blood volume was calculated first (0.75 ([maternal height (inches) × 50] + [maternal weight in pounds × 25]). Then, the percentage of blood volume lost was calculated with the formula: predelivery hematocrit – postdelivery hematocrit)/predelivery hematocrit. EBLV is calculated as: calculated pregnancy blood volume ×percent of blood volume lost. Excessive blood loss was defined as blood loss ≥ 1500 ml within 24 hours after birth [8].
Statistical analysis
Statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS) 16.0 for Windows software program. Descriptive data were rendered as mean ± standard deviation, median (minimum, maximum), or n (%). A p-value < 0.05 was accepted as statistically significant.
The G * Power 3.1 program (Erdfelder, Foul and Buchner, Dusseldorf, Germany) was used for post hoc power analysis. The α error probability, effect size, and power of the study were 0.05, 0.5, and 0.87, respectively.
Results
In the study period, the total number of births was 237,586 at the Sanliurfa Training and Research Hospital. In the same period, 180 PHs were performed. The indications of PHs performed during the study period are shown in Figure 2.
Fifty-three patients who did not meet the inclusion criteria were excluded from the study. A total of 127 patients were included in the study, 68 in the UA group and 59 in the PAS group (flowchart is shown in Figure 1).The mean ages of the women were 33.5 ± 7.2 and 34.0 ± 5.6, respectively. The number of previous cesarean sections was significantly higher in the PAS group (median values 0 vs 2, p <0.001). We observed that delivery occurred in earlier weeks in the PAS group (median values 37.0 vs 39.0 weeks, p <0.001). Other demographic characteristics of the groups are shown in Table 1.
There was no significant difference between the groups in terms of preoperative Hbg values, the need for RBC transfusion, and the duration of the operation. However, postoperative Hbg values were lower in the UA group (9.3 vs. 9.7 g/dL, p = 0.012). Also, EBLV and excessive blood loss were found to be higher in the UA group (1395 vs. 675 ml, p <0.001; 29% vs. 13%, p = 0.014, respectively). In contrast, the rate of patients receiving platelet transfusions was significantly higher in the UA group (11 vs. 0, p = 0.001). The comparison of the UA group and PAS group is shown in Table 2.
Surgical complications occurred in 22 (17.3%) of the patients. There was no significant difference between the total surgical complication rates of the groups. Although DIC was observed more frequently in the UA group (5 vs. 0, p = 0.034), bladder injury was more common in the PAS group (8 vs. 0, p = 0.002) (Table 3). One mother died in the UA group.
Discussion
During this study, 180 patients underwent PH out of 237,586 deliveries. The incidence of PH was observed as 0.75 per 1000 deliveries, compared to the incidences reported for the United Kingdom and Italy (0.41 and 2.2 per 1000 deliveries, respectively) [9, 10]. The most common indication for PH in this study was UA (37.8%), whereas the second most common cause was PAS (32.8%). UA is indicated as the most common cause of PH in underdeveloped countries [3], unlike in developed countries, where PAS is the most common [11, 12]. In this context, there is a difference between eastern and western Turkey. Studies conducted in eastern Turkey are consistent with the data in the least developed countries [6], whereas findings in western Turkey are consistent with those of developed countries [13]. Our findings were consistent with data from less developed countries because the city where our hospital is located is in a less developed part of Turkey.
EBLV and excessive blood loss were significantly higher in the UA group in this study. Additionally, there was no significant difference between preoperative Hgb levels, but the postoperative level was found to be significantly lower in the UA group compared with the PAS group (median 9.3 g/dL vs 9.7 gr/dL, p=0.012). The most important reason for this may be that despite the unpredictable process of UA, PAS patients are managed with clearer boundaries. There are differences in the processes for deciding PH for pregnant women. Patients with UA often experience a prolonged, useless period of conservative treatment before proceeding to laparotomy (or relaparotomy, if caesarean delivery has been performed) and hysterectomy if necessary. The decisions made in this process are often not perfect, and the management of this period among patients is often heterogeneous. Compression suture and uterine or hypogastric artery ligation can be applied to protect the uterus, especially in young patients. Often, if these methods fail, PH becomes the last option [14]. Unlike in PAS patients, coagulopathy, hypovolemia, tissue hypoxia, and hypothermia can be experienced more intensely in UA patients due to this situation [15]. By contrast, in PAS patients, the bladder may adhere to the old hysterotomy line, and the expanded lower uterine segment may make surgical plans difficult. However, patients with PAS often start surgery with an experienced surgical and anaesthesia team and a prior decision on PH. This provides a more predictable process in PAS patients.
Transfusion of blood and blood products is often necessary and life-saving in PH cases. In a recent multicentric study, the need for blood transfusion in PH patients due to UA and PAS was found to be 49.2% and 77.8%, respectively [16]. In a systematic review that included 7001 PAS cases, blood transfusion was required in 46.9% of the patients (95% CI 34.0-59.9) [17]. In our study, 47.1% and 47.5% of the patients in the UA and PAS groups, respectively, received blood transfusions. There was no significant difference between the two groups in terms of need for blood transfusion. However, platelet transfusion was significantly higher in the UA group. Although this was not statistically significant in the UA group, it may be related to the development of more DIC complications. By contrast, EBLV and excessive blood loss were more common in the UA group, and this may increase the need for platelet transfusion. Platelet transfusion need is closely related to the presence of massive blood loss and the development of DIC [18].
The most severe complication of PH is maternal death, and its incidence has been reported as ranging from 0 to 12.5 % [19]. However, high rates of up to 59% have been reported in emergency cases [20]. One maternal death occurred in the patients included in the study (0.78%). This patient was in the UA group. The reason for the low rate may be that the patients in our study group consisted of only UA and PAS patients. However, PAS cases were patients who were operated on under elective conditions, and this may contribute to this result.
Complications, such as postoperative bleeding, wound infection, urinary tract injury, thrombosis-related conditions, DIC, and relaparotomy, may cause maternal morbidity [21]. Emergency procedures are associated with a higher rate of complications than planned procedures [22]. In our study, bladder injury was significantly more common in the PAS group. In PH performed due to PAS, the bladder frequently adheres to the old hysterotomy line, which is an expected result of this situation. DIC was significantly higher in the UA group, which may be related to the adverse effects on hemodynamic and coagulation parameters of the ongoing bleeding during interventions to protect the uterus before a PH decision is made in the UA group. Additionally, the operations of PAS patients are frequently performed by a team that includes experienced anaesthetists and obstetricians. The primary surgeon usually has substantial experience in pelvic surgery and hysterectomy. This allows for much better management of the patient in case of unexpected bleeding.
The most important risk factor for the development of PAS is placenta previa after previous cesarean delivery. In a prospective study in which 723 women with placenta previa gave birth by caesarean section, the frequency of PAS increased with the increasing number of cesarean delivery [23]. In our study, the number of previous cesarean sections was significantly higher in the PAS group.
However, the gestational week at birth was significantly smaller in the PAS group. The optimum gestational age for planned delivery in PAS patients is controversial, and high-quality data are lacking. For stable (no bleeding or preterm labour) patients, the American College of Obstetricians and Gynecologists recommends a planned delivery between 34–35 + 6 weeks [24]. UA often develops after a term birth. The smaller birth weeks of PAS patients are a result of this situation.
The strength of our study is that PH cases emerging from a large birth pool covering a long period were evaluated in a single centre. However, we were limited by the retrospective nature of the study. Another limitation is that we did not classify the PHs as supracervical or total. In one large study, total hysterectomy was associated with more bladder, vein, and ureter injuries and transfusions. Supracervical hysterectomy is associated with higher reoperation and perioperative mortality rates [25]. Further, interventions applied to patients in the UA group before PH are not standard, and this may cause bias.
Conclusion
Although increasing cesarean rates increase PAS incidence, UA remains the most common cause of PH cases. UA cases may create a riskier clinical situation than PAS patients in terms of the amount of bleeding, the need for blood transfusion, and complications that may lead to death due to their unpredictable nature. The elective management of PAS cases with experienced surgical multidisciplinary teams may explain this difference.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Yunus Emre Purut, Fedi Ercan, Mehmet Murat İsikalan, Selcuk Eren Canakci, Niyazi Alper Seyhan, Haydar Kaya. Contrary to popular belief; Is placenta accreta spectrum more innocent than uterine atony? Ann Clin Anal Med 2022;13(Suppl. 2):S116-120
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Comparison of anterior uterocervical angle in unexplained primary infertile and primigravid cases
Fırat Kaya 1, Gulchin Babayeva 2, Yunus Emre Purut 1, Abdulaziz Gul 3
1 Department of Obstetrics and Gynecology, University of Health Sciences, Van Training and Research Hospital, Van, 2 Department of Obstetrics and Gynecology, Gaziosmanpasa Ekotom Medical Center, Istanbul, 3 Department of Obstetrics and Gynecology, Van Yüzüncü Yıl University, Van, Turkey
DOI: 10.4328/ACAM.21430 Received: 2022-10-03 Accepted: 2022-10-19 Published Online: 2022-10-19 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S121-126
Corresponding Author: Yunus Emre Purut, Department of Obstetrics and Gynecology, University of Health Sciences, Van Training and Research Hospital, Van, Turkey. E-mail: purutemreyunus@hotmail.com P: +90 505 230 05 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5779-3847
Aim: The aim of this study was to investigate the hypothesis that narrow angle may prevent sperm passage and thus cause infertility by comparing anterior uterocervical angle (A-UCA) in patients with unexplained infertility and primigravid cases at early gestational week.
Material and Methods: This study included 126 cases, including 75 cases of unexplained infertility and 51 cases with a diagnosis of primigravid at early gestational week, who applied to the Van Yuzuncu Yil University Gynecology and Obstetrics Clinic between February 2021 and October 2021. A-UCA values of infertile cases were reviewed. Primigravid cases with β-hCG values of <1000 mIU/ml were included in the study. A-UCAs were measured with transvaginal ultrasonography and while the bladder was empty.
Results: In our study, no statistically significant difference was found between the increase in β-hCG value and A-UCA value in the pregnant group (p>0.05).
Discussion: It was found that the A-UCA did not show a significant difference between primigravid cases at early gestational weeks and unexplained primary infertile cases.
Keywords: Anterior Uterocervical Angle, Infertility, Unexplained Infertility
Introduction
Infertility is defined as the absence of pregnancy after 12 months of unprotected intercourse. This can be seen in 10-15% of couples [1]. Approximately half of the infertile couples can become pregnant in the second year of the trials without treatment. Although infertility treatment has made great progress, it is not possible for couples to have babies for some reasons that are still unexplained today, and this occurs in approximately 17% of infertile couples [2].
Unexplained infertility is defined as the absence of any pathology in the basic evaluation (sperm analysis, ovulation tests, hysterosalpingography, revealing there is no pathology in the cavity and tuba) in couples who cannot achieve pregnancy after 1 year of unprotected sexual intercourse. With the addition of evaluation with ultrasonography to the basic evaluation, myoma uteri, endometrioma, and decreased ovarian reserve findings can be detected in some of the couples with unexplained infertility [3, 4]. Problems in tubal passage, mild ovulatory dysfunction, luteal phase deficiency, and implantation abnormalities (e.g., decreased expression of essential endometrial cell surface receptor protein αvβ3 integrin, or low endometrial perfusion, etc.) are the factors that can lead to infertility although they cannot be explained by basic infertility tests [5]. Apart from these, factors that solely cause a minimal decrease in infertility potential being present in both of the partners can also cause unexplained infertility. It is not known in advance whether sperm/zona pellucida penetration can occur successfully since a semen analysis cannot fully demonstrate the functional capacity of sperms. This leads to the evaluation of some infertile cases whose etiology is male factors in the unexplained infertility group [6].
Anterior uterocervical angle is the angle formed between the longitudinal line connecting the internal and external cervical os and the longitudinal line connecting the anterior wall of the uterus and the internal cervical os. The importance of this angle in the field of gynecology and obstetrics has been increasing in recent years. Studies conducted in recent years suggest that narrow A-UCA in individuals with unexplained infertility may play a role in the etiology by preventing sperm passage; in addition, it was suggested that a wide angle may be effective in the etiology of preterm labor and cerclage success, while a narrow angle may be effective in dysmenorrhea and IVF success [4, 6-8].
In our study, we aimed to compare the A-UCA values in unexplained infertile cases and individuals at early gestational week (β-hCG<1000 mIU/ml), between 18-35 years of age, with a body mass index between 18-25, without any known comorbidities, who are non-smokers, and those who have not previously undergone gynecological surgery.
Material and Methods
A total of 126 patients included in the study consisted of 75 unexplained infertile cases, and 51 primigravid cases at early gestational week (β-hCG<1000 mIU/ml), who were aged between 18-35 who applied to the Obstetrics and Gynecology outpatient clinic of Van YuzuncuYil University Faculty of Medicine, Department of Obstetrics and Gynecology between February 2021 and October 2021, with no known comorbidities and no history of previous surgery, with a BMI of 18-25 kg/m2 range, no smoking history, and not meeting any of the exclusion criteria of the study.
ESHRE (European Society of Human Reproduction and Embryology) and ASRM (American Society for Reproductive Medicine) guidelines were taken into consideration when making the unexplained infertility diagnosis. Informed consent was obtained from all patients in the study group. All patients were examined with a detailed anamnesis. Patients with anatomical, thrombophilia, genetic and immunological factors that would exclude the diagnosis of unexplained infertility and patients who were obese, had previous gynecological operation history and secondary infertility were excluded from the study. Unexplained infertile cases documented by ultrasonographic, radiological, hormonal examination and semen analysis, and primigravid cases at early gestational week (β-hCG˂1000 mIU/ml) were included in the study. Since it is known that the cervical angle changes with the progression of pregnancy, the β-hCG value in primigravid cases was limited to 1000 mIU/ml in order to minimize the measurement differences that may occur accordingly.
Age, height, weight, and body mass index (BMI) were measured and recorded in both patient groups. In some of the cases, laboratory and imaging results performed in the health center they previously applied were evaluated and recorded. In the menstrual history, cycle lengths, irregularities, dysmenorrhea were questioned and recorded, if any. All patients included in the study underwent detailed general physical and gynecological examination, and ultrasound and hysterosalpingography were preferred for uterine anomalies. FSH, LH, TSH, prolactin levels on the 2nd day and serum progesterone levels on the 21st day of menstruation in unexplained infertile cases, sperm analysis of the spouses and B-hCG values in primigravid cases were subjected to a detailed examination. Then, the A-UCA angles of the two groups were measured with the same USG device, while the bladder was empty, in the gynecological position, and transvaginally by the same person, and recorded (Figure 1).
Our study was submitted to Van Yuzuncu Yil University Clinical Research Ethics Committee and approved on 03.31.2021 with the number 18.
Statistical analysis
In the descriptive statistics of the data, mean, standard deviation, median, lowest, highest, frequency, and ratio values were used. The distribution of the variables was tested using the Kolmogorov-Smirnov test. Quantitative independent data were analyzed using the Mann–Whitney U test. Spearman’s correlation coefficient was used for correlation analysis. SPSS 27.0 program was used in the analyses.
Results
Anterior uterocervical angles were measured in all cases in the range of 66°-138°. The narrowest angle in unexplained infertility cases was 66°, the widest angle was 120°, the mean was (99.0±10.9) degrees; the narrowest angle in the primigravid group was 73°, the widest angle was 138°, and the mean was (100.3±12.8) degrees (Figure 2).
The mean age of the patients included in the study was 25 years; the mean age was 26.0 in the infertile patient group, while it was 24.0 years in the early pregnancy group. Demographic characteristics of the subjects are presented in Table 1.
No significant correlation was observed between the increase in β-hCG value and A-UCA value in the primigravid group (p >0.05). A-UCA angles were found to be narrower in the unexplained primary infertile group. However, there was no statistically significant difference between the A-UCA values of the two groups compared to the cases in the primigravid group (p > 0.05) (Table 3).
Discussion
Although it has not been studied enough in the literature, the importance of the angle between the uterus and the cervix has been the subject of some recent studies. Studies have shown that a narrow anterior uterocervical angle may prevent sperm passage and thus complicate pregnancy, increase cerclage success, increase dysmenorrhea, and especially risk of preterm birth with a wide angle has been particularly emphasized [5, 6, 8-11].
In a prospective study by Madendag et al., in the angle measurement of 50 unexplained infertile cases and 30 primigravid fertile cases at early gestational week, the anterior uterocervical angle was wider in the primigravid group than in the unexplained infertile group, and based on this result, it was concluded that narrow A-UCA might be associated with unexplained infertility etiology [8]. On the other hand, in our study with a larger participant group, there was no significant difference between the unexplained infertile group and the primigravid group in terms of A-UCA values, and no correlation was found between angle and infertility.
In another retrospective study conducted by Knight et al., the effectiveness of anterior uterocervical angle in cerclage success was investigated [9]. For this purpose, 142 pregnant women who had cerclage over a 5-year period were retrospectively reviewed; cervical characteristics, cervical length, cerclage levels, and volume of becoming funnel-shaped were recorded with endocervical USG, and their anterior uterocervical angles were measured before cerclage, immediately after cerclage, and just before delivery. Cerclage was considered unsuccessful in deliveries before 36 weeks. At the end of the study, cerclage was unsuccessful in 38% of cases. It was revealed that cerclage failure increased with the expansion of the anterior uterocervical angle [6]. Again, in a study conducted by Sahin et al. on 150 patients diagnosed with primary dysmenorrhea and 50 healthy volunteers, after grouping the patients by pain severity, it was concluded that there was an inverse relationship between pain severity and anterior uterocervical angle, and the angle was narrower in patients with severe pain, the angle was different among those with mild, moderate and severe pain, and based on this result, it was concluded that a narrow anterior uterocervical angle may play a role in the etiology of dysmenorrhea [11]. Although these studies used a similar method to our study during the measurement of A-UCA, it is obvious that the studies were conducted for different purposes and with different case groups.
There are a limited number of studies on the relationship between anterior uterocervical angle and fertility. We believe that further extensive and numerous studies on this topic are required.
Conclusion
In a similar study conducted with lower β-Hcg values and smaller number of participants, it was suggested that the anterior uterocervical angle was different between two patient groups, that A-UCA was narrower in the infertile group, and therefore it could have played a role in the etiology of unexplained infertility. As a result of our study, there was no statistically significant difference between the primigravid cases in the early gestational week and unexplained infertile cases for the anterior uterocervical angle, which is thought to play a role in the etiology of unexplained infertility, and we think that more randomized controlled studies are necessary in this regard.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Cetin E, Siblini H, Al-Hendy A. What Is the Mechanism of Poor Endometrial Proliferation in Patients with Unexplained Infertility After Clomiphene Citrate Treatment? J Clin Endocrinol Metab. 2021;106(11): e4776–e77.
2. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007;22(6):1506-12.
3. Speroff L, Fritz MA, editors. Female infertility clinical gynecologic endocrinology and infertility. Philadelphia: Lippincott Williams &Wilkins; 2011.p.1185- 9.
4. Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand. 2017;96(6):659-67.
5. Reindollar RH, Regan MM, Neumann PJ, Levine BS, Thornton KL, Alper MM, et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and Standard treatment (FASTT) trial. Fertil Steril. 2010;94:888–99.
6. Tollner TL, Venners SA, Hollox EJ, Yudin AI, Liu X, Tang G, et al. A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med. 2011;3(92):92ra65.
7. Col Madendag I, Eraslan Sahin M, Madendag Y, Sahin E, Demir MB, Ozdemir F, et al. Effect of the anterior uterocervical angle in unexplained infertility: a prospective cohort study. J Int Med Res. 2020;48(4). DOI: 10.1177/0300060519893497.
8. Dziadosz M, Bennett TA, Dolin C, West Honart A, Pham A, Lee SS, et al. Uterocervical angle: a novel ultrasound screening tool to predict spontaneous preterm birth. Am J Obstet Gynecol. 2016;215(3):376.e1-7.
9. Knight JC, Tenbrink E, Sheng J, Patil AS. Anterior uterocervical angle measurement improves prediction of cerclage failure. J Perinatol. 2017;37(4):375-9.
10. Singh PK, Srivastava R, Kumar I, Rai S, Pandey S, Shukla RC, et al. Evaluation of Uterocervical Angle and Cervical Length as Predictors of Spontaneous Preterm Birth. Indian J Radiol Imaging. 2022;32(1):10-5.
11. Sahin ME, Sahin E, Madendag Y, Madendag IC, Tayyar AT, Özdemir F, et al. The Effect of Anterior Uterocervical Angle on Primary Dysmenorrhea and Disease Severity. Pain Res Manag. 2018;2018:9819402.
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Fırat Kaya, Gulchin Babayeva, Yunus Emre Purut, Abdulaziz Gul. Comparison of anterior uterocervical angle in unexplained primary infertile and primigravid cases. Ann Clin Anal Med 2022;13(Suppl. 2):S121-126
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Flexion contracture in 2-5 digits following hypothenar flap
Harun Köse 1, Serhat Ekrem 1, Ahmet Sağır 2, Ersen Türkmen 3, Kadir Ertem 1
1 Department of Orthopedic and Trauma Surgery, Faculty of Medicine, Inonu University, Malatya, 2 Department of Orthopedic and Trauma Surgery, Kadirli State Hospital, Osmaniye, 3 Department of Orthopedic and Trauma Surgery, Polatli State Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20925 Received: 2021-12-16 Accepted: 2022-09-12 Published Online: 2022-09-28 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S127-129
Corresponding Author: Harun Köse, Department of Orthopedic and Trauma Surgery, Inonu University, Faculty of Medicine, Bulgurlu Neighborhood Elazig Road 15th km No:4 44280, Malatya, Turkey. E-mail: harunkose925@gmail.com P: +90 506 206 18 96 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6549-4166
We aimed to discuss a case of severe flexion contractures affecting 2nd-5th fingers as a late complication of a hypothenar skin flap that we applied to a patient with a fingertip injury that ended with tissue loss in the tip of the fifth finger of the right hand. Soft tissue defects of the little finger are challenging, especially when a bone, tendon or vascular pedicle is exposed because of trauma. The hypothenar random flap is easy to harvest and has a good color and texture match to the little finger pulp. For this complication, which did not improve sufficiently with physical therapy methods, contractures were tried to be eliminated by open surgical release of the 2nd-5th fingers to the proximal interphalangeal joints.
Keywords: Hypothenar Flap, Contracture, Injury, Finger
Introduction
Fingertip amputations are the most common type of amputation of the upper extremity. There are many treatment options for fingertip amputations. Tratement method may vary widely from healing by secondary intention to replantation of the amputation, depending on the level of the amputation and the tissue components involved. The aim of the treatment is to achieve the best functional and aesthetic result with the least pain in the shortest time.
The thenar flap is a satisfactory reconstruction technique for the treatment of fingertip injuries of the index and middle fingers, and the hypotenar flap is a satisfactory reconstruction technique for 4th and 5th fingertip injuries. As in this study, this flap is reliable and provides adequate coverage to the missing finger pulp. Flap sensitivity is good. Transferring a distal-based flap prevents proximal interphalangeal joint contracture and allows the surgeon to better reconstruct the outline of the distal phalanx [1].
In this case report, we present a case of flexion contracture affecting the PIP joints of the 2nd-5th fingers as a complication of hypothenar flap surgery.
Case Report
A 38-year-old male patient applied to the emergency department of our hospital on 31.05.2019 with a crush-laceration injury involving the distal end of the fifth finger of the right hand. The injury related to a wrap and pull with a rope resulted in a total amputation of the fingertip. Hypothenar random flap, which is a preferred 2-stage method for fingertip injury of the little finger, was applied to the patient. The skin defect in the hypothenar region was closed with a full-thickness skin graft taken from the medial region of the right wrist. The graft donor area was primarily sutured. After 23 days, the hypothenar flap was separated. It was observed that the blood supply of the finger pulp was sufficient and the healing of donor areas was normal. It was noted that flexion contracture developed in the 2nd, 3rd, 4th and 5th fingers of the patient during the postoperative 28th-day follow-up (Figure 1a). Physical examination revealed a 25-degree flexion contracture at the DIP (Distal interphalangeal) joint of the 5th finger. In the PIP (proximal interphalangeal) joint, the active and passive flexion contractures at 2nd-5th PIP joints were found to be 20,30,40 and 50 degrees respectively. On 18.11.2020, contracture release surgery was planned and the skin was incised with Bruner incisions to open the flexion contractures of the 2nd-5th fingers of the right hand (Figure 1b). The volar plates in the contracted fingers were freed proximally. In addition, FDS (Flexor digitorum superficialis) tenotomy was performed on the 5th finger at the level of a3 pulley in order to overcome the contracture. Moreover, the ulnar side of the FDS tendon of the 4th digit had to be cut. Subsequently, it was observed that the fingers came to full extension passively (Figure 2). The skin was regularly closed primarily (Figure 3). Controlled active motion was started 3 days after the operation and a position-preserving night splint was recommended for 6 weeks. A preoperative consent form was obtained from the patient.
Discussion
Fingers are very important organs and various finger reconstructions have been reported. The basic goals of any fingertip reconstruction are to maintain digital length and volume, minimize aesthetic loss and preserve finger function [2]. Treatment options vary depending on the injury mechanism, defect’s size and plane, surgeon’s intention, patient’s needs, condition of the stump and the amputated part. However, there is a consensus that replantation is the best choice for maintaining the length of the finger and the normal anatomy of the nail complex, if only the amputated fragment is available, in replantable condition and well preserved [3]. The Atasoy flap, the Kutler flap, cross finger flap, thenar and hypothenar flaps, digital perforator artery flap are among the most commonly used options in emergencies [4]. These flaps require gradual operations and prolonged immobilization results in joint stiffness [5]. To the best of our knowledge, our case is the first case of multiple finger contracture after one finger flap construction. All four fingers had to be operated on to relieve joint stiffness.
Careful flap selection, preoperative planning, and patient compliance with the planned treatment are crucial in the coverage of the pulp defect, preservation of finger length, prevention of adjacent joint contracture, and minimizing donor site morbidity [6]. In our case, the patient did not follow our postoperative instructions. The patient was recommended to perform passive range of motion exercises to prevent contractures. At the 4th week visit, we detected the contractures and the patient was consulted by the physiotherapy team. The patient did not perform physio and came back to follow up at our clinic one and half year later. The flexor tenolysis was performed to release contracture.
In our study, although the patient was young, contracture developed due to a lack of communication and rehabilitation.
Conclusion
In fingertip injuries, there are many reconstructive treatment options such as V-Y advancement flap, composite graft, digital artery perforator flaps, etc. It is important to obtain an optimum functional finger for the patient, a finger that does not experience loss of fingertip sensation and that looks the closest to normal in terms of cosmetics.
In this case report, in which reconstruction of the fingertip injury was performed utilizing hypothenar flap and followed up in the flexion position for 3 weeks, it was noted that significant flexion contractures were developed not only in the 5th finger but also in the 2nd-4th fingers.
Although flexion contracture and tenderness in the proximal interphalangeal joint related to hypothenar flaps are frequently reported complications, the literature reports that severe contracture developed significantly in the non-injured fingers as in our case, which is extremely rare [7].
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Barbato BD, Guelmi K, Romano SJ, Mitz V, Lemerle JP. Thenar flap rehabilitated: a review of 20 cases. Ann Plast Surg. 1996;37(2):135-9.
2. Mitsunaga N, Mihara M, Koshima I, Gonda K, Takuya I, Kato H, et al. Digital artery perforator (DAP) flaps: Modifications for fingertip and finger stump reconstruction. J Plast Reconstr Aesthet Surg. 2010;63(8):1312-7
3. Sungur N, Kankaya Y, Yıldız K, Dölen UC, Koçer U. Bilateral V-Y rotation advancement flap for fingertip amputations. Hand (N Y). 2012;7(1):79-85.
4. Matsui J, Piper S, Boyer MI. Nonmicrosurgical options for soft tissue reconstruction of the hand. Curr Rev Musculoskelet Med. 2014;7(1):68-75.
5. Mutlu OO, Colak O, Dilber A, Bingol D, Egemen O. Complicated fingertip defects: clinical approach to their reconstruction and the flaps that can be used in emergency settings. Turk Plastik. 2019;27:14–18.
6. Gupta, Saurabh et al. Keystone Flap for Postburn Finger Flexion Contracture Release. Journal of cutaneous and aesthetic surgery. 2021;14(1):125-8.
7. Hong JP, Lee S-J, Lee H-B, Chung YK. Reconstruction of fingertip and stump using a composite graft from the hypothenar region. Ann Plast Surg. 2003; 51(1):57–62.
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Harun Köse, Serhat Ekrem, Ahmet Sağır, Ersen Türkmen, Kadir Ertem. Flexion contracture in 2-5 digits following hypothenar flap. Ann Clin Anal Med 2022;13(Suppl. 2):S127-129
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Term pregnancy after the diagnosis of benign metastasizing leiomyomatosis
Fatma Nurgül Taşgöz 1, Melih Çekinmez 2
1 Department of Obstetrics and Gynecology, University of Health Sciences, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, 2 Department of Neurosurgery, Adana City Training and Research Hospital, Adana, Turkey
DOI: 10.4328/ACAM.21151 Received: 2022-03-19 Accepted: 2022-04-19 Published Online: 2022-04-19 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S130-133
Corresponding Author: Fatma Nurgül Taşgöz, Mimar Sinan Mahallesi, Emniyet Caddesi, No:35, 16310, Yıldırım, Bursa, Turkey. E-mail: fna78@yahoo.com P: +90 224 294 40 00 F: +90 224 366 69 25 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9181-7574
Benign metastasizing leiomyomatosis (BML) is a rare entity characterized by extrauterine tumoral formation of smooth muscle cells with histologic, immunologic, and molecular features similar to uterine leiomyomas. The most common site of metastasis is the lungs, but they can spread to any site in the body. A 30-year old woman with a history of myomectomy presented with symptoms of low back pain. A Tru-cut biopsy of the 50×40-mm solid mass in the right paraspinal muscle detected on magnetic resonance imaging was diagnosed as BML, and the mass was surgically resected. A 17-mm solid nodule was detected in the upper lobe of the right lung on chest computed tomography. The patient became pregnant one year after the diagnosis. An uneventful pregnancy resulted in a live birth at 38 weeks of gestation. BML may have different clinical presentations and progression patterns, and aggressive treatments can be avoided with an individual approach.
Keywords: Benign Metastasizing Leiomyomatosis, Myomectomy, Pregnancy
Introduction
Benign Metastasizing Leiomyoma (BML) is a rare tumoral formation of smooth muscle cells without malignant features located in any tissue in the body. Although the most frequent sites of metastasis are the lungs (79.5%), the abdominal cavity, retroperitoneum, muscular tissue, bone, lymph node, blood vessels or even heart have also been reported to be affected [1]. Albeit explanations for its etiology do not go beyond theories, it mostly occurs years after myomectomy or hysterectomy performed for leiomyoma. In the review containing the largest number of patients on the subject, it was reported that the mean age at the time of the first surgery was 38.5 years, the mean age of diagnosis was 47.3 years, and the average interval between the first surgery and diagnosis was 8.8 years [2]. Due to the rarity of this disease, treatment has not been standardized. Suppression of estrogen production has been the main goal in treatment [1]. Our case is unique; the diagnosis of BML was made at a young age, shortly after the patient underwent uterine surgery, and despite the increased endogenous estrogen, the pregnancy after diagnosis was uneventful and resulted in a live birth.
Case Report
A 30-year-old woman with a history of two vaginal deliveries and a myomectomy one year ago presented to the clinic with symptoms of low back pain and a palpable mass on the right side of the spine, at the waist level. Magnetic resonance imaging (MRI) revealed the presence of a 50×40-mm mass located in the right paraspinal muscle at the L3-L4 level (Figure 1). A Tru-cut biopsy was performed with the preliminary diagnosis of schwannoma. A mesenchymal tumor, which demonstrated immunohistochemically to be positive for desmin, vimentin, smooth muscle actin (SMA), and estrogen/progesterone receptors (ER,PR), and negative for S-100 and a low tumor cell proliferation index (Ki67 index of 0-1%) was defined as leiomyoma. The low mitosis index, no evidence of anaplasia or necrosis, and minimal vascularization differentiated the lesion from leiomyosarcoma. Transvaginal ultrasound and MRI showed 25-mm type 3 and 19-mm type 4 fibroids in the uterus, and chest computed tomography (CT) revealed a 17×12-mm nodule in the upper lobe of the right lung (Figure 2). Positron emission tomography/computed tomography (PET-CT) scan showed no additional focus of metastasis except the existing lesions. The tumor in the paraspinal muscle was surgically resected (Figure 3). The patient, who could not tolerate estrogen suppression treatment with gonadotropin-releasing hormone analogs (GnRHa), became pregnant one year after the diagnosis. An uneventful pregnancy without BML-related symptoms or significant progression of the existing lesions resulted in a live birth by elective cesarean section at 38 weeks of gestation. During cesarean section, no contour irregularity and fibroids were observed on the outer surface of the uterus. In the postpartum 2nd-month transvaginal ultrasound evaluation, it was determined that the number and size of uterine myomas were constant. A chest CT scan showed that the pulmonary lesion of the patient, without any clinical pulmonary symptoms, had progressed to 27×16 mm, and there was no metastatic residual lesion in the MRI of the paraspinal lumbar muscle from where the mass was excised previously. Close surveillance of the patient continues. Written informed consent was obtained from the patient for participation and publication.
Discussion
Despite its metastatic potential, BML is a rare benign disease characterized by extrauterine multiple smooth muscle cell tumors, similar to uterine leiomyoma, seen mostly in women of reproductive age with a history of leiomyoma. The lungs are the most common site of involvement (79.5%). The majority of pulmonary BML cases present with multiple solid nodules (87%), they are often asymptomatic and found incidentally. Other less frequent metastasizing sites reported are lymph nodes, blood vessels, pelvis, muscular tissue, bone (skull, spine, femur), even pancreas and heart [2,3].
The pathologic mechanism of BML has not yet been elucidated. The fact that the majority of patients have a history of myomectomy or hysterectomy for leiomyoma suggests that there may be cardiovascular or lymphovascular spread of smooth muscle cells or direct peritoneal seeding due to surgical manipulation [3]. However, there are cases reported showing that BML can occur even without a history of gynecologic surgery [2]. Another theory relates to in situ hormone-sensitive proliferation of smooth muscle cells [4]. Karyotypic and molecular studies indicate that BML is clonally derived from benign-appearing uterine leiomyomas [5].
BML may show a range of clinical symptoms depending on the location of involvement and the number and size of the tumors. Although a detailed medical history and imaging studies are helpful in diagnosis, definitive diagnosis is dependent on pathologic examination. In pathologic evaluation, benign-appearing spindle-shaped cells reveal that the tumor is of a smooth muscle nature. Positive immunohistochemical staining for desmin, vimentin, SMA, ER, PR, negative for S-100 antigen, and a Ki-67 index less than 1%, signifying a low proliferate rate, confirm that benign mesenchymal tumors are similar to leiomyomas of uterine origin. Histopathologic features with low mitotic index (less than 5 mitoses per high-power field [hpf]), lack of nuclear atypia, absence of coagulative necrosis, and minimal vascularization differentiate the tumor from leiomyosarcoma [4].
In their review of 161 patients with BML, Barnas et al. reported that 128 of the patients had only lung metastases, and nine patients had lung and concomitant metastases. In 47.5% of the cases, the diagnosis was made when the patient was symptomatic, and the rest were found incidentally. The mean age at the first surgery was 38.5 years, the mean age at diagnosis was 47.3 years, and the average interval between the first surgery and diagnosis was 8.8 years [2]. Previously published data speculate that the estimated time from initial surgery to diagnosis of BML is 10 to 15 years [6]. Our case differs from other cases in the literature because it was diagnosed at the age of 30 years, only 1 year after the initial surgery, with a large size metastasis concurrent with lung metastasis.
Being positive for ER, frequently found in premenopausal patients, regression of lesions in cases of menopause and termination of pregnancy when endogenous estrogen decreases or when medical/surgical castration is performed, indicates that estrogen is the main factor in lesion progression [7].
Although there is no consensus on treatment, treatments aimed at reducing estrogen have been used in line with these findings. Close follow-up in young and asymptomatic patients, surgical removal of the metastatic tumor, medical treatment for suppressing endogenous estrogen in cases where surgery is not possible or not preferred have been suggested and performed for treatment. Medical castration with hormonal therapy such as GnRHa, progesterone antagonists (mifepristone), selective estrogen receptor modulators (SERMs), estrogen receptor antagonists (tamoxifen), or aromatase inhibitors (letrozole) could be recommended [1,7]. However, interestingly, it has been shown that lesions in postmenopausal patients may be resistant to hormonal therapy and may even progress [7]. There may be some other biologic controls or hormonal factors in the behavior of BML.
Nucci et al. [8] suggested that BML might originate from a biologically distinctive subset of uterine fibroids, in which chromosomal aberrations (19q and 22q terminal deletions) have been identified, found in approximately 3% of patients who have uterine leiomyoma. This result may help explain why every patient with leiomyoma does not develop BML. However, BML, which is a rare and complex condition, still has many unknowns. The overall incidence of BML after leiomyoma is unknown. The origin of individual differences in the response rate to medical treatment and progression pattern is unknown.
Conclusion
Our case, in which we are concerned that the increased oestrogen during pregnancy might continue to severely progress the existing myomas in the uterus and metastatic lesions, is important because it shows that this disease, which is stated to be effectively treated with surgical or medical castration, may still allow for a term pregnancy. Especially in young patients, after excluding the possibility of primary or concurrent malignancy of the tumor, untreated follow-up and determining the individual progression behavior of BML may be an appropriate approach.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Pacheco-Rodriguez G, Taveira-DaSilva AM, Moss J. Benign metastasizing leiomyoma. Clin Chest Med. 2016;37(3):589–95
2. Barnas E, Ksiazek M, Ras R, Skret A, Skret-Magierlo J, Dmoch-Gajzlerska E. Benign metastasizing leiomyoma: a review of current literature in respect to the time and type of previous gynecological surgery. PLoS One. 2017;12(4): e0175875
3. Aoki K, Yamamoto T, Terauchi R, Mori T, Shirai T, Kitawaki J. Benign metastasizing leiomyoma in femur and thigh with a history of uterine leiomyoma: A case report and literature review. J Obstet Gynaecol Res. 2021; 47(2):812-7.
4. Awonuga AO, Shavell VI, Imudia AN, Rotas M, Diamond MP, Puscheck EE. Pathogenesis of benign metastasizing leiomyoma: a review. Obstet Gynecol Surv. 2010; 65(3):189-95.
5. Bowen JM, Cates JM, Kash S, Itani D, Gonzalez A, Huang D, et al. Genomic imbalances in benign metastasizing leiomyoma: characterization by conventional karyotypic, fluorescence in situ hybridization, and whole genome SNP array analysis. Cancer Genet. 2012; 205(5):245-54.
6. Wei WT, Chen PC. Benign metastasizing leiomyoma of the lung: A case report and literature review. Oncol Lett. 2015; 10(1):307-12.
7. Fan R, Feng F, Yang H, Xu K, Li S, You Y,et al. Pulmonary benign metastasizing leiomyomas: a case series of 23 patients at a single facility. BMC Pulm Med. 2020; 20(1):292.
8. Nucci MR, Drapkin R, Dal Cin P, Fletcher CD, Fletcher JA. Distinctive cytogenetic profile in benign metastasizing leiomyoma: Pathogenetic implications. Am J Surg Pathol. 2007; 31: 737–43.
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Fatma Nurgül Taşgöz, Melih Çekinmez. Term pregnancy after the diagnosis of benign metastasizing leiomyomatosis. Ann Clin Anal Med 2022;13(Suppl. 2):S130-133
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Emergency resection of obstructing thyroid lymphoma causing stridor: A case report
Arsalan Siraj 1, Taha Naveed 2, Shah Bano 2, Moazama Afzal 2, Afia Shafiq 3, Aslam Khan 4
1 Department of Surgery, 2 Final Year Medical Student, 3 Department of Pathology, 4 Department of Otorhinolaryngology, HITEC Institute of Medical Sciences, Taxila Cantt, Pakistan
DOI: 10.4328/ACAM.21153 Received: 2022-03-20 Accepted: 2022-06-17 Published Online: 2022-09-03 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S134-137
Corresponding Author: Taha Naveed, HITEC Institute of Medical Sciences, 47070, Taxila Cantt, Pakistan. E-mail: taha.naveed8526@gmail.com P: +92 333 196 23 06 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2814-2652
Primary thyroid lymphoma is a relatively rare histological entity, accounting for about 2% of extra-nodal lymphomas and only 0.5-5% of all thyroid malignancies. The incidence rate is just two per million individuals, best treatment options and critical prognostic variables have yet to be determined. Herein, we report the case of a 48-year-old woman who presented with acute stridor and life-threatening airway obstruction, due to a rapidly expanding thyroid lymphoma, which required emergency intervention. Our patient was submitted to a total thyroidectomy based on her symptoms since we did not have a definitive diagnosis at the time, Fine Needle Aspiration Cytology (FNAC) was only suggestive of a lymphoproliferative disorder. Six sessions of rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, and prednisone (R-CHOP) were indicated after a post-operative histopathology report confirmed the diagnosis of diffuse large B-cell lymphoma, which resulted in complete disease remission. This report indicates that even though chemo-radiation is considered the gold standard for the treatment of lymphomas, the existence of obstructive symptoms warrants thyroidectomy, as was done in this case.
Keywords: Thyroidectomy, Lymphoma, Stridor, Emergency
Introduction
A thyroid enlargement, causing acute respiratory failure, due to thyroid compression or invasion of the tracheal lumen, presents as a rare clinical emergency warranting urgent surgical intervention. Thus, in these exceptional cases, total thyroidectomy, which is otherwise a routine elective operation, has to be resorted to on an emergency basis for life-threatening airway obstruction [1].
This airway compression may be caused by giant goiters (especially if extending substernal), acute intra-thyroidal hemorrhage, and thyroid malignancies (mostly due to anaplastic carcinoma, secondaries, and as in this case, a primary thyroid lymphoma) [1]. Dyspnea may also become critical in the latter group due to bilateral recurrent laryngeal nerve involvement and result in vocal cord palsy with stridor [1]. Massive bleeding severe enough to cause acute airway distress is rare and usually occurs as a result of neck trauma rather than as a result of thyroid illness [1]. The purpose of this paper is to describe one such patient who was successfully treated with total thyroidectomy in the emergency room due to ingravescent dyspnea and hypoxia, as well as to examine related data from the literature.
Case Report
A 48-year-old female presented to the outpatient department (ENT) of HIT hospital, Taxila Cantt with acute stridor and labored breathing, suffered acute respiratory failure and passed out in the waiting area. The episode could have been fatal if not for the intervention. The patient was immediately shifted to the operation theatre. Emergency intubation was done, followed by total thyroidectomy. Tracheostomy was also performed later on once there was no hindrance by the thyroid mass.
A brief history: Eight months before her surgery, in February 2021, the patient experienced pain in the neck associated with diffuse swelling, which was hardly noticeable at that time. As per instructions of a general practitioner, the patient was recommended thyroid function tests. A diagnosis of hypothyroidism was made and thyroxine was prescribed. To the patient’s dismay, there was no improvement in pain; instead, she developed breathing difficulties, which intensified with time. In the first week of October 2021, there was an unanticipated increase in the size of the swelling, and within two weeks it presented with limited neck extension, and severely restricted neck flexion. Meanwhile, orthopnea was also initiated, which was relieved with semi-recumbent positioning to help her sleep. Just four days from surgery, the patient presented with extreme dyspnea and a salbutamol inhaler was advised, which was not complied with. A fine needle aspiration was performed with results of no diagnostic relevance reported. The dyspnea worsened and she presented to the Heavy Industries Taxila Hospital on 27th October 2021.
Management procedure: On laryngoscopy, the laryngeal opening was compressed by the thyroid mass and was deviated to the left. Emergency intubation was done with a Rapid Sequence Induction Technique (RSII); a reinforced endotracheal tube was passed and checked for bilateral air entry. The surgical team opted for an endotracheal intubation. The intubation though riddled with complications was achieved without any major complications.
The initial surgical plan indicated an isthmectomy, which was later replaced by a total thyroidectomy when the surgical exploration revealed a large thyroid tumor involving both the lobes and extending down to the retrosternal and parapharyngeal spaces. There was bilateral involvement of lymph nodes, at the levels IIA, III, IV and V. 420 grams of thyroid tissue were removed and a tracheostomy was performed to relieve breathing. Unfortunately, intraoperatively left recurrent laryngeal nerve was damaged, which resulted in the development of hoarseness of voice. The patient underwent 6 cycles of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone).
Histopathological findings suggested classical features of Non-Hodgkin’s lymphoma. This was a primary lymphoma of the thyroid gland, though lymphomas in this anatomical sector can be of extra-thyroid origin too. Vesicular nuclei, showing a high nucleocytoplasmic ratio (Figure 2C- red) with enhanced hematoxylin staining were conclusive of neoplasia. Apparent mitotic figures (figure 2D- blue), indicative of enhanced cell division also suggested similar findings regarding neoplasia. Histopathological analysis indicated a diffuse Large B-cell lymphoma, Post Germinal type, with strong positive expression of CD 20 and MUM 1, it was also weakly positive for BCL 2. There was a negative expression of TTF 1, PAX 8, CD 3, CD 10, BCL 6 and C-MYC.
Discussion
Despite the fact that Hedenus [1] recorded thyroidectomy for “suffocating” goitres in 1821, airway obstruction due to goitre is now uncommonly mentioned in the literature due to improved diagnostic methods and earlier treatment. Although this spectacular occurrence appears to be more common in underdeveloped countries due to ignorance and lack of inexpensive medical treatments, the phenomenon of enormous goitres is rarely reported in Western countries as well [1]. However, since the tracheal lumen can be gradually constricted without presenting symptoms up to 75% of the cases, truly severe life-threatening airway obstruction is now an exceptionally unusual occurrence [1].
Spontaneous intrathyroidal hemorrhage, invasion of the tracheal lumen by primitive or secondary tumors, severe compression from benign or malignant masses, and bilateral vocal cord palsy resulting from infiltration of recurrent nerves from thyroid malignancy are the four etiopathogeneses of severe respiratory distress in non-traumatic thyroid disease [1].
Our patient is known to have hypothyroidism as per history, which coincides with Hashimoto’s thyroiditis. Hashimoto is a potentially benign condition but it is the cause of many malignancies, especially lymphomas derived from MALT. In individuals who arrive with an increasing neck mass and a history of Hashimoto’s thyroiditis, it is imperative to rule out primary thyroid lymphoma since Hashimoto’s is the most significant risk factor for PTL [2], implying that Hashimoto’s disease is part of an immunological response that elicits primary thyroid lymphoma. Regardless of the underlying pathology, it is strongly indicated that prompt treatment must ensue once goiter is associated with features of airway compression, including dyspnea, orthopnea and stridor. Once significant respiratory compromise sets in, it is recommended to hospitalize such patients aimed at close observation, prompt workup and the need for imminent intervention. The size of a goitre is a poor predictor of upper airway obstruction when measured. Consequently, CT scanning has become the gold standard for deciding the extent of retrosternal goitre and its relationship to neighboring structures, and it can be used to identify patients who might need a thoracic intervention [3]. It is noteworthy that asymptomatic multinodular goiter can unpredictably result in airway obstruction, regardless of the duration, volume, or intrathoracic extension of the goiter. In these patients with upper airway compression, obstructive findings on pulmonary function test also do not relate with tracheal reduction on CT scans. Recognition of these cases is imperative, as they constitute a preventable cause of mortality if timely diagnosed and treated. Thyroid lymphomas, the cause of airway compromise in our case, represent a small but significant subset of such patients. Primary thyroid lymphomas represent 5% of thyroid malignancies and 2% of extra-nodal lymphomas typically present as progressively enlarging goiters, sometimes in the backdrop of Hashimoto’s thyroiditis, which may present as diagnostic difficulty because of the mostly nonspecific sonographic features and low diagnostic yield of FNAC in the absence of Immunophenotypic analysis. Diffuse Large B-cell lymphomas and more indolent MALT lymphomas variety comprise the most common primary thyroid lymphomas.
In terms of the histopathology, diffuse Large B-Cell Lymphoma (DLBCL) is classified into two types as follows: 1) Germinal Center DLBCL and 2) Post-Germinal Center DLBCL/Activated B-cell like lymphoma. CD10, BCL6 and MUM-1 immunohistochemistry markers are directive for diffuse large B-Cell lymphoma (DLBCL). According to the Hans Algorithm [4], to approximate molecular subtypes based on Immunohistochemical patterns; positive findings of CD10 or BCl6 are conclusive of the Germinal Centre (GC) type. If MUM-1 is positive then it is classified as Post-Germinal Centre (Post-GC). Positive expression of CD20 is specific for a B cell Lymphoma because it is the baseline immunofluorescence marker for B cells. GC DLBCL has a better prognosis than the Post GC DLBCL with CHOP therapy with an overall survival of 60% [5]. When activated B cell DLBCL is treated with normal chemoimmunotherapy, the outcomes are significantly worse. [6]. Immunostaining, like cDNA microarrays, can be used to distinguish between GCB and non-GCB subtypes of DLBCL and predict their survival.
Radiotherapy for local disease, and Combined Modality with chemotherapy, typically involving R-CHOP (Rituximab, Cyclophosphamide, Vincristine, Doxorubicin and Prednisolone) form the mainstay of treatment of stage IIIE and IV PTL. Chemotherapy with or without radiation is the indicated treatment option. These noninvasive methods offer a considerable mortality benefit over surgical resection, which is generally not recommended as first-line therapy [7].
Establishing a secure airway and induction of general anesthesia presents the first challenge when the patient in such a dramatic event presents to the emergency or operation suite. Awake fiberoptic intubation using a small endotracheal tube followed by induction of general anesthesia may offer a quick and safer approach compared to a standard sequence of induction and intubation but the later approach may be preferred in unsafe patient. On the other hand, an inhalation induction followed by laryngoscopy and orotracheal or blind nasal intubations, may be considered dangerous because of the complete airway obstruction following loss of consciousness [1].
The second step is the choice of surgical treatment to be performed. Indeed, emergency surgery is always indicated for severe airway obstruction caused by a thyroid mass [1]. In the presence of thyroid mass, an emergency tracheostomy is hindered, while an isthmectomy to allow a tracheostomy appears to be an incomplete treatment. Total, near-total or sub-total thyroidectomy represents the treatment of choice of acute airway obstruction resulting from compression of thyroid mass. Lastly, after establishing a definitive airway via endotracheal intubation, the role of tracheostomy at the end of the procedure is questionable, as a total thyroidectomy is capable of resolving airway obstruction, thus tracheostomy may be deemed unnecessary. However, it can still be justified to perform tracheostomy if there is marked tracheomalacia [1]. There is a higher risk of postoperative hypoparathyroidism, vocal cord palsy and hemorrhage reported for thyroidectomies performed for acute airway obstruction and retrosternal goiters. Continuous intraoperative nerve monitoring is a safe and effective way to minimize Recurrent laryngeal nerve paralysis in thyroid surgery. [8].
Conclusion
In conclusion, on the basis of our experience and of the literature review, we strongly advocate elective surgery for patients with thyroid disease at the first signs of tracheal compression as the first modality of intervention in obstructing thyroid lymphomas; once a patent airway is maintained, chemotherapy can follow later on the treatment timeline. When acute airway distress appears, an emergency life-threatening total thyroidectomy is recommended in a high-volume center.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Testini M, Logoluso F, Lissidini G, Gurrado A, Campobasso G, Cortese R, et al. Emergency total thyroidectomy due to non-traumatic disease. Experience of a surgical unit and literature review. World J Emerg Surg. 2012; 7(1):1-9.
2. Travaglino A, Pace M, Varricchio S, Insabato L, Giordano C, Picardi M, et al. Hashimoto thyroiditis in primary thyroid non-Hodgkin lymphoma: a systematic review and meta-analysis. Am J Clin Pathol. 2020;153(2):156-64.
3. Dias T, Santos A, Mesquita C, Santos RM. Acute airway obstruction due to benign multinodular goitre. BMJ Case Rep. 2019;12(4):e228095.
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5. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937-47.
6. Nowakowski G S, Czuczman M S. ABC, GCB, and double-hit diffuse large B-cell lymphoma: does subtype make a difference in therapy selection. Am Soc Clin Oncol Educ Book. 2015; 35(1):e449-e457.
7. Noble VV, Ermann DA, Griffin EK, Silberstein PT. Primary thyroid lymphoma: an analysis of the national cancer database. Cureus. 2019; 18:11(2). DOI: 10.7759/cureus.4088.
8. Ku D, Hui M, Cheung P, Chow O, Smith M, Riffat F, et al. Meta-analysis on continuous nerve monitoring in thyroidectomies. Head Neck. 2021; 43(12):3966-78.
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Arsalan Siraj, Taha Naveed, Shah Bano, Moazama Afzal, Aslam Khan, Afia Shafiq. Emergency resection of obstructing thyroid lymphoma causing stridor: A case report. Ann Clin Anal Med 2022;13(Suppl. 2):S134-137
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Bladder hemangiomas: A rare cause of persistent gross hematuria in children
Veysel Kaplanoğlu 1, Hatice Kaplanoğlu 2, Emin Taha Keskin 3
1 Department of Radiology, Health Sciences University, Ankara Ataturk Sanatory Educatıon and Research Hospıtal, Ankara, 2 Department of Radiology, Health Sciences University, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, 3 Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21161 Received: 2022-03-23 Accepted: 2022-06-06 Published Online: 2022-06-08 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S138-140
Corresponding Author: Veysel Kaplanoğlu, Department of Radiology, Health Sciences University, Keçiören Training and Research Hospital, Ankara, Turkey. E-mail: hatice.altnkaynak@yahoo.com.tr P: +90 0505 892 30 61 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1376-0469
Hemangiomas are benign vascular tumors that can occur almost anywhere in the human body. A bladder hemangioma is rare, constituting only 0.6% of all bladder tumors. It is less common in childhood and adolescence. Its treatment is controversial due to the risk of bleeding. An 11-year-old male patient presented with persistent gross hematuria and pelvic pain. Cystoscopy revealed fibrotic bands in the bladder and hemangioma areas that were raised from the mucosa and not raised from the surface at the junction of the left lateral wall of the bladder dome and on the left side of the bladder neck. Endovascular embolization was performed with polyvinyl alcohol particles. During follow-up in the last year, no local recurrence was observed, and there was no hematuria according to the urinalysis. It is very important to distinguish bladder hemangiomas from other malignant vascular tumors since the required treatment approach and prognosis significantly differ.
Keywords: Bladder Hemangioma, Children, Ultrasonography, CT, MRI
Introduction
Hemangiomas are benign vascular tumors. They can be seen everywhere in the human body and are mostly localized in the skin and subcutaneous soft tissues.
Infection, trauma, metabolic diseases, autoimmune diseases and glomerulonephropathies are the main causes of gross hematuria in children [1]. Neoplasms in the urinary system in children are not common due to the lower incidence of epithelial tumors [1]. Bladder hemangiomas (BH) are rarely reported [1]. In this case report, we defined multiple BH as a rare cause of pediatric persistent gross hematuria and presented imaging findings.
Case Report
A four-year-old boy was diagnosed with BH in an external center based on the presence of gross hematuria with clots, and a partial cystectomy was performed. The patient was not followed up. When he was 11 years, he presented to the pediatrics and urology clinic of our hospital with persistent gross hematuria and pain in the pelvic region. In urinary ultrasonography, numerous heterogeneous hyperechoic lesions were detected, which impacted the bladder wall (BW) and protruded toward the lumen. The largest of these lesions was approximately 37×20 mm and located on the left lateral wall in the anterior inferior section. On color Doppler (superb microvascular imaging), these lesions were observed as a mass with minimal blood flow, containing anechoic vascular areas in the center (Figure 1).
Computed tomography revealed heterogeneous hyperdense lesions protruding from the BW to the lumen and containing irregularly shaped hypodense areas (Figure 2).
Magnetic resonance imaging (MRI) showed lobule-contoured heterogeneous hyperintense lesions protruding from the BW to the lumen, prominent in the anterior left lateral wall and trigone, containing hypointense areas on T1-weighted and T2-weighted images, occasionally showing minimal diffusion restriction, and demonstrating heterogeneous contrast enhancement after contrast agent injection with a gradual increase in enhancement (Figure 3).
In cystoscopy, fibrotic bands were observed in the bladder, and there were hemangioma areas that are raised at the mucosa and not raised at the surface at the junction of the bladder left lateral wall dome and the bladder neck on the left side. The patient underwent endovascular embolization with PVA particles. In the postoperative pelvic US examination, it was observed that intraluminal lesions located in the bladder lumen had decreased in size. The patient was followed up with repeated cystoscopy and abdominal CT at six-month intervals. No local recurrence was observed in the last-year follow-up, and there was no hematuria in the urinalysis. Informed consent was obtained from the patient’s relative.
Discussion
BH are benign congenital malformations of vascular structures. Non-urothelial neoplasms are clinically extremely rare and constitute only 0.6% of all bladder tumors [2]. BH can be seen in all age groups, it is less common in children and adolescents. It is most common under 30 years of age [2]. Most BH are solitary (66%), most commonly seen in the dome, posterior wall, and bladder trigon. Since its diameter ranges from a few millimeters to 10 cm, it increases the diagnostic difficulties of the intramural tumors of the bladder [2].
The most common clinical symptom of a BH is painless recurrent isolated gross macroscopic hematuria and less commonly suprapubic pain due to vesical irritation and urinary retention. However, in cases with massive bleeding, hypovolemic shock may occur [2, 3]. Ureteral obstruction by the mass can cause hydroureteronephrosis, and in the presence of massive bleeding, the hematoma may hide the mass in the bladder [2].
Most cases reported that BH (3-6%) may be associated with cutaneous hemangioma or Klippel-Trènaunay-Weber syndrome [4]. A bladder hemangioma may also be associated with Sturge-Weber syndrome or encephalo-trigeminal-angiomatosis, Osler-Weber-Rendu disease, hemorrhagic telangiectasia syndrome, and systemic angiomatosis [2, 4]. In addition, 30% of BH are accompanied by hemangiomas in other parts of the body [1]; therefore systemic evaluation is strongly recommended in these patients [4]. In the current case, no other accompanying hemangioma was observed in the body. Of the three characterized histological subtypes of hemangioma, the cavernous form is the most common, followed by capillary and arteriovenous subtypes [1].
Differential diagnosis of children with painless gross hematuria with a polypoid bladder mass includes hemangioma, rhabdomyosarcoma (RMS), other vascular tumors, inflammatory pseudotumor, leiomyoma, neurofibromatosis, pheochromocytoma, transitional cell papilloma, transitional cell carcinoma, and pseudotumoral cystitis. The most common tumor originating from the bladder is RMS, and it is observed as a polypoid mass. Other vascular tumors of the bladder can also cause hematuria, but are rare in children [5]. The inflammatory pseudotumor of the bladder usually presents as a polypoid mass or a submucosal nodule with ulceration and bleeding [6].
Treatment options for bladder hemangiomas vary from one individual to another with appropriate follow-up. The size, localization and depth of the mass are important in the treatment of BH, and its treatment is controversial [7]. For small lesions (≤3 cm) and asymptomatic hemangiomas, follow-up is s recommended. Surgical treatment should be considered in life-threatening conditions such as severe abdominal pain, severe hematuria causing anemia, and suspected malignancy [7]. Treatment options are follow-up, transurethral resection, electrocoagulation, radiation, systemic steroid administration, endovascular embolization, sclerosing agent injection, interferon-a-2 therapy, YAG-laser therapy, and partial or radical cystectomy [8]. Transurethral endoscopic surgical resection is the gold standard in the diagnosis and treatment of small BH. Follow-up is mandatory to detect recurrence or residual tissue after treatment [7].
Conclusion: Bladder hemangiomas are benign, non-urothelial tumors that are rarely seen in pediatric and adolescent patients. There is no pathognomonic finding in clinical presentation, but painless gross hematuria is the most common complaint. It is very important to distinguish bladder hemangiomas from other malignant vascular tumors since the required treatment approach and prognosis significantly differ. Treatment options vary on a case basis and are individualized. Pre-treatment follow-up is necessary for small and asymptomatic lesions, and post-treatment follow-up is mandatory for the detection of recurrence or residual disease.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Kim YY, Kim MJ, Lee MJ, Kim JY. Multiple hemangiomas of the urinary bladder in a child with gross hematuria. Ultrasonography. 2015;34 (3):231-4.
2. Zhao GC, Ke CX. Haemangiomas in the urinary bladder: Two case reports. World J Clin Cases. 2021;9 (16):3927-35.
3. Saribacak A, Ozkurkcugil C, Ozkan L. Arteriovenous hemangioma of the urinary bladder following intra vesical treatment. Urol J. 2011;8(3):251-3.
4. Favorito LA. Vesical hemangioma in patient with Klippel-Trenaunay-Weber Syndrome. Int Braz J Urol. 2003;29 (2):149-50.
5. Geramizadeh B, Banani A, Foroutan H, Aminsharifi A, Karimi M. Malignant epithelioid hemangioendothelioma of the bladder: the first case report in a child. J Pediatr Surg 2009;44(7):1443-45.
6. Asanuma H, Nakai H, Shishido S, Tajima E, Kawamura T, Morikawa Y, et al. Inflammatory pseudotumor of the bladder in neonates. Int J Urol. 2000;7(11):421-4.
7. Jibhkate S, Sanklecha V, Valand A. Urinary bladder hemangioma -a rare urinary bladder tumor in a child. APSP J Case Rep. 2015;6(1):6.
8. Syu SH, Chan KS, Hsiao CH, Chen WY, Lee LM, Wen YC. A Large Urinary Bladder Hemangioma Mimicking Urachal Cancer: A Case Report and Literature Review. Urology. 2019;123:224–6.
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Veysel Kaplanoğlu, Hatice Kaplanoğlu, Emin Taha Keskin. Bladder hemangiomas: A rare cause of persistent gross hematuria in children. Ann Clin Anal Med 2022;13(Suppl. 2):S138-140
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Aseptic meningitis caused by Coronavirus OC43 in a child: A case report
Yasemin Demirbaş 1, Ayşegul Alpcan 1, Mikail İnal 2, Şeyma Guney 1, Serkan Tursun 1,Yaşar Kandur 1
1 Department of Pediatrics, 2 Department of Radiology, School of Medicine, Kirikkale University, Kirikkale, Turkey
DOI: 10.4328/ACAM.21192 Received: 2022-04-15 Accepted: 2022-06-10 Published Online: 2022-06-18 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S141-143
Corresponding Author: Aysegul Alpcan, Department of Pediatrics, Kırıkkale University, Kırıkkale, Turkey. E-mail: ozcalk@yahoo.com P: +90 318 357 42 42 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9447-4263
Human coronavirus OC43 (HCoV-OC43) is one of the coronaviruses that cause the mild cold. On the other hand, extra-respiratory manifestations such as central nervous system infections with HCoV-OC43 are very rarely reported. We present a case of a previously healthy immunocompetent child with acute aseptic meningitis, as a result of HCoV-OC43 who admitted to the emergency department with a complaint of unconsciousness.. Respiratory tract and cerebrospinal fluid culture showed HCoV-OC43 in viral screening. During the follow-up period, the patient was completely asymptomatic, with normalized consciousness. The clinicians should keep in mind that HCoV-OC43 can be the etiological agent in the differential diagnosis of aseptic meningitis in immunocompetent individuals with reversible neurological symptoms.
Keywords: Aseptic Meningitis, Cerebrospinal Fluid, Children, Human Coronavirus, HCoV-OC43
Introduction
Central nervous system (CNS) infections are categorized as meningitis and encephalitis [1]. Aseptic meningitis, with negative bacterial and fungal cultures is the most common form of meningitis. Acute onset of meningeal irritation signs and cerebrospinal fluid (CSF) pleocytosis; (CSF) under microscopy (40x) shows more than 5 white blood cells/mm3) [2]. The viral etiology of the majority of aseptic meningitis cases is unknown. However, the development in PCR technology provided us to diagnose viral microorganisms [3]. Human coronaviruses (HCoVs) OC43 are associated most frequently with upper respiratory tract infection and less frequently with lower respiratory tract infections, including bronchiolitis, croup, and pneumonia, primarily in infants and especially in immunocompromised children. On the other way, extra-respiratory manifestations such as CNS infections with HCoV-OC43 have been reported very rarely. Herein we report a case of a previously healthy immunocompetent 2-year-old male with acute aseptic meningitis, as a result of HCoV-OC43
Case Report
A 2-year-old male presented unconsciousness with no exacerbating or relieving factors. There were no additional complaints suggesting infection such as fever, runny nose, cough, malaise, diarrhea, and vomiting. His brother had been coughing for 4 days who was also autistic. His weight was 11 kg (3-10 percentile). His blood pressure was 90/60 mm Hg. He had a heart rate of 100 beats/min, body temperature of less than 36.5°C, and SpO2 of 98% on room air. No skin rash was reported. He had a tendency to sleep and was restless. His pediatric coma scale was 9. The rest of his full neurological assessment was within normal limits. During the follow up period neck stiffness and a positive Kernig’s sign was elicited in two hours. He had normal papillary reflexes and no sign of bilateral papilledema. His body temperature became 37.8°C. His blood tests revealed normal renal, liver biochemistry and venous blood gas analysis. The full blood count revealed a white blood cell count of 6240 µL (neutrophils: 49%, lymphocytes: 44%, monocytes 5%, eosinophils 2%), hemoglobin 10.2 g/dL and thrombocyte count of 429.000/mm3. The CRP was 6.08 mg/L (N<5). Lumbar puncture (LP) was made for clinical diagnosis of meningitis. No microorganisms were isolated in (CSF). His contrast-enhanced computed tomography showed mild enlargement of the extracerebral CSF space in the bilateral frontal area (Figure 1). The CSF examination showed no white cell count, but 10 erythrocytes /mm3. The CSF glucose level was 50 mg/dl (simultaneous blood glucose was 74 mg/dl) and the protein level was 15 mg/dl. Herpes PCR, Herpes type 1-2 IgM, Herpes type 1-2 IgG serologies sent from the CSF were negative. CSF culture for bacteria was also negative. Due to the COVID-19 pandemic, we searched also COVID-19 PCR, which was negative. Interestingly respiratory viral screening showed HCoV-OC43. Therefore, CSF was also searched for HCoV-OC43 PCR that was found positive. The quantitative immunoglobulin levels (Ig G, M, A) were in the normal range. During the follow-up period the patient was recovered, with normalized consciousness.
Discussion
This was a case of aseptic meningitis due to HCoV-OC43 in a healthy child with central nervous system symptoms. According to our knowledge, there are very rare reports of meningitis secondary to HCoV-OC43 among immunocompetent pediatric patients.
Meningitis is an acute inflammation of the meninges. The presenting symptoms of meningitis are headache, fever, vomiting, neck stiffness and sometimes consciousness [4]. The diagnostic tests currently used to detect viral microorganisms that cause CNS infections are multiplex PCR assay and metagenomic next-generation sequencing (mNGS) [5]. Thus, we detected HCoV-OC43 using multiplex PCR assay. The unknown causes were probably due to the limitations of laboratory testing, such as the limitation of PCR panel testing. Meningitis of unknown cause was reported in 81.5% in the USA, and 42% in the UK [6].
Following the SARS global outbreak, some clinical laboratories started offering comprehensive respiratory molecular diagnostic testing using reverse transcriptase-polymerase chain reaction (RT-PCR) assays, some of which include HCoVs 229E, OC43, NL54, and HKU1 as targets. Thus, we diagnosed the microorganism, otherwise it could have been skipped.
Coronaviridae are the largest enveloped RNA viruses with a positive single-stranded RNA molecule [7]. HCoV-OC43 belongs to the Betacoronavirus genus like SARS-CoV-2 [8]. Multiplex PCR for CSF was positive for HCoV-OC43, which led to the final diagnosis. It was considered reasonable to assume that the infection had been caused by HCoV-OC43 after the detection in the nasopharyngeal swab fluid.
Conclusion
This case demonstrates that HCoVs-OC43 may be considered in differential diagnosis of aseptic meningitis in immune-competent individuals with reversible neu¬rological symptoms.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. WrightWF, Pinto CN, Palisoc K, Baghli S. Viral (aseptic) meningitis: Areview. J Neurol Sci. 2019; 398:176–83.
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Yasemin Demirbaş, Ayşegul Alpcan, Mikail İnal, Şeyma Guney, Serkan Tursun1,Yaşar Kandur. Aseptic meningitis caused by Coronavirus OC43 in a child: A case report. Ann Clin Anal Med 2022;13(Suppl. 2):S141-143
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Pulmonary thromboembolism and thrombolytic treatment in total knee arthroplasty: A case report
Alikemal Yazıcı 1, 2, Ümit Aygün 3, 4
1 Department of Orthopaedics and Traumatology, Faculty of Medicine, Near East University, Nicosia, Cyprus, 2 Department of Orthopedics and Traumatology, Buyuk Anadolu Hospital, Samsun, Turkey, 3 Department of Orthopaedics and Traumatology, Faculty of Medicine, Istinye University, VM Medical Park Samsun Hospital, Istanbul, Turkey, 4 Department of Orthopaedics and Traumatology, Faculty of Medicine, VM Medical Park Samsun Hospital, Samsun, Turkey
DOI: 10.4328/ACAM.21251 Received: 2022-05-29 Accepted: 2022-06-29 Published Online: 2022-08-29 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S144-147
Corresponding Author: Ümit Aygün, Department of Orthopaedics and Traumatology, Faculty of Medicine, Istinye University, Istanbul, Turkey. E-mail: aygun.umit@yahoo.com P: +90 505 558 13 21 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7234-1654
Pulmonary thromboembolism (PTE) is a fatal complication of total knee arthroplasty (TKA). Thrombolytic treatment is of critical importance in PTE treatment. In patients not administered thromboprophylaxis in TKA operations, deep vein thrombosis (DVT) has been reported at the rate of 50-70%, PTE at 5%, and fatal PTE at 1-4%. In this study, we present a case who developed PTE after TKA surgery. Thrombolytic therapy, which is an absolute contraindication in the treatment of massive PTE after major orthopedic surgery, can become a relative contraindication in life-threatening situations, and early diagnosis and treatment in a short time can be life-saving without causing major bleeding.
Keywords: Pulmonary Thromboembolism, Thrombolytic Treatment, Total Knee Arthroplasty, Ultrasonography, Echocardiography
Introduction
PTE is the condition forming as a result of a thrombus blocking the pulmonary artery and branches, which usually forms in the deep veins of the lower extremities and occasionally in other veins throughout the body (upper extremities, abdomen). PTE can occur in three forms; first as a non-massive form with normal systemic blood pressure and right ventricle functions, second as a submassive form in which blood pressure is normal but right ventricular dysfunction findings (right ventricular dilatation, moderate and severe hypoxia, paradoxical movement in the septal wall and deviation to the left) on echocardiography, and third as a massive form, which is the most severe with hypotension, right ventricle dysfunction, shock, and cardiopulmonary arrest (Arseven O, Bingöl Z, Çöplü L, Erol S, Oğuzülgen İK, Okumuş NG, et al. Arseven O, editor. Pulmoner Tromboembolizm Tanı ve Tedavi Uzlaşı Raporu/ Pulmonary Thromboembolism Diagnosis and Treatment Consensus Report. Türk Toraks Derneği/ Turkish Thoracic Society. 2021. p. 1-124). In patients not administered thromboprophylaxis in TKA operations, deep vein thrombosis (DVT) has been reported at the rate of 50-70%, PTE at 5%, and fatal PTE at 1-4%. In patients applied with DVT prophylaxis, DVT has been reported at the rate of 0.9-5%, PTE at 0.27-1.1%, and fatal PTE at 0.1-0.5%. The risk of PTE is significantly higher following simultaneous bilateral TKA than following single unilateral TKA [2-4].
There are several risk factors causing PTE, the most important of which are major orthopaedic surgical interventions. Dyspnea, tachypnea, tachycardia, persistent hypotension (systolic blood pressure ≤90 mmHg or arterial blood pressure ≥40mmHg compared to the basal value within 15 mins under observation), pleuritic lateral chest pain, cough, hemoptysis, cyanosis, anxiety, a feeling of substernal pressure, mental confusion, and syncope may be seen in PTE cases. It has been stated that ≥50% of the pulmonary vessel bed is obstructed in massive PTE [1]. The most important step in diagnosis is suspicion of PTE. Patients with suspected PTE must be rapidly evaluated and for diagnosis, examinations must be made first of D-dimer, lower extremity compression ultrasonography, echocardiography, and multidetector computed tomography (CT) angiography .
In the treatment of PTE, general supportive treatment is applied together with anticoagulant treatment, thrombolytic treatment, embolectomy performed with surgery and percutaneous catheter techniques, and vena cava inferior filter [2, 3]. Thrombolytic drugs, which provide active dissolution of the thrombus by converting plasminogen to plasmin, are the drugs first administered in PTE treatment. Currently, the most commonly used thrombolytic drugs are recombinant human tissue-type plasminogen activator (alteplase), streptokinase, and urokinase. The main indication for thrombolytic treatment is massive PTE in which persistent hypotension develops without another associated cause such as newly emerging arrhythmia, hypovolemia, and cardiogenic shock, and/or sepsis. It has been stated that when thrombolytic treatment is administered within 48 hours, it is more effective [2].
Our aim in presenting this case is to show that thrombolytic therapy, which is an absolute contraindication in the treatment of massive PTE after major orthopedic surgery, can become a relative contraindication in life-threatening situations, and that early diagnosis and treatment in a short time can be life-saving without causing major bleeding.
Case Report
The patient was a 67-year-old female (height 1.58 cm and weight 87 kg), with a history of type 2 diabetes mellitus and hypertension. No pathology was determined in the routine preoperative tests. Bilateral TKA was performed under spinal anesthesia, using a tourniquet, with a parapatellar medial incision to both knees. At 6 hours postoperatively enoxaparin sodium 4000 IU (Clexane 0.4ml) was administered subcutaneously as thromboprophylaxis. On the postoperative first day, dyspnea, tachypnea (34/min), tachycardia (132/min), and hypotension (70/30 mmHg) developed suddenly. The patient seemed distant but was conscious, and oxygen saturation was (SpO2) 60%.
As the preoperative tests of the patient were normal, the above-mentioned clinical findings were present, and major orthopaedic surgery had been performed, massive PTE was the first pathology that came to mind. With rapid coordination of the cardiology and thoracic departments, the patient was admitted to the surgical Intensive Care Unit (ICU). Supportive treatment was started immediately (monitorisation, and oxygen was administered with mask [3-4lt/min]). Until the diagnosis was confirmed, 0.8ml enoxaparin sodium 8000 IU (Clexan 0.8ml) was administered subcutaneously. In the patient monitorisation, there were findings of right ventricle failure on electrocardiography (ECG) (Figure 1). In the arterial blood gases, pH was determined as 7.32, PCO2 24.6 mmHg, PO2 56.8 mmHg, and acid-base status cBase(Ecf)c -12.6 mmol/L. In bedside echocardiography, right ventricle diameter was 36 mm (normal <25mm), pulmonary artery pressure was 70 mmHg (normal <30mmHg), and there were moderate-advanced tricuspid failure and widespread thrombus in the right ventricle. The recombinant human tissue-type plasminogen activator (rt-PA, alteplase = Actilyse 50 mg, Boehringer Ingelheim, Germany) 100 mg was administered as a 10 mg intravenous bolus within 1-2 mins, and the remaining 90 mg as an intravenous infusion within 2 hours.
On the bedside transthoracic echocardiography taken at the end of two hours, the thrombus was observed to have completely disappeared, the ventricle diameter was close to normal (28mm), pulmonary artery pressure decreased (32 mmHg), tricuspid failure regressed to a mild level, blood pressure was measured as 110/60 mmHg, pulse 105/min, and SpO2 94%. At three hours after the thrombolytic drug treatment, arterial blood gas values were measured as pH 7.42, PCO2 33.2 mmHg, PO2 99.1 mmHg, and acid-base status cBase(Ecf)c -2.6 mmol/L. On the second day (12 hrs after thrombolytic drug administration) enoxaparin sodium 2 x 0.8 ml was started. Multidetector-CT angiography, which could not be made earlier because the hemodynamics of the patient were not suitable, was performed on day 3 together with peripheral venous CT angiography. No thrombus was observed in the pulmonary artery – branches, and in the deep venous system of both lower extremities. After compression bandages were applied to the extremities and follow-up of bleeding, the Hemovac drain was removed 48 hours later, and venous compression ultrasonography taken on day three was normal in both lower extremities.
No major bleeding associated with the thrombolytic drugs was observed in the patient. There was a total of 300 cc blood from the Hemvac drain from the right knee and 350 cc from the left knee. No significant bleeding was determined at the operation site. Some ecchymosis was determined only in the knee region and the region of bleeding. Throughout the treatment, four units of erythrocyte suspension were administered. After five days of follow-up in ICU, blood pressure was measured as 119/61 mmHg, pulse 92/min, SpO2 95% (without mask), respiratory count 20/min, so the patient was transferred to the chest diseases ward in a good condition. Following removal of the sutures on day 13, 5 mg of oral warfarin was added to the 2 x 0.8ml enoxaparin treatment. When the International Normalized Ratio (INR) values reached 2-3, the enoxaparin was terminated, warfarin was continued at a dose of 3 mg, and the patient was discharged.
At the 3-month follow-up examination in the chest diseases department, ventilation/perfusion scintigraphy and venous compression ultrasonography in both lower extremities were normal, and therefore warfarin was terminated and ticlopidine (ticlocard 250 mg) was administered. Now in the 8th postoperative year, there has been no new DVT or PTE attack in this patient. The Knee Society arthroplasty evaluation knee score was determined to be 92 (excellent) and the knee function score was 90 (excellent). Written informed consent was obtained from the patient for the publication of this study.
Discussion
Massive PTE is a fatal complication of TKA, with reported mortality rates of 2-8% in cases with treated PTE and 25-30% in untreated cases. Difficulty in rapid and early diagnosis, the risk of bleeding from anticoagulants given before diagnosis, the time taken for diagnostic tests, and the bleeding complications of the thrombolytic drugs recommended in treatment, constitute a problem in PTE. It has been stated that >50% of the deaths of PTE patients occur in the first hour [1]. Therefore, action must be taken very rapidly. In the current case, the time from clinical suspicion to starting thrombolytic treatment was one hour.
To be able to cope with these difficulties, reduce the risks, gain time for diagnosis, and reach a correct diagnosis without stress in patients who have undergone a major orthopaedic operation such as TKA, PTE should first come to mind when there is sudden development of dyspnea, tachypnea, tachycardia, mental confusion, lateral chest pain, cyanosis, persistent hypotension, and shock, and the patient must be admitted immediately to surgical ICU, life support must be provided, and if there is a delay in diagnosis and no contra-indications, anticoagulant treatment should be started immediately [1]. If the hemodynamic status of the patient is not suitable and/or there is no opportunity to apply multidetector-CT angiography, bedside transthoracic echocardiography should be performed first. As the current patient did not have stable hemodynamics, bedside transthoracic echocardiography was performed first and thrombus was determined in the right ventricle.
The presence of right ventricle dysfunction, thrombus in the right atrium and/or right ventricle, and pulmonary hypertension on echocardiography is sufficient for a diagnosis of massive PTE. Echocardiography is the first procedure to be applied in patients with suspected PTE when multidetector-CT angiography cannot be taken [3]. When there is suspicion of PTE, if the patient is hemodynamically stable and multidetector-CT angiography can be taken, this method should be performed [4]. Bedside lower extremity compression ultrasonography should also be performed in patients with suspected PTE, if available. The presence of a thrombus on ultrasonography supports the diagnosis of PTE [5]. Despite DVT seen together with PTE at the rate of 16.9%-56.4%, it generally has an asymptomatic course, and the first symptoms associated with PTE in patients may be dyspnea, tachypnea, and tachycardia [4.5]. In the current patient, thrombus was determined on echocardiography, and additional tests of D-dimer, serum cardiac troponins, and natriuretic peptides were not considered to be necessary for the diagnosis of massive PTE.
If there is no contra-indication, thrombolytic drugs are the treatment approach first selected in the treatment of massive PTE [2]. Of the thrombolytic drugs available, recombinant human tissue-type plasminogen activator has the advantages of a shorter plasma half-life (2-6 mins) and duration of application (two hours) than other thrombolytic drugs. It is not necessary to terminate it before starting anticoagulants, and there are few bleeding complications despite the rapid administration [6]. The most significant side-effect of thrombolytic drugs is that they increase the risk of bleeding. These bleedings may be in the form of minor bleeding such as bleeding in the region of intramuscular injection or major bleeding such as intracranial, gastrointestinal, and retroperitoneal bleeding. The rate of major bleeding of thrombolytic drugs has been stated to be 3-21.7%, and intracranial or fatal hemorrhage as 1.8-3% [2,6]. Therefore, they must be used with great attention paid to the benefit-harm relationship. There are absolute and relative contra-indications to thrombolytic treatment. Having undergone major orthopedic surgery within the last 3 weeks is one of the absolute contra-indications [7]. However, as in the current patient, it may become a relative contra-indication in life-threatening massive PTE cases. As the hemodynamics of the current patient were not stable, and with the thought that the life of the patient could be lost with the preparation time for emergency surgery or percutaneous catheter embolectomy, thrombolytic treatment was considered correct and was therefore administered. No major bleeding occurred in this patient.
If thrombolytic drugs cannot be used in patients with massive PTE or if there is no response to treatment and conditions are suitable, these are indications for surgery or percutaneous catheter embolectomy [7]. However, it must not be forgotten that these procedures take time and carry risks. In patients with massive PTE with contra-indications for anticoagulant treatment, those who develop complications under treatment, or develop recurrence under anticoagulant treatment, the vena cava inferior filter is one of the methods that can be used. However, although the vena cava inferior filter is an effective alternative treatment method, it is not currently frequently used because of complications [1].
Conclusion
With early diagnosis followed by rapid and correct treatment, massive PTE may not be fatal. Time is of vital importance in PTE cases. By providing appropriate conditions for these patients, and taking precautions against bleeding complications, thrombolytic treatment can be applied and be life-saving.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Keller K, Hobohm L, Ebner M, Kresoja KP, Münzel T, Konstantinidies SV, et al. Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany. Eur Heart J. 2020;41(4):522-9.
2. Hao Q, Dong BR, Yue J, Wu T, Liu GJ. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2018;12(12):CD004437.
3. Dresden S, Mitchell P, Rahimi L, Leo M, Rubin-Smith J, Bibi S, et al. Right ventricular dilatation on bedside echocardiography performed by emergency physicians aids in the diagnosis of pulmonary embolism. Ann Emerg Med. 2014;63(1):16-24.
4. Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354(22):2317-27.
5. Goodacre S, Sampson F, Thomas S, van Beek E, Sutton A. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging. 2005;5:6.
6. Islam MS. Thrombolytic Therapy by Tissue Plasminogen Activator for Pulmonary Embolism. Adv Exp Med Biol. 2017;906:67-74.
7. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141( Suppl. 2):S419-96.
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Alikemal Yazıcı, Ümit Aygün. Pulmonary thromboembolism and thrombolytic treatment in total knee arthroplasty: A case report. Ann Clin Anal Med 2022;13(Suppl. 2):S144-147
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A case report of immediate autotransplanted teeth: 2-year follow-up
Tuğçenur Yıldız 1, Büşra Koç 2, Esra Mavi 2, Recai Zan 1
1 Department of Endodontics, 2 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Sivas Cumhuriyet University, Sivas, Turkey
DOI: 10.4328/ACAM.21259 Received: 2022-06-09 Accepted: 2022-07-13 Published Online: 2022-07-19 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S148-151
Corresponding Author: Tuğçenur Yıldız, Department of Endodontics, Sivas Cumhuriyet University, 58140, Sivas, Turkey. E-mail: dttugceyildiz@gmail.com P: +90 533 094 94 45 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2689-0622
Autotransplantation is the removal of tissue or an organ from an area of a living being’s body and its transplantation to another area in the same body. Autotransplantation plays a key role in replacing missing teeth of young patients since this procedure has many advantages compared to fixed prosthesis and implant applications in individuals of developmental age. General indications for autotransplantation are periodontal causes and tooth loss that cannot be restored due to caries or trauma. On the other hand, external root resorption and dentoalveolar ankylosis are the most common complications of autotransplantation. Autotransplantation is a treatment method that can result in a high success rate when attention is paid to the necessary prognostic factors.
Keywords: Atraumatic Extraction, Autotransplantation, CBCT
Introduction
Autogenous tooth transplantation, or autotransplantation is defined as the transfer of an impacted or erupted tooth from the region of the same individual to the surgically prepared socket or extraction space at the recipient site [1]. In the repositioning of donor teeth, the position of the teeth that are congenitally missing or have been lost due to reasons such as dental caries, trauma, and periodontal diseases is one of the most important criteria [2]. In the literature, the long-term success rate of autotransplantation has reached 93% [3]. It has been reported that many factors, such as the patient’s age, the type and root development level of the tooth to be transplanted, the compatibility between the tooth and the recipient site, atraumatic operation, postoperative stability and vertical height of the transplanted tooth, are effective in the success of autotransplantation before and after operation [4].
In this case report, we present the molar and premolar autotransplantations and follow-ups in two patients and the success rates of autotransplantation, factors affecting prognosis, and complication risks.
Case Report
Case 1:
In this case, the transplantation of the left third molar of a patient with a follow-up period of 2 years to the space of the first molar, which cannot be restored due to a vertical fracture in the same region, is explained.
A 24-year-old healthy female patient presented to the surgical clinic of Sivas Cumhuriyet University Faculty of Dentistry due to pain in her mandibular left first molar. In the intraoral and radiological examination, a vertical fracture was determined in tooth number 36, and tooth extraction was indicated (Figure 1A, 1B). It was decided that tooth number 38 without caries in the same region was suitable for transplantation, and the patient was informed about the transplantation treatment. After obtaining informed consent from the patient, tooth number 36 was extracted atraumatically without damaging the buccal bone under local anesthesia (Ultracain D-S Forte, Aventis, Turkey). Then, the third molar was extracted without contacting the root surface to prevent damage to the periodontal ligaments, and carefully placed in the socket of the first molar. The tooth was then positioned appropriately in the dental arch and sutured primarily. Thus, the tooth was also splinted. Afterward, the tooth was reduced from the occlusion by about 1 mm to avoid occlusal trauma (Figure 1C).
The patient was prescribed antibiotics (amoxicillin + clavulanic acid 1000 mg twice a day), analgesics (paracetamol 500 mg twice a day), and antibacterial mouthwash (benzydamine HCl + chlorhexidine gluconate). Sutures were removed 10 days after the operation, and endodontic treatment was applied.
In the postoperative 4th month, no mobility in the tooth and no signs of infection were observed in the clinical examination. In the radiographic examination, the onset of bone apposition was seen around the roots of the transplanted tooth, and there were no lesions. In the radiological examinations performed with cone-beam computed tomography (CBCT) in the postoperative 9th, 12th and 24th months, no signs of complications such as external root resorption and ankylosis were observed (Figure 1D, 1E, 1F).
Case 2:
A 20-year-old healthy male patient presented to the endodontics clinic of XXXX University Faculty of Dentistry for the examination of his mandibular left second premolar. In the intraoral and radiological examination, it was seen that tooth number 35 had undergone root canal treatment, and the amount of remaining tissue was insufficient to be restored (Figure 2A). Therefore, tooth extraction was decided. Tooth number 44, which was observed to be dysfunctional and outside the right lower arch, was found to be suitable for transplantation to replace the mandibular left second premolar (Figure 2B). After obtaining the informed consent from the patient, tooth number 35 was extracted atraumatically without damaging the buccal bone under local anesthesia (Ultracain D-S Forte, Aventis, Turkey). Then, the mandibular right first molar was extracted without contacting the root surface to prevent damage to the periodontal ligaments and placed carefully in the socket of the mandibular left second premolar (Figure 2C). The tooth was then positioned appropriately in the dental arch and sutured primarily. Thus, the tooth was also splinted. Afterward, the tooth was reduced from the occlusion by about 1 mm to avoid occlusal trauma.
The patient was prescribed antibiotics (amoxicillin + clavulanic acid 1000 mg twice a day), analgesics (paracetamol 500 mg twice a day), and antibacterial mouthwash (benzydamine HCl + chlorhexidine gluconate). Sutures were removed 10 days after the operation, and endodontic treatment was applied (Figure 2D).
In the postoperative 3rd month, no mobility in the tooth and no signs of infection were observed in the clinical examination. In the radiographic examination, the onset of bone apposition was seen around the roots of the transplanted tooth, and there were no lesions. In the radiological examinations performed in the postoperative 9th, 12th and 24th months, no signs of complications such as external root resorption and ankylosis were identified (Figure 2E, 2F).
Discussion
Autogenous dental transplantation can be described as the transfer of an autogenous tooth to the extraction socket of a tooth, which is congenitally missing or ectopically erupted, has crown damage, has a periodontal disease, has been traumatized, or has been extracted due to endodontic failure, or to a surgically prepared recipient site.
In the first case presented, the transplantation of the third molar tooth to the extraction socket of the mandibular left first molar with a poor prognosis (both in the same arch) is explained. In the second case, the transplantation of the mandibular right first premolar, which erupted ectopically, to the socket of the mandibular left second premolar with a poor prognosis (different arches) is explained.
The atraumatic extraction of the tooth to be transplanted in a way that will minimally damage the periodontal ligament and cement is among the important factors that influence the success of autotransplantation. Hence, contact with the root surface should be avoided during the extraction of the tooth to be transplanted. Manual contact with the tooth to be transplanted should be minimal to protect Hertwig’s epithelial sheath and pulpal tissues. Otherwise, root development may be prevented, and attachment loss, root resorption, or ankylosis may arise [5].
Inflammatory root resorption and dentoalveolar ankylosis are the most common complications after autotransplantation [6]. Considering that these complications might also develop in our cases, we used CBCT in the postoperative long-term follow-up of our cases to benefit from the advantages of CBCT mentioned in the afore-mentioned case reports in postoperative follow-ups and ensure accurate detection. In this context, no complications such as root resorption and ankylosis were observed in long-term postoperative follow-up tomography, and long-term success was achieved in the cases.
The shape and duration of fixation also influence resorption. Rigid fixation and prolonged fixation duration are reported to have an adverse effect on root length and prognosis. Handa and Handa [7] report that fixation is required for stability, there are compliance problems due to wisdom tooth morphology, the flap is tightly closed with suture fixation, new periodontal attachment is achieved, and bacterial invasion is prevented in the relevant region. Based on the results of the above-stated case reports, the transplanted teeth were fixed semi-rigidly with suture for two weeks in all our cases. In parallel with the results of other studies, we support the advantages of this approach in providing new periodontal attachment as a result of the 2-year follow-up. On the other hand, the absence of any radiolucent appearance, percussion sensitivity, or abscess formation at the root tip during this period indicated that this approach was also superior in terms of bacterial invasion.
Dioguardi et al. [8] state the parameters of evaluating the success of autotransplantation as follows: immobility of the transplanted tooth in the socket without any problem, functional and painless chewing, no mobility in the tooth, no pathological condition on radiography, normal appearance of the lamina dura on radiography, sulcus depth within normal limits, and normal gingival contour and color.
Conclusion
Autotransplantation is not an extensively used application, but it offers an alternative to implant and prosthetic treatments due to its advantages, such as being more economical and relatively simpler than different techniques, producing aesthetically and functionally satisfactory results, and maintaining the quality of the alveolar bone. However, it has also disadvantages such as the unpredictability of the treatment outcomes at times and the loss of the transplanted tooth due to probable complications.
Acknowledgment
The authors thank Asst. Prof. Ayşegül GÖZE SAYGIN for her contributions and constructive comments on the manuscript.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Ravi PK, Jyothi M, Sirisha K, Racca K, Uma C. Autotransplantation of mandibular third molar: a case report. Case Rep Dent. 2012;2012:629180.
2. Sugai T, Yoshizawa M, Kobayashi T, Ono K, Takagi R, Kitamura N, et al. Clinical study on prognostic factors for autotransplantation of teeth with complete root formation. Int J Oral Maxillofac Surg. 2010;39(12):1193-203.
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8. Dioguardi M, Quarta C, Sovereto D, Troiano G, Melillo M, Di Cosola M, et al. Autotransplantation of the Third Molar: A Therapeutic Alternative to the Rehabilitation of a Missing Tooth: A Scoping Review. Bioengineering. 2021;2:120.
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Tuğçenur Yıldız, Büşra Koç, Esra Mavi, Recai Zan.A case report of immediate autotransplanted teeth: 2-year follow-up. Ann Clin Anal Med 2022;13(Suppl. 2):S148-151
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Persistent falcine sinus with hypoplastic distal superior sagittal sinus and aplasia of transverse sinus
Hatice Kaplanoğlu 1, Aynur Turan 1, Ferhat Yıldırım 2, Veysel Kaplanoğlu 3
1 Department of Radiology, Health Sciences University, Dışkapı Yıldırım Beyazıt Training and Research Hospital, 2 Department of Radiology, Ministry of Health, Mamak State Hospital, 3 Department of Radiology, Health Sciences University, Ataturk Sanatory Educatıon and Research Hospıtal, Ankara, Turkey
DOI: 10.4328/ACAM.21368 Received: 2022-08-23 Accepted: 2022-09-25 Published Online: 2022-10-11 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S152-154
Corresponding Author: Hatice Kaplanoğlu, Department of Radiology, Health Sciences University, Dışkapı Yıldırım Beyazıt Training and Research Hospital, 06100, Ankara, Turkey. E-mail: hatice.altnkaynak@yahoo.com.tr P: +90 312 508 44 43 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1874-8167
Falcine sinus, located in falx cerebri, is a rare anatomical structure that closes after birth. A 40-year-old man was admitted to the hospital complaining about an intermittent headache and epileptic seizure that developed over the past 1 year. It was seen that persistent falcine sinus is related to hypoplasia of the posterior third of the superior sagittal sinus. Small calibrated collateral vascular structures were noted at the supratentorial level, especially between the right sulci and the interhemispheric fissure. The right transverse sinus was not observed. In this case report, a very rare combination of the persistent falcine sinus with dural sinus and gray matter anomalies was presented with literature and imaging findings.
Keywords: Persistent Falcine Sinus, Superior Sagittal Sinus, Straight Sinus, Embryology
Introduction
Falcine sinus, located between the dural sheaths of the falx cerebri in the embryonic period, is a normal anatomic venous structure and closes after birth [1]. Falcine sinus that does not close after birth is defined as persistent falcine sinus (PFS). It is not uncommon in the literature, however its association with complex anomalies is extremely rare [2]. PFS has been reported quite commonly in pediatric patients [3]. However, it is a rare vascular anomaly in adults [1,4]. Different studies have reported that PFS is mostly localized in the posterior falx cerebri, and it may be related to obstruction of the straight sinus (SS) or superior sagittal sinus (SSS). It can be seen with congenital vascular lesions such as Galen vein malformation, arteriovenous malformations, corpus callosum agenesis, acrocephalosyndactyly, and Chiari malformation [3]. Here, we present a rare case with hypoplastic distal SSS and right transverse sinus aplasia accompanying PFS in an adult.
Case Report
A 40-year-old man was admitted to the hospital complaining with an intermittent headache, clouding of consciousness, and epileptic seizures that developed over the past 1 year.
Cranial magnetic resonance imaging (MRI) (1.5-T Siemens Aera) (axial T1 weighted, axial and coronal T2 weighted, axial and sagittal FLAIR, DWI sequences) and magnetic resonance venography (MRV) (raw images obtained in the transverse plane with the contrast-enhanced 3D phase-contrast imaging method were processed by the MIP method) was revealed.
In Cranial MRI, encephalomalacia area in the right frontal lobe with hemosiderin pigments and dilatation of frontal horn of the right lateral ventricle was observed. (Figure 1a, b). The thickening of the meningeal structures in the right cerebral hemisphere, especially in the frontal region, was observed. In the right frontal lobe and superior temporal gyrus, an appearance compatible with pachygyria-polymicrogyria was detected (Figure 1c). In MRV SSS calibration is distinctly thin posteriorly and looks hypoplastic (Figure 2a). It was observed that the PFS extending from the middle part of the SSS towards the inferior continued as an SS-like vein and drained into the left transverse sinus (Figure 2b). Bilateral internal cerebral veins and basal vein of Rosenthal drained into PFS. Inferior sagittal sinus was not observed. Small calibrated collateral vascular structures were noted at the supratentorial level, especially between the right sulci and the interhemispheric fissure (Figure 3). Right transverse sinus and left Labbe vein were not seen. As a result of the findings, clinical and radiological follow-up was recommended to the patient.
Discussion
Falcine sinus (FS), located between the dural sheaths of the falx cerebri in the embryonic period, is a normal anatomic venous structure [4]. Falcine sinus that does not close after birth is defined as persistent, reopening of closed FS secondary to pressure in venous sinuses is also defined as recanalization [2]. In fetal life, between the cerebral hemispheres, the dorsal venous channels of the anastomotic venous structure called the sagittal plexus, located at the level of the primitive falx cerebri, turn into the anterior part of superior sagittal sinus, and the ventral section turns into the straight sinus and inferior sagittal sinus [1, 2]. With the development of the occipital lobe, the SSS and SS enlarge towards the occipital pole, allowing the SSS and SS to be fully formed. Falcine sinus is formed by one of the caudal anastomotic canals of the sagittal plexus and usually disappears after complete development of the SSS and SS [5].
The incidence of FS, PFS, recanalized FS is %5.3, %3.7 and %1.6, respectively, in a study on 1531 cases with thin-section contrast-enhanced 3D sagittal T1 scans, and MR venography showing that FS is not rare. According to this study, only three of the 57 PFS patients had complex congenital anomalies, two had rudimentary SS, and fifty-two patients had no anomaly accompanying PFS. Anomalies of straight sinus and SSS are usually associated with FS as a result of their embryonic relationships during the fetal period [2]. These anomalies usually include hypoplasia or absence of venous sinuses and the incidence is very low [2]. Aplasia or hypoplasia in the straight sinus can lead to an alternative venous pathway through the sagittal plexus to direct blood from the deep venous system to the superficial system [3]. Falcine sinus acts as an alternative pathway [4].
In one of the 3 cases with SS aplasia and reported to have PFS at different times before, there was atretic encephalocele and anterior cerebellar vermis atrophy in one [6], atretic encephalocele in the second [7], and temporal arteriovenous malformation in the third case [8]. In all three cases, PFS developed as a congenital variation. Absence or interruption of the straight sinus caused the persistence of falcine sinus [6-8]. Hypoplasia of the posterior third of the SSS, such as SS aplasia, can also lead to the development of PFS [1]. In this case report, hypoplasia of the distal SSS caused FS to persist.
Many congenital anomalies associated with PFS have been described. These are bifid cranium, Galen vein malformation, corpus callosum agenesis, Apert syndrome, pericallosal arteriovenous malformation associated with the absence of the posterior part of the corpus callosum, osteogenesis imperfecta, Chiari type II malformation, occipital encephalocele, parietal skull defect, meningoencephalocele, absent or dysplastic tentorium cerebelli, midbrain arteriovenous malformation, and bilateral giant parietal foramina [3, 5, 6].
Increased pressure within the venous sinuses can lead to the recanalization of potential venous channels such as falcine sinuses. External causes of increased internal pressure of venous sinuses are tumor compression (especially those close to the meninges and closely related to the venous sinus), and pressure on the venous sinuses of thickened meninges due to hypertrophic meningitis. The internal cause is venous sinus thrombosis [2].
In the case presented here, there were hypoplastic distal SSS, aplasia of inferior sagittal and right transverse sinuses, small calibrated collateral venous vascular structures accompanying PFS. At the same time, an appearance compatible with pachygyria-polymicrogyria was observed in the right frontal lobe. This association supports that the presence of PFS in our case is congenital.
Conclusion
Persistent falcine sinus is not a quite rare anatomic variation, it can be seen in different age groups, children, and as well as adults. It may not always be related to complex craniocerebral anomalies. However, when it occurs, it may be associated with congenital and acquired anomalies in the superior sagittal sinus or straight sinus. FS and accompanying anomalies will be better understood and diagnosis will be easier with the help of the high soft-tissue resolution of MRI.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
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2. Lin L, Lin JH, Guan J, Zhang XL, Chu JP, Yang ZY. Falcine Sinus: Incidence and Imaging Characteristics of Three-Dimensional Contrast-Enhanced Thin-Section Magnetic Resonance Imaging. Korean J Radiol. 2018;19(3):463-9.
3. Sener RN. Association of persistent falcine sinus with different clinicoradiologic conditions: MR imaging and MR angiography. Comput Med Imaging Graph. 2000;24(6):343-8.
4. Strub WM, Leach JL, Tomsick TA. Persistent falcine sinus in an adult: demonstration by MR venography. AJNR Am J Neuroradiol. 2005;26(4):750-1.
5. Kesava PP. Recanalization of the falcine sinus after venous sinus thrombosis. AJNR Am J Neuroradiol. 1996;17(9):1646-8.
6. Cho J, Kim MY, Roh HG, Moon JW. MR images of spontaneously involuted atretic cephalocele concomitant with persistent falcine sinus in an adult. J Korean Soc Magn Reson Med. 2006;10:117-20.
7. Kim JH, Cho JM, Jung JM, Park ES, Seo JH, Lim JY, et al. Two cases of congenital atretic encephalocele misdiagnosed as dermoid cyst. Korean J Pediatr. 2006;49(9):1000-4.
8. Won JB, Park SH, Hong JW, Kim YK, Shin MJ, Baik SK, et al. Radiologic findings of deep seated cerebral arteriovenous. J Korean Radiol Soc. 1999;41(2):235-9.
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Tracking cancer in Morocco: A systematic review
Zakariae Cherrat 1, Rachid Razine 1,2, Nada Bennani Mechita 2,5, Hayat Sine 3, Abderrahmane Achbani 6, Redouane Abouqal 2,4, Majdouline Obtel 1,2
1 Department of Public Health, Laboratory of Community Health, Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, 2 Department of Biostatistics, Clinical Research and Epidemiology (LBRCE), Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, 3 Department of Laboratory of Medical Biology, Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, 4 Department of Medical Emergency, Ibn Sina University Hospital Center, Rabat, 5 Directorate of Epidemiology and Diseases Control, Ministry of Health Morocco, Rabat, 6 Department of Biology, Laboratory of Cell Biology and Molecular Genetics, Faculty of Sciences, University Ibn Zohr, Agadir, Morocco
DOI: 10.4328/ACAM.21030 Received: 2022-01-13 Accepted: 2022-02-15 Published Online: 2022-03-17 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S155-162
Corresponding Author: Zakariae Cherrat, 21, Crown Prince City, Inezgane, Morocco. E-mail: cherrat.zakariae@gmail.com P: +21 266 215 50 65 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1463-0874
Aim: The aim of this systematic review is to study the epidemiological, risk factors and socio-economic characteristics of cancer in Morocco.
Material and Methods: A protocol for conducting our systematic review was developed according to the guidelines of “Preferred reporting articles for systematic reviews and meta-analysis”. Several databases and the WHO clinical trial registries were consulted. A period from March to June, 2020 was devoted to this consultation. The protocol of the review was registered in the PROSPERO.
Results: Forty-Four studies were selected. The age of the study population ranged from 5 to 62 years. We found a predominance of patients living in urban areas, a high frequency of illiterate and a predominance of married patients. Cancer was more prevalent among the social group with limited health insurance. Smoking, obesity/overweight and family history were identified as risk factors for cancer. Cancers were diagnosed at advanced stages, mainly for colorectal, digestive, lung and cervical cancers.
Discussion: Cancer in Morocco affects the young, underprivileged and uninsured population with a marked delay in diagnosis. Finally, it is recommended to study the factors of delayed diagnosis and to make more efforts in prevention and early detection in order to reduce the incidence of cancer in our country.
Keywords: Epidemiological Profile, Risk Factors, Socioeconomic Characteristics, Morocco
Introduction
In Morocco, cancer has become a public health issue [1]. The extent of the disease has become more important, with 30,000 to 40,000 new cases being detected each year [2]. The pathogenesis of cancer is multifactorial, with a proportion attributable to lifestyle and individual risk factors. Cancer is a disease of social incidence due to its socio-economic effects that affect both the patient and his or her social environment. In recent years, several studies have attempted to define cancer incidence rates and estimate its epidemiology in several populations. While the literature is extensive, the incidence ranges reported are frequently inconsistent, reflecting the biases in patient recruitment, sampling procedures, and types of instruments employed. Incidence studies are important for use in the planning of health care and epidemiological investigations, because they provide important information to estimate theburden of disease in a population. This systematic review aims to study the epidemiological profiles of cancer, the socio-demographic and socio-economic characteristics of incident cases of cancer in Morocco and the risk factors of this disease.
Material and Methods
Research Strategy
A protocol for conducting our systematic review was developed according to the guidelines of “Preferred reporting articles for systematic reviews and meta-analysis” (PRISMA. 2009) [3]. This protocol was registered in the international prospective register of systematic reviews (PROSPERO: CRD42020173657). In order to identify studies relevant to this review, several databases were independently searched by two reviewers (ZC and RR): Science Direct, PubMed, Clinicalkey, Web of Science, EMBASE, LILACS, GLOBAL Health and Proquest. The search had no language restrictions. WHO clinical trial registries were also consulted. The keywords used were as follows: (cancer incidence) or (trends in cancer incidence) or (increase in new cancer cases) and (epidemiological patterns of cancer) or (epidemiological aspects of cancer) or (epidemiological characteristics of cancer) or (socio-economic characteristics of cancer patients) or (socio-economic characteristics of incident cancer cases) and (individual risk behaviours) or (individual risk factors) and (Morocco) or (the Kingdom of Morocco) or (cities in Morocco).
Criteria for inclusion:
• Studies on cancer in the Moroccan population, published between 2010 and 2019.
• Studies that have looked at the epidemiological patterns of cancer.
• Studies that have studied the socio-demographic characteristics of incident cancer cases in Morocco.
• Studies that have addressed risk factors for the disease including smoking, alcohol consumption, obesity and family history.
Exclusion criteria:
• The studies, which studied the anatomical profiles of cancer.
• Studies that were published in non-scientific journals
Evaluation of the Quality of Studies
A critical assessment of the quality of the selected studies was conducted by two observers (ZC and RR) using the following tools: “Critical Appraisal Skills Program (CASP) Case-Control Study”, “Critical Appraisal Skills Program (CASP) cohort study”, “Quality Assessment Tool for Case Series Studies”, and “Quality Assessment Tool for Cross-Sectional Studies”.
Data extraction
Two reviewers (ZC and RR) independently extracted the data using a form designed for this purpose, based on COCHRANE’s guide “Data collection form for intervention reviews”. The extracted data includes epidemiological patterns of cancer, socio-demographic and socio-economic characteristics of patients (age, sex, place of residence, level of education, marital status, health insurance, socio-economic level). For risk factors, we extracted consumption of both alcohol and tobacco, obesity/overweight, and family history.
Results
Our search resulted in the selection of forty-four articles (n=44) (Figure 1).
With respect to study type: (n=10) were prospective control cases, (n=6) were retrospective case series, (n=3) were retrospective cross-sectional studies, (n=1) was a retrospective cohort study, (n=18) were retrospective studies, and (n=6) did not specify study type. About the study location: Rabat (n=14), Casablanca (n=5), Fez (n=9), Oujda (n=5), Meknes (n=1), Marrakech (n=2),
Casablanca and Rabat (n=5), Marrakech and Casablanca (n=1), and two multicenter studies (n=2). All studies were conducted in the hospital setting. For the sampling, only one study (n=1) defined the sampling method and sample size. This research included people of all ages [4]. With regard to ethical considerations: (n=16) studies obtained ethics committee approval, and (n=15) had signed informed consent from patients.
The quality of the selected studies was rated as “good”. For the case-control studies, the average score was 9.1/11.
Socio-demographic and socio-economic characteristics of cancer patients
Age
Regarding the age of the study population of the selected articles, twenty-nine (n=29) studies showed an average age ranging from 8.28 to 61 years. The studies of Karkouri et al., (2010), Harmouch et al., (2012) and Hazmiri et al., (2018) had a very young study population, with an age range between 5 and 19 years [5,6,7] . Twelve studies (n=12) calculated a median age ranging from 45 to 62 years. Two studies (n=2) specified neither the average nor median age [8, 9] (Table 1, 2).
Sex
Twenty-one studies (n=21) looked at female cancer. The sex ratio was calculated in fifteen studies (n=15); male predominance was reported in thirteen studies (n=13) with a sex-ratio ranging from 0.88 to 2.5. In the study by Benlahfid et al. (2017), a male/female ratio was less than 1 (0.88) [10]. (Tables 1,2).
Areas of residence
Fifteen studies (n=15) studied the residential environment of cancer patients: thirteen (n=13) reported a predominance of patients from urban areas with a rate between 59.2 and 80%. Two studies (n=2) by Berraho et al. (2017) and Imad et al. (2019) found a significant difference between the two settings [11, 12]. (Tables 1,2).
Level of education
Ten studies (n=10) examined patient education [4, 8, 11-18]. They revealed a predominance of illiterate patients with a rate between 47.56 and 84.4% (Table 1). An association between patients’ lack of schooling and increased risk of cervical cancer was reported in the study by Berraho et al., (2017) [11].
Marital status
This variable was examined in twelve studies (n=12). Married status predominated in all of these studies. It ranged from 56.6% reported in the study by Berraho et al. ( 2012) [4] , to 81% reported in the studies by Maamri et al. (2011) [9] and Imad et al (2019) [15]. A significant difference between different marital status was reported in the study by Berraho et al. (2017) [11].
Socio-economic level
Seven studies (n=7) analyzed the socio-economic level of patients [4,8,9,11,12,14,17]. It was considered low in all studies with a percentage between 64 and 92.2. Two studies (n=2) reported low monthly income for patients [12,17]. The study by Berraho et al., (2017) showed the low socio-economic level (83.5%) by specifying the rate of unemployed patients (91%) [11].
Health Insurance
Four studies reported the issue of patient medical insurance [4,8,11,13]. The rate of patients with health insurance did not exceed 15% in all four studies. The study by Imad et al., (2019) found that 77.33% of the study population was affiliated to the medical assistance scheme [12].
Proportion of cancer risk factors in Morocco according to selected studies
We limited ourselves to the following four risk factors: smoking, alcohol consumption, obesity/overweight and family history. Thirteen studies (n=13) examined a single risk factor [4,9,11,13,19-27], (n=4) studies reported two factors [14,28-30], three risk factors were addressed in (n=3) studies [10,16,17], and (n=2) studies reported all four risk factors [15,31].
Twelve studies (n=12) reported smoking as a risk factor for cancer with a percentage from 2.1 % to 86.15%) [10,11,14-19,24,26-28]. It is strongly associated with lung cancer in the study by Belmokhtar et al., (2019) [19]. The study conducted in Fez by Khalis et al., (2018) showed a very high proportion of passive smokers (44.7%) [17]. Alcohol consumption was reported in (n=5) studies, with a percentage from 1.69% to 17.4%) [10,14-16,31]. A statistically non-significant inverse association was reported in (n=4) studies between alcohol consumption and the risk of developing cancer [10,14,16,31]. Obesity/ overweight was reported in (n=7) studies: (9.7-46.8%) for obesity and overweight (32.3-53%), respectively [15,17,22,23,29-31]. Fourteen studies (n=14) addressed the family history of cancer. It was between 0.64 and 22.6% (Table 3).
Epidemiological profile of cancer patients in Morocco according to the studies analyzed
The epidemiological profile of cancer patients was explored in (n=36) studies. Histologic type was revealed in (n=28) studies, age at diagnosis in fourteen studies (=14), twenty-four specified the stage of the tumor, and (n=7) studies showed medical and/or surgical history of patients.
Histological type by cancer site
In studies investigating lung cancer, adenocarcinoma was the most common histological type (40.2-59%) [19,27,32]. For colorectal cancer, Lieberkühnien adenocarcinoma was predominant (82-97%) [15,33]. For breast cancer in both sexes, Infiltrating Ductal Carcinoma (IDC) was common with a proportion ranging from 86 to 96.4% [25,34-39].
Age of patients at the time of diagnosis
Age at diagnosis ranged between 5 and 71.1 years. The average age at highest diagnosis (71.1 years) was found in patients with colorectal cancer [33]. For pediatric tumours, the age of the children at diagnosis ranged from 5 to 9.3 years [5,7].
Tumor staging
Colorectal Cancer:
According to the study by Belhamidi et al. (2018), 55% of the population studied had stage II colorectal cancer [33]. Two studies (n=2) attributable to Imad et al. (2019), found advanced stages of colorectal cancer: (40% stage III and 36% stage IV) in the first study (54.65% stage III and IV) in the second [12,15].
Lung cancer:
Tumors were diagnosed at advanced stages (stage III and IV) [19,27,32]. The study by Belmokhtar and al. (2019) reported a proportion of 97% of patients with stage III and IV lung cancer [19]. The study by Obtel and al. (2015) found a significant difference between the two sexes [18].
Breast cancer:
The study by Obtel et al. (2015) found a predominance of stage II patients (59%) [18]. In two studies (n=2), the frequency of patients with stage II breast cancer ranged from 56 to 61.1% [30,34]. For stages II and III, the proportion of patients ranged from 77.8 to 82% [37,38].
Cervical cancer:
Patients were identified in the Obtel Study (2015) as stage III (65.7%) [18]. In addition, the study by El Majjaoui et al. (2016) classified patients with advanced cervical cancer in stages III and IV (88%) [40].
Medical and Surgical History
Diabetes was reported in (n=4) studies [10,15,19,26]. It was between 4.6 and 46.7%. Hypertension was identified in two studies (n=2), with a proportion between 2.44 and 42.6% [10,19]. The study by Benlahfid et al. (2017) found a surgical history in the study population (34%) [10]. In addition, the study by Berraho et al. (2017) on cervical cancer showed the existence of Sexually Transmitted Infections (STIs) in 92.5% of the study
population [11].
Discussion
According to the results of our review, cancer in Morocco affected the young population. It appeared at an average age between 8.3 and 62.0 years. Our review revealed a high male sex ratio. Among 19 studies of both sexes, 13 reported male dominance. This may be due to the difference between the high global incidence of cancer in men compared to women.
The studies, subjects of our review, reported a high predominance of illiterate patients between 47.6 and 84.4%. This may be explained by the fact that illiterate patients do not seek early detection of cancer. Another study conducted in Tunisia confirmed that the level of education was an obstacle to cancer detection [42].
Regarding socio-economic status, we found a high percentage of patients with a low socio-economic status (64.0-92.2%). In addition, the studies by Berraho and al., (2017) and EL Amrani et al., (2018) reported a significant association between low socio-economic status and the risk of cancer occurrence [11,14].1st study: OR=2,2; 95% CI 1,2-3,9 and 2nd study: OR= 3,82;95% CI (1,38-10,55). These results were corroborated by a study in France, which attributed several types of cancers to low socio-economic status [43]. Thus, the study by Errahhali et al., (2017) reported 83.4% of unemployed patients [8] and 80% were poor according to another study [9]. The study by Khalis et al., (2018) showed that 40.9% of patient households had a monthly income below 2000 MAD [17]. Low socio-economic level, in our context, is a determinant of cancer occurrence and a barrier to access to diagnosis and treatment.
With regard to health insurance, our review found a very low proportion of patients with medical coverage, no more than 15%. The study by Imad et al. (2019) found a high frequency (77.33%) of patients affiliated to the medical assistance system (RAMED) [12]. This can be explained by the fact that a high proportion (78.4%) of the employed workforce in Morocco is not subject to any health insurance organism.
The pathogenesis of cancer is multifactorial. Lifestyle or behavioural factors are no longer in evidence today. Smoking is a major known cause of cancer-related deaths worldwide. In addition, a causal link has been established between smoking and twelve types of cancer [44]. In our review, smoking was considered a risk factor for several types of cancer. Indeed, the study by Belmokhtar et al. (2019) reported a highly significant association between tobacco consumption and lung cancer [19], with a significant difference between sexes (p< 0,001). A study conducted in the United States of America (USA) in 2014 supported our results, reporting that ¾ of incident cancer cases were smokers, with a high proportion of smokers for lung cancer (81.7%) [45].
Concerning alcohol consumption, the results of our review showed low frequencies of alcohol consumption among the populations studied (1.69-17.4%). Several studies, subjects of our review, reported a non-significant inverse association between alcohol consumption and the risk of cancer. Our results are different from those confirmed by a French study, which showed that alcohol was the cause of 28,000 new cases of cancer. The same study found that 57.7% of esophageal cancer and 48.0% of liver cancer were attributable to alcohol [46]. In addition, a review of the literature concluded that the risk of cancer becomes greater if there is a synergistic interaction between alcohol consumption and smoking [47].
Evidence of a causal link between obesity and the development of cancer has been established [48]. Several epidemiological studies have correlated overweight with an increased risk of cancer occurrence in various locations [49]. In this regard, the results of our review revealed high frequencies of obesity (9.7-46.7%) and overweight (32.3-53.0%) in the populations studied. The idea behind this confirmation is the high prevalence of obesity (14%) and overweight (30%) in the Moroccan population [50]. An American study came to support our results, revealing a significant proportion of cancer (7.8%) attributable to obesity [45].
With respect to family history of cancer, several epidemiological studies have shown their association with an increased risk of developing cancer [51]. The shares attributable to family history were proportional to the location of cancer. It was 5-10% for breast cancer [52], 2.0-9.4% for colon cancer and 4.6-9.5% for prostate cancer [51]. The results of this review reported a frequency of patients with a family history ranging from 0.64 to 22.6%. Some characteristics of cancer patients in relation to family history have been revealed in this study.
In regard to the cancer epidemiology profile, we looked at four elements: histological type, average age at diagnosis, staging, and medical history of cancer.
For lung cancer, adenocarcinoma was the most common histological type (40.2-59.0%). This can be explained by variations in smoking behaviour and the new composition of cigarettes. Moreover, in 2015, adenocarcinoma was the predominant histological type in Tunisia (46.3%) [53].
As for colorectal cancer, a highly elevated frequency of Liberkuhnian adenocarcinoma has been reported in our review. Our results were consistent with a French study, which confirmed that more than 95% of colorectal.
For breast cancer, our review revealed that infiltrating ductal carcinoma was the most common (86- 96.4%). These results were identical to those found in a Tunisian study for breast cancer, where the frequency of ductal infiltrating carcinoma was 94.6% [54]. For cervical cancer, our review reported a high frequency of squamous cell carcinoma (94.0%). The situation was similar in the Maghreb countries, in both Tunisia and Algeria, squamous cell carcinoma was the most frequent histological type in cervical cancer patients, with 86.2% and 90.5% respectively [55]. In addition, we found that breast and cervical cancer accounted for 56.3% of female cancers [18].
Cancer in Morocco was diagnosed at a young age, 67.0% were under 50 years of age [18]. Indeed, for breast cancer, two studies reported a young age (46.0-46.8 years). This can be explained by the policy of early detection of breast cancer envisaged by the Ministry of Health in Morocco.
The highest average age at diagnosis in our review was found in patients with colorectal cancer. This can be explained by the fact that colorectal cancer is a specific tumor of the elderly with recourse to late diagnosis.
Concerning the staging of tumors, 2/3 of the studies that looked at colorectal cancers revealed a predominance of tumors classified in advanced stages (III and IV). Lack of knowledge of the symptoms associated with this type of cancer may explain the delay in diagnosis.
For lung cancer, the studies, subjects of our review, showed a highly elevated frequency of patients diagnosed at advanced stages (III and IV). This may be explained by the late onset of symptoms indicative of the disease. Our results were corroborated by a Tunisian study, which reported a high frequency of patients with lung cancer classified as advanced (IIIB and IV) [56].
The results of the studies analyzed, in relation to breast cancer, reported a predominance of diagnosed tumors oscillating between intermediate stages (I and II) and stage III. This comes back to the policy of early detection of breast cancer undertaken in Morocco for several years. The results of our review were inconsistent with those of Canada, where 70% of breast cancer cases are diagnosed early, at stages I and II [57].
For breast and cervical cancer, our review identified a delay in screening for cervical cancer, stage III and IV. This type of cancer is much more related to underprivileged social classes, which can be explained by difficulties in accessing early screening despite the efforts made.
For pancreatic cancer, we have identified 59.3% of patients diagnosed at stage IV. These results are identical to those in Canada, 57% of pancreatic cancer cases were Stage IV [58]. This can be explained by the fact that most pancreatic cancers are not related to a preventable risk factor, and the tumor causes noticeable symptoms only in advanced stages.
As for medical history, several epidemiological studies have established an association between certain diseases and cancer. In this sense, the study by Gariani et al., (2010) confirmed a high frequency of certain cancers in the case of diabetes. Pancreatic cancer has been found in diabetics (80%), bladder cancer (40%) [59]. Similarly, diabetes increases the risk of colorectal cancer by 1.2 to 1.5 times [58]. The results of our review were consistent with those reported above. Diabetes was found in patients with colorectal cancer (19%) [15], gastric cancer (46.7%) [10] and pancreatic cancer (6%) [26]. The association between diabetes and risk of colorectal cancer occurrence can be explained by hyperinsulinemia and exposure to carcinogenic agents for the intestinal mucosa, caused by a longer intestinal transit time [59].
Concerning Arterial Hypertension (AHT), two studies in our review reported the presence of Arterial Hypertension in the populations studied: the first found a high frequency of Arterial Hypertension in patients with digestive cancer (42.6%) [10], and the second study reported 2.44% in cases of lung cancer [19]. In these two studies, AHT was found in parallel with diabetes. The presence of AHT in cancer patients can be explained by the behavioral risk factors favoring both cancer and high blood pressure (obesity, alcohol, tobacco, physical inactivity, etc.).
Regarding the history of sexually transmitted infections, the study by Berraho and al. (2017), part of our review, found a high frequency of STIs (90.2%) in patients with cervical cancer [11]. These results were corroborated by a study conducted in Africa on cervical cancer, which found a high frequency of STIs (70.2%) in patients with cervical cancer [60]. This may be due to the Human Papilloma Virus (HPV) responsible for STIs.
Limitations
Our systematic review has some limitations. Cancer studies did not cover all regions of the country. No studies included in this review were conducted in the northern and southern regions of Morocco. In addition, despite data from Casablanca and Rabat registries, these studies were carried out only in university hospital centers; none of these studies considered either regional centers or private oncology centers.
Conclusion
The studies analyzed showed particularities of cancer in Morocco. Most of the population affected by cancer was young, with low-income levels and a gender predominance of males.
Several types of cancer in Morocco are diagnosed at advanced stages compared to Western countries. It is highly recommended to study the factors behind the delay in diagnosis and how to deploy more efforts in the prevention and early detection in order to reduce the incidence of cancer in the Moroccan population.
Acknowledgment
The authors would like to thank Professor Abdelmadjid Redouane (Ibn Zohr University, Agadir, Morocco) for his assistance in reviewing the quality of the English manuscript.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Download attachments: 10.4328.ACAM.21030
Zakariae Cherrat, Rachid Razine, Nada Bennani Mechita, Hayat Sine, Abderrahmane Achbani, Redouane Abouqal, Majdouline Obtel. Tracking cancer in Morocco: A systematic review. Ann Clin Anal Med 2022;13(Suppl. 2):S155-162
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P53 as an important diagnostic biomarker in gall bladder neoplasms
Anshoo Agarwal 1, Yanina Singh 2, Naglaa A Bayomi 3-4, Afaf Taha Ibrahiem 5-6
1 Department of Pathology, Northern Border University (NBU), Arar, Kingdom of Saudi Arabia, 2 Department of Paediatrics and Preventive Dentistry, School of Dental Sciences, Sharda University, Greater Noida, India, 3 Department of Anatomy, Faculty of Medicine, Northern Border University (NBU), Arar, Kingdom of Saudi Arabia, 4 Department of Histology, Faculty of Medicine, Tanta University, Tanta, Egypt, 5 Department of Pathology, Faculty of Medicine, Northern Border University (NBU), Arar, Kingdom of Saudi Arabia, 6 Department of Pathology, Faculty of Medicine, Mansoura, Egypt
DOI: 10.4328/ACAM.21154 Received: 2022-03-22 Accepted: 2022-05-27 Published Online: 2022-07-29 Printed: 2022-10-20 Ann Clin Anal Med 2022;13(Suppl. 2):S163-167
Corresponding Author: Yanina Singh, Department of Paediatrics and Preventive Dentistry, School of Dental Sciences, Sharda University, 201310, Greater Noida, India. E-mail: yaninasingh@yahoo.co.in P: + 91 963 455 75 87 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6174-1011
Gallbladder carcinoma (GBC) is considered a fatal but seldom occurring cancer of the digestive tract. The process through which a gall bladder adenoma progresses to carcinoma is still unclear. Also, GBCs are seen to appear from pathways comprising metaplasia or dysplasia or from pre-existing adenomas. The only chance of cure is early diagnosis yet despite advances in imaging modalities it seems impossible. Biomarkers are considered an indicator of a biological state. The p53, biomarker lies among rapidly mutated tumor suppressor genes in neoplasms. p53 serves as a scout, which checks for abnormal cell growth against cancer in most of the cells. Proto-oncogenes and the tumor-suppressor genes are considered important factors in the development and prognosis of gallbladder neoplasms. P53 has also been found in gallbladder carcinomas in various studies.
Keywords: Gallbladder Carcinomas, Biomarkers, p53, Molecular Marker, Protein Expression
Introduction
Gallbladder carcinoma (GBC) is regarded among the most widespread malignancies of the biliary tract. [1] Various regions with the remarkably high incidence include Central and South America (Mexico, Chile, and Bolivia), Japan and Central and Eastern Europe (Hungary, Czechoslovakia, Poland, and Austria). Even with the use of advanced techniques, the survival rate of the patients is low compared to other carcinomas. Also, it has been seen that although the disease has a low incidence, it is usually diagnosed at later stages. [2,3] Preoperative clinical and radiological staging were essential procedures for determining the prognosis of GBC but lately, many practitioners do not find the use of conventional diagnostic methods helpful and they are not able to accurately stage the disease. [4] Characteristics of advanced malignant lesion include localized invasion, distant metastasis, extensive regional lymph node metastasis and vascular encasement due to these features, complete surgical resection is not possible. Hence, the only curative option available is complete resection at an early stage of the disease but only minimal patients report at an early stage. [5] Therefore, here comes the role of a reliable biological marker, which will act as a valuable diagnostic aid, thus helping in facilitating proper treatment plan and providing holistic care to the patients.
Methodology:
Various articles from the online sources like Pub Med, MEDLINE, GOOGLE Scholar were studied and evaluated for establishing the role of Biomarker p53 in the carcinoma of Gall bladder.
Cell growth cycle
The trademarks of tumour are unrestricted cell growth and proliferation occurring mainly due to loss of command over cell cycle checkpoints. The group of cyclins, cyclin-dependent kinases (CDKs), and their inhibitors (CDKIs) monitors the cell cycle by the event of activation and inactivation of phosphorylation. [6] The aggregation of numerous genetic variations leads to the development of GBCs, and out of these variations, disruption of cell cycle control is a key character. It often appears as poor regulation of cyclin protein expression, raised activity of cyclin dependent kinases, change in the expression or functioning of cyclin-dependent kinase inhibitors and transformation of cell cycle checkpoint control. [7] Also, the results have shown the involvement of suppressor genes, oncogenes and DNA repair genes, along with changes at molecular levels like epigenetic alterations and microsatellite instability. [8]
Molecular and genetic basis of gallbladder cancer
In the histologic analyses of GBC specimens, a stepwise progression from hyperplasia-atypical hyperplasia, metaplasia-dysplasia, or gallbladder adenomas to carcinoma is seen. Two distinct pathways were suggested related to GBC’s.[9] The first one is via adenoma-carcinoma sequence, excluding p53, K-ras or APC gene mutations, and the second pathway is de novo, where there is frequent p53 alteration related to low K-ras mutation percentage. [10] As previously mentioned, activation of cellular genes occurs along with inactivation of tumor suppressor genes that leads to the development of cancer. [11]
Molecular studies conducted in this field have shown that there is allelic loss of different chromosomal locations seen in GBC. The results from various studies also suggested the involvement of multiple tumour suppressor genes in the pathogenesis of GBC [12] (Figure 1). Mutations of the p53 gene are genomic aberration that has been detected among approximately 27%–70% of gallbladder carcinomas. [9]
Biomarker in GBC
A ‘biomarker’ can be described as a biological marker that converts into a state or expression of a protein that is consistent with the possibility of progression of the disorder or with the susceptibility of the disorder for the ongoing treatment. Biomarkers help in providing information regarding healthy and pathologic states along with monitoring the response to therapeutic intervention. When a biomarker establishes its validity, it can be further used for determining the risk of the disease, diagnosing the disease in an individual and to formulate a suitable treatment plan for the patient. Biomarkers can also be categorized as predictive and prognostic markers. A predictive marker is used to identify individuals who are more likely than similar individuals without the biomarker to experience a favorable or unfavorable effect from exposure to a medical product or an environmental agent, for example, the Human leukocyte antigen allele (HLA)–B*5701 genotype can be used for determining the human immunodeficiency virus (HIV) patients before abacavir treatment, i.e., to check patients who are at risk for developing serious skin allergies or reaction. Whereas, prognostic markers are used to identify the likelihood of a clinical event, disease recurrence or progression in patients who have the disease or medical condition of interest example Breast Cancer genes 1 and 2 (BRCA1/2) mutations can be used to assess the probability of development of a second breast cancer when evaluating patients with breast cancer. [13]
A tumor marker is a biomarker that is produced by cancer or tumor cells, it can be defined as “a substance expressed either by a tumor or by the host body in response to a tumor and that helps in cancer detection and monitoring”. Tumor markers are normal endogenous by-products that are secreted at a higher amount by cancerous cells or are the result of active genes that are at a dormant state in healthy cells. The presence of cancer can be detected through these markers as these are produced in significant amounts by cancerous cells.
Their presence can be marked in the tissues as an intracellular substance or these can be seen in the body serum. Their presence can be measured in various body fluids and in the serum. [14, 16]. (Table 1)
About p53 biomarker
p53 is an antioncogene and its mutation is detected on the short arm 17 encoded as 53-kD nuclear phosphoprotein that acts as an inhibitor of cell proliferation and is also a transcription factor. [17, 18] p53 is a nuclear transcription factor and transactivates various genes that are involved in the initiation of cell cycle arrest and/or apoptosis. Lower levels of p53 are expressed, normally caused by proteasomal degradation mediated majority by RING-finger type E3 ubiquitin protein ligase MDM2, which is a functionally latent form. When DNA damage occurs, p53 gets accumulated in the nucleus of cell via post-translational modifications like acetylation and phosphorylation. [19]
Structure of p53 (Figure 2)
p53 is made of various components including [20]
1. NH2-terminal acidic transactivation domain; N- terminal (NT)
2. DNA-binding domain; core domain and
3. Tetramerization (Tet) domain, and
4. C-terminal (CT) domain
Results
Table 1 depicts various biomarkers involved in Gall bladder carcinoma.
Discussion
Activation of P53 and its pathway
DNA can be altered by various methods like adding an alkyl group to various bases, loss of purine or pyridine or by oxidative free radicals’ reaction. The cells employ a different detection and repair mechanism for the damaging agent. Enzyme activities occur as a reaction to these DNA damages that detect and repair the DNA. Activation of enzyme activities occurs due to DNA damage, causing modification in the p53 protein at the level of amino-acid residue. These enzymes communicate with the p53 protein that damage has been occurred in DNA, hence, post-translational modifications take place that lead to ubiquitination, phosphorylation, methylation, acetylation or sumoylation of the biomarker. On determining the stress posttranslational alteration occurs through the media of these signals, which are transmitted to proteins and processed by a code. [33] (Figure 3)
The alterations in p53 protein caused by protein modifications represent in two ways. In the first way, it is seen that protein’s half-life in the cells raises from 6-20 mins to hours resulting in 3-10 folds increase in the protein concentration in a cell. Second, binding capacity of p53 to certain DNA sequences is increased, which advances the transcription of genes modulated by those DNA sequences. Hence the activation of the p53 gene occurs due to these two processes. These stressors cause various changes in the protein that have the potential to disrupt duplication of the cell that further leads to an increase in mutation rate during cell division. The process that is observed and considered to be related with a mutation in the p53 cell is called gene amplification, deletion and aneuploidy. [34] Malkin et al., [35] concluded that the absence of the p53 gene leads to the development of cancer at an early age.
Functions of P53
P53 is responsible for gene expression that is associated with programmed cell death, formation of the new blood vessels, arrest, and pathways through which DNA repair takes place. Also, its role is seen in the starting of the intrinsic apoptotic pathway leading to the arrest of the cell cycle at G1 phase as an outcome to damage caused to DNA. Apoptosis occurs as a result of the activated cellular signalling cascades by p53 protein when DNA damage occurs. Hence, p53 is crucial for sustaining genomic stability and for governing cell growth and proliferation. [36]
Another important role of P53 is conserving genomic integrity. One of the very common changes in tumors in humans are point mutations of cell proliferation in the p53 gene. The majority of these alterations are missense and often causes loss of formation of protein and production of a mutated protein, which displays an increased half-life. [37, 38] Data from various studies has shown that nuclear p53 protein was recognized during immunohistology staining, and these were related with the existence of p53 gene mutation. It was also reported that the correlation of p53 with certain tumors has been poor and there may not have been a necessary gene alteration, hence this can be useful information for an altered protein function of p53. [17]
Role of P53 in gall bladder cancer
One of the earliest events in the pathogenesis of carcinoma of gallbladder is the mutation of p53 gene. It leads to metaplasia-dysplasia-carcinoma succession of GBC. But the role of p53 in GBCs, as a prognostic marker has not yet been established. [6] Alteration of p53 and the aggregation of p53 were observed in around 27% and 70% of gallbladder carcinomas, respectively. Research in patients with GBCs has demonstrated thatmutations in the middle of axons 5 and 8 correspond to deregulation of the p53 gene. [8]
Many authors have studied the overexpression of p53 concerning GBC. Shu et al. [39] in their study found that expression of p53 is closely related to the progression of carcinoma, p53 expression is closely related to carcinogenesis, progresses rapidly, metastasizes easily, is highly invasive, and has a poor prognosis in GBCs. Kim et al [6] also concluded that overexpression of the gene p53 or its loss is poorly associated with the differentiation of the tumor, showing distant metastases and low specific survival rate. Matsubara et al. [40, 41] found around 75% of p53 gene alterations in GBCs and 16.7% and 35.7% of noncancerous lesions in the common bile duct and gallbladder, respectively. Another study concluded the overexpression of the p53 in the noncancerous lesions of the gall bladder. [42] A study by Nagai et al. [43] also represented similar results where they reported alteration of p53 in GBCs. Wang et al. [44] reported a relative increase of around 59.1% in the expression of p53 in the carcinomas of gall bladder and 17.6% (3/17) of gallbladder adenoma cases (p = 0.009). In a study by Neyaz et al. [45] 103 (44.8%) of the included 230 cases showed mutant protein expression in GBC cases.
Conclusions
There is a wide association of p53 seen in gallbladder carcinomas, which is clear from the literature from past to present. A molecular marker acts above the diagnostic marker in certain suspicious cases, and also it acts as a valuable prognostic tool and can help in providing early intervention to conserve the organ. Not only p53, but there are other markers which can aid in early detection and diagnosing in the development of GBSs hence more research literature is needed in this field.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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