November 2024
Evaluation of ASA, SORT and CACI scores in predicting the need for postoperative intensive care after gynecological malignant surgery
Ahmet Çam, Elzem Sen
Department of Anesthesiology and Reanimation, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
DOI: 10.4328/ACAM.21863 Received: 2024-03-04 Accepted: 2024-05-06 Published Online: 2024-09-28 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):739-742
Corresponding Author: Ahmet Çam, Department of Anesthesiology and Reanimation, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey. E-mail: ahmetcham@hotmail.com P: +90 555 674 57 76 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0571-1883
Other Author ORCID ID: Elzem Sen, https://orcid.org/0000-0003-3001-7324
This study was approved by the Ethics Committee of Gaziantep University (Date: 2020-09-10, No: 2020/225)
Aim: We aimed to investigate the effectiveness of the American Society of Anesthesiologists (ASA), Charlson Age-added Comorbidity Index (CACI) and Surgical Risk Result Tool (SORT) scoring systems in determining postoperative intensive care requirements in patients undergoing gynecological malignancy surgery.
Material and Methods: Our study was carried out retrospectively examining the hospital records of patients who underwent gynecological malignancy surgery. Two groups were formed with the data obtained from the patients’ records in the preoperative and postoperative periods. Group 1: ICU indicated before the surgery and postoperatively ICU follow up needed. Group 2: ICU indicated but postoperatively ICU follow up was not needed. Age, gender, ASA Scoring, smoking, type of surgery, and co-morbid diseases of the patients included in the groups were noted in detail. SORT and CACI scores’ results were recorded by entering patient data electronically.
Results: Age, comorbidity and smoking usage were found to be risk factors in determining the need for postoperative intensive care in patients undergoing general anesthesia. ASA score, SORT score, CACI score were found to be statistically significant in predicting intensive care admission. The efficiency of SORT and CACI was evaluated by ROC analysis and AUC was found to be 0.886 and 0.855, respectively.
Discussion: We think that the CACI and SORT scores can be useful in determining the postoperative ICU need in daily clinical practice.
Keywords: Intensive Care Unit Indication, Charlson Age Comorbidite Index, Surgical Outcome Risk Tool, American Society of Anesthesiologists
Introduction
Surgical treatment is one of the cornerstones of treatment worldwide. Successful perioperative management significantly reduces mortality and morbidity. Being able to accurately determine the need for post-operative intensive care in the preoperative evaluation period in cancer patients can prevent wasting time, which is very valuable in the course of the disease. The operations of patients who need to be arranged in the postoperative intensive care unit (ICU) can be postponed until the ICU location is adjusted [1]. Many factors play a role in the selection of patients who need to be followed in the intensive care unit after surgery. The individual characteristics of the patients, the anesthesia management, and the conditions of the surgical intervention affect the postoperative results [2].
A scoring system that combines factors related to patient, anesthesia and surgery to determine the indication for intensive care has not been developed yet. The ASA (American Society of Anesthesiologists) Score is an evaluation system that is considered useful for determining the anesthesia approach and especially the monitoring methods according to the physical condition of the patient. The Charlson Age Comorbidity Index (aCCI) is a score used to determine comorbidity in surgical or internal problems. The surgical outcome risk tool (SORT) is a score developed for use in estimating mortality for the postoperative 30-day period in adult surgical patients without neurologic disease [3-5].
In this retrospective study; We aimed to investigate the effectiveness of ASA, CACI and SORT scores in determining the need for intensive care in the preoperative evaluation process of patients who underwent gynecological system cancer surgery.
Material and Methods
This retrospective study was conducted by examining the hospital records of patients who had undergone gynecological oncology surgery in our hospital during the 36-month period between 01 July 2017 and 01 July 2020. The data of female patients aged 20-85 years who were operated under elective conditions with the diagnosis of ovarian, endometrium, vulva, vagina and cervix cancer were included in the study. The patients’ data of those who died within 24 hours in the postoperative period, who were evaluated as inoperable by the surgery during the operation and who developed surgical complications such as unpredictable vascular injury or serious organ damage during the operation, who developed life-threatening complications due to anesthesia, and who underwent emergency surgery were excluded from the study. Based on these evaluations, two groups were formed. The number of samples in the groups was determined in line with similar studies.
Group 1: Patients with ICU indication in preoperative evaluation and ICU follow-up after surgery.
Group 2: Patients with an ICU indication in the preoperative evaluation and transferred to the service without the need for post-operative ICU follow-up.
Age, gender, ASA score, smoking, type of surgery and additional diseases (COPD, CAD, CHF, HT and DM) of the patients admitted to the groups were noted in detail.
In our study, the cases; SORT score was entered from http://.sortsurgery.com/ and CACI score calculations were entered electronically from https://www.mdcalc.com/charlson-comorbidity-index-cci#use-cases and the results were recorded.
Statistical Analysis
Analyzes were performed with the help of SPSS 22.0 and MedCalc programs. Student t-test was used to compare numerical variables (age, BMI, preoperative and postoperative Hgb value, case duration) according to groups, and chi-square test was used to compare according to categorical data (co-morbidities, smoking status, ASA score). Receiver operator characteristics curve (ROC) analysis was used while determining the cutoff point for SORT percentage and CACI variables. The area under the ROC curve is between 0.5 and 1.0, and the closer this value is to 1, the better the discriminant power of the test is considered. According to this; area under the curve (AUC) =0.5 no discrimination, 0.5<AUC<0.7 test discrimination power is statistically present but weak, 0.7<AUC<0.8 moderate, 0, 8<AUC<0.9 is considered very good and 0.9<AUC<1 is considered excellent. A significance level of P<0.05 was chosen. By evaluating the data, a cut-off value was tried to be determined for the tests in going to the ICU. A good test should have high sensitivity and specificity. The highest point of both data was determined as the cut-off value.
Ethical Approval
This study was approved by the Ethics Committee of Gaziantep University (Date: 2020-09-10, No: 2020/225).
Results
The mean age of the 96 patients was 61.09±13.21 years (min-max.: 31-84 years), the mean body mass index (BMI) was 26.6±5.33 kg/m2, and the smoking rate was 9.4%.
No significant correlation was found between the BMI, mean duration of the cases, preoperative hemoglobin (Hgb) and postoperative Hgb values and postoperative ICU admissions. However, age, presence of hypertension, presence of coronary artery disease, and smoking increased postoperative ICU admissions in a proportional and statistically significant way (Table 1). Considering the effect of the ASA classification of the patients included in our study on whether or not they were admitted to the ICU, there were 4 different ASA scores in the cases, and only 4 out of 96 patients were determined as ASA I, 23 as ASA II, 68 as ASA III and one as ASA IV. One-way ANOVA test was used for statistical evaluation. Accordingly, as the ASA score increased, it was determined that the percentage of patients hospitalized in the ICU increased. In the data obtained, while there was no admission to the ICU in ASA I physical condition, this rate was 100% in ASA IV. In the statistical evaluation, it was observed that the ASA physical status value had a significant determining effect on ICU admission. In our study, the effect of SORT and CACI indices on determining the need for postoperative ICU was examined by drawing a ROC curve. By determining the sensitivity and specificity of the tests and evaluating the data obtained, it was tried to determine a cut-off value for the tests at admission to the ICU. The AUC-ROC value obtained when evaluating the effect of the SORT test on determining whether the patients would be admitted to the postoperative ICU was found to be 0.886. In addition, it was determined that SORT had the power to determine the need for ICU with 63.4% sensitivity and 100% specificity. The cut-off value for SORT was determined as 1.58%. The AUC-ROC value for the Charlson Comorbidity index with age was determined as 0.855 (Figure 1). It was also found that CACI had 90.2% sensitivity and 65.5% specificity in determining whether patients should be admitted to the ICU. In light of these data, the cut-off value of the CACI index was determined as 4 points (Table 2).
Discussion
In our study, we aimed to evaluate the ASA, SORT and CACI scores and to investigate their effectiveness in predicting the need for postoperative intensive care in patients who had undergone gynecological cancer surgery. Appropriate patient selection for the Intensive Care Unit (ICU) and similar extended postoperative care units is important because of the high cost and limited capacity of the ICU. However, preoperative selection remains difficult due to the large number of high-risk patients and the lack of objective criteria. In the review published by the European Intensive Care Medical Association (ESICM) in 2017, it was evaluated that patient selection for postoperative ICU treatment was the second most important unresolved issue and recommended it as an area to be investigated in the future [6].
Accurate perioperative risk assessment at the individual patient level enables clinical decision making and a clear demonstration of risks when consenting to surgery. Additionally, at the hospital or provider level, adjustment for the patient case mix allows for the evaluation of surgical outcomes or for clinical supervision. A number of risk stratification tools are currently available in clinical practice for both purposes [7,8].
In recent years, many perioperative scoring systems have been described [8]. However, a scoring system that evaluates patient- and surgical-related factors together to preoperatively predict the indication for extended postoperative care has not yet been established. Therefore, the aim of our study is to evaluate the effectiveness of the three scoring systems we used to determine the probability of postoperative ICU admission.
With an effective preoperative risk assessment scoring system, hospitalization in the postoperative intensive care units with the correct indication can be provided and the need for invasive treatment can be reduced. In addition, risky conditions such as circadian rhythm disruption and delirium development can be prevented. Thus, it will be ensured that treatment resources are used effectively for patients who need real ICU hospitalization [9,10].
ASA is the most commonly used preoperative evaluation score by anesthesiologists due to its ease of application and proven clinical data. The relationship between the postoperative condition and the patient’s ASA score and type of surgery has been investigated in many studies [11]. The positive relationship between ASA score and postoperative mortality was first published in the past and was recently emphasized in a large prospective study [12]. In the retrospective cohort studies of Park et al., they observed that the ASA III group showed higher ICU hospitalization rates and prolonged hospital stay compared to the ASA I and II groups [13]. In a study conducted by Gözcü et al., it was concluded that the ASA score was not as significant as CCI in predicting ICU admission rate and length of hospital stay [14]. In our study, it was seen that the ASA score was a successful evaluation score in predicting postoperative ICU exit, in line with previous studies.
CACI is a measure of comorbidity used to standardize the evaluation of surgical patients and has been used in many studies to estimate the postoperative mortality of patients undergoing surgery [15]. So far, CACI has been reported to be a suitable prognostic factor for patients with hepatocellular carcinoma, breast, stomach and colorectal cancer [16-19]. In the study of Klausing et al., it was found that the CCI score is one of the most effective scoring methods for predicting ICU transfer [20]. The CACI score was also evaluated by studies on morbidity and mortality [21]. The number of studies on predicting postoperative intensive care exit is few. In our study, it was evaluated that the CACI score is a strong predictor of admission to the intensive care unit.
In a study conducted by Vahapoglu et al., it was determined that ASA, CACI and SORT were effective in determining the ICU indication during the preoperative evaluation process of patients over 65 years of age undergoing elective surgery. However, the effectiveness of SORT was found to be superior to others. Also it has been shown that SORT can be used before surgery to predict the risk of postoperative morbidity in major elective surgery [7]. Risk stratification tools help clinicians provide more accurate information to patients and guide perioperative care decisions. Simple and cost-effective risk score tools will become increasingly accessible to clinicians for use at the bedside as mobile digital devices become more widely available.
In our study, it was observed that SORT was more powerful than CACI in predicting the admission to the postoperative intensive care unit. SORT is a new system developed for the estimation of mortality in surgical patients. Since it is a system that evaluates the patient’s physical condition and age, as well as surgical status information, and carries almost all the parameters that may cause the need for postoperative ICU, it was thought that it could have a high determinant.
In conclusion; We think that SORT and CACI scoring methods and ASA scoring, which is a traditional preoperative risk assessment tool, have decisive features to predict the need for intensive care in the postoperative period in patients who will undergo gynecological cancer surgery. Prospective multicenter studies can assist in the use, validation and generalization of risk prediction models in daily clinical practice.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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Ahmet Çam, Elzem Sen. Evaluation of ASA, SORT and CACI scores in predicting the need for postoperative intensive care after gynecological malignant surgery.Ann Clin Anal Med 2024;15(11):739-742
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Comparison of the efficacies of crystallized phenol treatment and silver nitrate in the treatment of pilonidal sinus disease
Arslan Hasan Kocamaz 1, Murat Çakır 2, Ömer Kişi 1, Selman Alkan 2, Alper Varman 2, Mustafa Şentürk 2 , Berkan Acar 3, Abdulkadir Çelik 4
1 Department of General Surgery, Aksaray Training And Research Hospital, Aksaray, 2 Department of General Surgery, Faculty of Medicine, Necmettin Erbakan University, Konya, 3 Department of General Surgery, Şebinkarahisar State Hospital, Giresun, 4 Department of General Surgery, Uzunköprü State Hospital, Edirne, Turkey
DOI: 10.4328/ACAM.22144 Received: 2024-02-12 Accepted: 2024-05-13 Published Online: 2024-08-24 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):743-747
Corresponding Author: Alper Varman, Department of General Surgery, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey. E-mail: avarman@erbakan.edu.tr P: +90 554 818 23 34 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1918-5143
Other Authors ORCID ID: Arslan Hasan Kocamaz, https://orcid.org/0000-0002-5257-9611 . Murat Çakır, https://orcid.org/0000-0001-8789-8199 . Ömer Kişi, https://orcid.org/0000-0001-8606-2453 . Selman Alkan, https://orcid.org/0000-0003-2974-7610 . Mustafa Şentürk, https://orcid.org/0000-0002-3230-1743 . Berkan Acar, https://orcid.org/0000-0001-9798-295X . Abdulkadir Çelik, https://orcid.org/0000-0002-5537-7791
This study was approved by the Ethics Committee of Necmettin Erbakan University (Date: 2020-12-18, No: 2951)
Aim: Pilonidal sinus is a disease localized in the sacrococcygeal region that mostly affects young adults and men and can be treated with conservative treatment methods. In this context, the objective of this study is to compare the efficacies of crystallized phenol and silver nitrate applications, two of the conservative treatment methods used in the treatment of pilonidal sinus disease.
Material and Methods: The sample of this retrospective clinical study consisted of 90 patients diagnosed with pilonidal sinus disease and treated nonoperatively.
Results: The primary complaints of the patients were discharge, pain and swelling. The mean age of the patients treated with crystallized phenol and silver nitrate was 22.5 (±7.5) and 25 (±7.5) years, respectively. Of the 90 patients, 42 (46.7%) had 2 sinus cavities, 18 (20%) had 3, 17 (18.9%) had 1, and 13 (14%) had 4. The number of times the treatment procedure was repeated was significantly higher in the silver nitrate group than in the crystallized phenol group [(2.95 (±1.3) vs. 2.22 (±0.82)].
Discussion: In conclusion, the silver nitrate treatment is an alternative treatment method to the crystallized phenol treatment or may even be the ideal treatment method in the treatment of pilonidal sinus.
Keywords: Pilonidal Sinüs, Silver Nitrate, Phenol
Introduction
Pilonidal sinus disease is a symptom complex that is frequently localized in the sacrococcygeal region and affects young adults more, leading to cyst and abscess formation from the skin depression or sinus formation as a result of the chronic infection. Many theories featuring congenital and acquired causes have come to the fore in the etiology of the pilonidal sinus disease. Today, the theory featuring acquired causes is more prominent in the development of pilonidal sinus disease [1, 2]. Pilonidal sinus is observed 6 to 7 times more frequently in men compared to women [3].
Many surgical and conservative methods have been used to date in the treatment of pilonidal sinus disease. However, some of the surgical treatment methods cause more postoperative problems than the problems caused by the pilonidal sinus disease, that is, the morbidity of the surgery can take precedence over the morbidity of the disease itself [4]. The ideal treatment for pilonidal sinus disease should be a simple method with less recurrence rate, complications, pain, and need for wound care, short hospitalization time, and low treatment cost which allows returning to normal life in a short time. Nevertheless, there is still no consensus about an ideal treatment method that meets these criteria.
One of the most common conservative treatment methods used in the treatment of pilonidal sinus involves the application of crystallized phenol, the efficacy of which has been proven by many studies. The main purpose of applying crystallized phenol is to irritate the sinus cavity with phenol, a sclerosing substance, and fill it with granulation tissue. Nonetheless, this treatment method is reportedly associated with recurrence rates of 18.6% [5].
Another conservative treatment method used in the treatment of pilonidal sinus involves the application of silver nitrate, a lytic agent that is widely used in dressings and wound care products aimed at the treatment of difficult wounds [6, 7]. It has been demonstrated that silver nitrate causes epithelial cell destruction and accelerates wound healing by eliminating excess granulation tissue that activates fibroblasts in various clinical conditions such as perianal fistula and sinus [8].
In view of the foregoing, the objective of this study is to compare the efficacies of crystallized phenol and silver nitrate applications, two of the conservative treatment methods used in the treatment of pilonidal sinus disease.
Material and Methods
This retrospective clinical study study was carried out in Necmettin Erbakan University Meram Medical Faculty Hospital General Surgery Clinic. All patients were informed in detail about the procedure to be performed. The consent form was obtained from all patients.
The study’s population included cases who were diagnosed with pilonidal sinus disease and received nonoperative treatment at the General Surgery Polyclinics of Meram Medical Faculty Hospital between February 2017 and May 2021. Patients younger than 18 and older than 65, patients who smoke, have chronic diseases (e.g., diabetes and chronic obstructive pulmonary disease (COPD), etc.) were not included in the study. In the end, the study sample consisted of 90 patients. Patients’ demographic characteristics, including age and gender, clinical characteristics including their pilonidal sinus disease-related complaints, duration of the pilonidal sinus disease, the number of sinus cavities they had, the number of procedures they received, and whether complications developed after the procedure were recorded. Patients were randomly assigned to crystallized phenol or silver nitrate treatment groups according to the date when they were first admitted to the hospital. The treatment processes and the number of procedures administered to the patients participating in the study were recorded in detail.
Crystallized Phenol Treatment
The patients were advised to clean the hair in the sacrococcygeal region the day before the procedure. Crystallized phenol was applied while the patients were in prone position under local anesthesia in the intervention room. The sinus orifice was widened with the help of a clamp, and the hairs and debris were removed (Figures 1&2). The skin around the external opening of the sinus was protected with 0.2% nitrofurazone ointment. Phenol crystals were placed into the sinus with the help of a clamp from the widened orifice, filling the cavity completely. After they were kept in the sinus for 1-3 minutes, the sinus contents were cleaned again and curetted. The dressing was closed and the procedure was completed. After the procedure, the patients were sent home with the recommendation to continue hair removal in the sacrococcygeal region and come to the hospital for a follow-up visit in three weeks.
Silver Nitrate Treatment
As with the crystallized phenol treatment, local anesthesia was applied to the area to be treated after the sacrococcygeal hair was cleaned. The sinus orifice, which the silver nitrate stick could not reach, was widened with the help of a clamp and the hairs and debris were removed (Figures 1&2). The same procedure was repeated for each patient with more than one sinus orifice. The skin was protected with 0.2% nitrofurazone ointment to prevent the irritating effects of the silver nitrate stick. A silver nitrate stick was placed in the widened orifice. A separate stick was used for each sinus cavity in patients with more than one sinus cavity. The silver nitrate stick was left inside for 1-2 minutes. Afterwards, the necrotic tissue and hairs formed in the orifice were cleaned and covered with a dressing and the procedure was completed. After the procedure, the patients were sent home with the recommendation to continue hair removal in the sacrococcygeal region, come to the hospital for a follow-up visit in three weeks, and not to take a bath in the first 24 hours after the procedure.
Follow-up
Patients who received crystallized phenol and silver nitrate treatments were called to the hospital for follow-up visits at 3-week intervals after the procedure. In the control examinations, patients were asked about whether their complaints regressed. In the physical examination, whether patients’ condition improved was evaluated and the result of this evaluation was recorded. The treatment was terminated in patients who recovered and they were asked to come to the hospital for a follow-up visit in 6 months. The patients whose overall complaints regressed but discharge and consequent maceration around the sinus persisted, and patients with no granulation in the sinus were considered to have insufficient recovery. The procedure was repeated in patients with insufficient recovery or no recovery. After the procedure, the patients were called for follow-up visits at 3-week intervals.
Failure to detect improvement during the control examinations performed at the one-year follow-up visits in both treatment groups was considered as “treatment failure”. Disappearance of complaints, complete closure of the sinus cavity, and absence of discharge were considered as complete recovery. Recurrence of symptoms and detection of sinus formation on physical examination after complete recovery was considered as “relapse”.
Ethical Approval
This study was approved by the Ethics Committee of Necmettin Erbakan University (Date: 2020-12-18, No: 2951).
Results
A total of 90 patients, 75 (83.3%) male and 15 (16.7%) female, were included in the study. Of these patients, 50 were treated with crystallized phenol and 40 with silver nitrate. The mean age of the patients treated with crystallized phenol and silver nitrate was 22.5 (±7.5) and 25 (±7.5) years, respectively. There was no statistically significant difference between the groups in terms of age (p=0.096). Of the male patients, 39 (52%) were treated with crystallized phenol and 36 (48%) with silver nitrate, and of the female patients, 11 (73%) were treated with crystallized phenol and 4 (26.7%) with silver nitrate. There was no significant difference between the groups in terms of gender (p=0.129) (Table 1). Thirty-four (37.8%) patients had discharge complaints, and 30 (33.3%) patients had both discharge and pain complaints. There was no significant difference between the groups in terms of the rates of patients with complaints (p=0.173)
As for the duration of disease-related complaints, it was determined that 27 (30%) patients had complaints for 12 to 24 months, and 22 (24.4%) patients had complaints for more than 24 months (Table 1).
In terms of the number of sinuses, 42 (46.7%) had 2 sinus cavities, 18 (20%) had 3, 17 (18.9%) had 1, and 13 (14%) had 4. There was no statistically significant difference between the groups in the number of sinus cavities (p=0.275) (Table 1).
Within the scope of the control examinations performed during the one-year follow-up visits, it was determined that 46 (92%) patients in the crystallized phenol group recovered, whereas 2 (4%) did not recover, and 2 (4%) relapsed, and that 38 (95%) patients in the silver nitrate group recovered, 1 (2.5%) did not recover, 1 (2.5%) relapsed. There was no statistically significant difference between the groups in terms of patients’ recovery rates determined during the one-year follow-up visits (p=0.355) (Table 2).
The number of the treatment procedure that was repeated in the crystallized phenol and silver nitrate groups is shown in Table 3. The mean number of procedures applied was 2.22 (±0.82) in the crystallized phenol group and 2.95 (±1.3) in the silver nitrate group. The number the treatment procedure was repeated was significantly higher in the silver nitrate group than in the crystallized phenol group (p=0.003) (Table 3). Post-procedure hematoma, seroma, and wound infection did not develop in any of the patients in either group. None of the patients required any additional anesthesia other than local anesthesia. Bed rest was not recommended to any of the patients and no movement restriction was imposed.
Discussion
There has been much debate over whether pilonidal sinus disease is congenital or acquired. However, the general opinion today is that the disease is acquired [2]. In parallel, the patient’s anamneses taken within the scope of this study, the age of onset and the type of the disease-related complaints suggest that pilonidal sinus disease is acquired.
Pilonidal sinus disease is observed 6 to 7 times more frequently in men compared to women [3]. The incidence of the disease is reportedly higher in the 17-27 age group. In the literature, the mean age of onset of symptoms and the mean age of admission to hospital has been reported as 21 and 25, respectively [9]. In line with the literature, 75 of the 90 patients included in this study were male and 15 were female, indicating a 5:1 male/female ratio, and the mean age of onset of symptoms was 23.6 years.
In the literature, the success rate of crystallized phenol treatment varies between 70-95%, no complications were reported, and the recurrence rate was reported as 4.9% [10-12]. It has been shown that in the presence of an abscess, the first drainage of the abscess reduces recurrence [13]. Similarly, in this study, the success rate of crystallized phenol treatment was 92%, no complications were observed, and the recurrence rate was 4%.
Studies have reported that the success rate increases with the repetition of crystallized phenol treatment (52-53). In parallel, in this study, the success rate increased with the repetition of the crystallized phenol treatment. Accordingly, 11 (22%) patients recovered with one course of treatment, 18 (36%) with 2 courses of treatment, and 21 (42%) with 3 courses of treatment. Thus, patients received an average of 2.22 courses of treatment.
In a study involving 587 patients, the mean number of orifices in physical examination was reported as 2.71 (min.1, max. 9) [14]. In comparison, the mean number of orifices was calculated as 2.3 (min. 1, max. 4) in this study.
There are studies on nonoperative treatment of pilonidal sinus disease with different substances other than phenol. In a study including 400 cases, surgical treatment was compared with local Lawsonia inermis (henna) application and it was found to be quite successful in terms of both disease recurrence and return to work time [15]. There are not many studies in the literature on the use of silver nitrate in the treatment of pilonidal sinus. Studies on the clinical use of silver nitrate seem to be insufficient. In this study, the success rate of silver nitrate treatment was found to be 95%. No complications were observed, and the recurrence rate was 2.5%. There was no statistically significant difference between the crystallized phenol and silver nitrate treatment groups in terms of patients’ recovery rates determined during the one-year follow-up visits (p=0.355).
Doğru et al. [10] followed up the patients to whom they applied crystallized phenol for 24 months, and Ölmez et al. [11] followed up for 25 months. In comparison, the follow-up period in this study was one year, which was not sufficient to identify all relapsed patients. This relatively shorter follow-up period was the primary limitation of this study. Longer-term prospective randomized studies are needed to reach a conclusion about recurrence rates.
The use of silver nitrate in the treatment of pilonidal sinus has significant advantages, such as the fact that it can be applied to outpatients, does not require hospitalization, and enables full recovery early. In addition, it is a simple and straightforward method, associated with less pain, less need for wound care, and low treatment cost and allows returning to normal life in a short time.
The findings of this study demonstrated that the efficacy of silver nitrate treatment, which is a novel treatment method, is comparable to the generally accepted crystallized phenol treatment, the efficacy of which was established in the literature. Moreover, the silver nitrate treatment offers certain advantages over the crystallized phenol treatment as it causes less damage to healthy tissue, and is easier to apply and store.
Limitation
The small number of patients included in the study and the short follow-up period after the procedure are limitations of our study. Additionally, our study is single-centered. A multicenter study that includes a high number of cases and continues for a long follow-up period may provide more definitive findings on the subject.
Conclusion
Silver nitrate treatment is an alternative treatment method to crystallized phenol treatment, and it has even been concluded that it may be the ideal treatment method for the treatment of pilonidal sinus.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Brandt CP, Malangoni MA, Priebe PP, Temes TT. Shackelford’s surgery of the alimentary tract, 5th edition. Ann Surg. 2002;236(2):261.
2. Okus A, Sevinc B, Aksoy N, Eryılmaz MA, Karahan Ö, Bodur S, et al. Prevelance of pilonidal disease in society, by age and sex distrubution (early results). Selçuk Tıp Derg. 2013;29(3):120-122.
3. Bender O. Pilonidal sinüs tedavisinde Limberg flep [Limberg Flap in the treatment of pilonidal sinus.] Cerrahi Tıp Bülteni. 1993(2):17-20.
4. Senapati A, Cripps NPJ. Bascom’s operation in the day-surgical management of symptomatic pilonidal sinus. Br J Surg. 2000;87(8):1067-1070.
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6. Oliveira RN, Rouzé R, Quilty B, Alves GG, Soares GD, Thiré RM, et al. Mechanical properties and in vitro characterization of polyvinyl alcohol-nano-silver hydrogel wound dressings. Interface Focus. 2014;4(1):20130049.
7. Mulley G, Jenkins AT, Waterfield. Inactivation of the antibacterial and cytotoxic properties of silver ions by biologically relevant compounds. NR.PLoS One. 2014;9(4):e94409.
8. Attaallah W, Tuney D, Gulluoglu BM, Ugurlu MU, Gunal O, Yegen C. Should we consider topical silver nitrate irrigation as a definitive nonsurgical treatment for perianal fistula?. Dis Colon Rectum. 2014;57(7):882-887.
9. Brearyl R. Pilonidal Sinus: A new theory of origin. Br J Surg. 1955;43:62-67.
10. Dogru O, Camcı C, Aygen E, Girgin M, Topuz O. Pilonidal sinus treated with crystallized phenol: An eight-year experience. Dis Colon Rectum. 2004;47:1934-1938.
11. Ölmez A, Kayaalp C, Aydın C. Treatment of Pilonidal disease by combination of pit excision and phenol application. Tech Coloproctol. 2013;17:201-206.
12. Kayaalp C, Aydin C. Review of phenol treatment in sacrococcygeal pilonidal disease. Tech Coloproctol. 2009;13:189‐193.
13. Doll D, Matevossian E, Hoenemann C, Hoffmann S. Incision and drainage preceding definite surgery achieves lower 20‐year long‐term recurrence rate in 583 primary pilonidal sinus surgery patients. J Dtsch Dermatol Ges. 2013;11(1):60‐64.
14. Harlak A, Menteş Ö, Özer M, Ersöz N,Coşkun A. Evaluation of history and physical examination data of 587 patients with sacrococsigeal pilonidal disease. Eurasian J Med. 2006;38:103-106.
15. Salih AM, Kakamad FH, Salih RQ, Mohammed SH, Habibullah IJ, Hammood ZD, et al. Nonoperative management of pilonidal sinus disease: one more step toward the ideal management therapy-a randomized controlled trial. Surgery, 2018;164(1):66-70.
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Arslan Hasan Kocamaz, Murat Çakır, Ömer Kişi, Selman Alkan, Alper Varman, Mustafa Şentürk, Berkan Acar, Abdulkadir Çelik. Comparison of the efficacies of crystallized phenol treatment and silver nitrate in the treatment of pilonidal sinus disease. Ann Clin Anal Med 2024;15(11):743-747
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Our five-year clinical experience of colorectal tumors located in the transverse colon
Uğur Topal 1, Ahmet Onur Demirel 1, Burak Yavuz 1, İshak Aydın 2, Orçun Yalav 3, İsmail Cem Eray 1
1 Department of General Surgery, Faculty of Medicine, Cukurova University, 2 Department of Surgical Oncology, Faculty of Medicine, Cukurova University, 3 Department of General Surgery, Acibadem Adana Hospital, Adana, Turkey
DOI: 10.4328/ACAM.22179 Received: 2024-03-14 Accepted: 2024-05-06 Published Online: 2024-08-15 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):748-752
Corresponding Author: Uğur Topal, Department of General Surgery, Faculty of Medicine, Cukurova University, Adana, Turkey. E-mail: sutopal2005@hotmail.com P: +90 322 338 60 60 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1305-2056
Other Authors ORCID ID: Ahmet Onur Demirel, https://orcid.org/0000-0002-0313-5467 . Burak Yavuz, https://orcid.org/0000-0002-5262-0346 . İshak Aydın, https://orcid.org/0000-0002-6366-2461 . Orçun Yalav, https://orcid.org/0000-0001-9239-4163 . İsmail Cem Eray, https://orcid.org/0000-0002-1560-7740
This study was approved by the Ethics Committee of Cukurova University (Date: 2023-11-03, No: 138/28)
Aim: Treating transverse colon cancer surgically can involve either extended colectomy or segmental resection, depending on tumor location and surgeon preference. This study explores our tertiary care center’s surgical approaches to transverse colon cancer.
Material and Methods: We analyzed patients with transverse colon adenocarcinoma who underwent curative transverse or segmental colectomy (2016-2021). Data included demographics, clinical presentation, surgical details, lymph node dissection, pathology, post-op outcomes, and survival.
Results: This research included 15 patients (5 transverse colectomy, 10 extended hemicolectomy). Demographics were similar between groups. Minimally invasive surgery rates were 20% (transverse colectomy) and 40% (extended hemicolectomy). Operation time, anastomotic technique, and hospital stay didn’t significantly differ. Surgical site infection was the most common complication for both groups. Extended hemicolectomy yielded more dissected lymph nodes (p=0.028), but malignant lymph node count was similar. Pathology stages were not statistically different between groups, and average survival times were comparable.
Discussion: Our study suggests similar postoperative outcomes for transverse colectomy and extended colectomy in transverse colon cancer. While extended colectomy yielded more lymph nodes, this didn’t significantly impact long-term survival. With careful patient selection, both techniques appear safe and feasible, despite the limited patient numbers in our study.
Keywords: Colon Cancer, Transverse Colon, Adenocarcinoma, Prognosis
Introduction
In 2018, global estimates projected over 1.8 million new cases of colorectal cancer (CRC) and 881,000 resultant deaths, positioning CRC as the third most commonly diagnosed cancer, contributing to 10.2% of cases, and the second leading cause of cancer mortality, responsible for 9.2% of such deaths [1]. Transverse colon cancer (TCC) is characterized in scholarly texts as tumors situated between the hepatic and splenic flexures, constituting a relatively infrequent occurrence, representing about 10% of colorectal cancers [2]. The transverse colon, embryologically derived from two-thirds midgut and one-third hindgut, shares certain features with right colon cancer (RCC) and others with left colon cancer (LCC). The intricate anatomy and embryology of the transverse colon render its mobilization and resection a procedurally challenging task [3, 4].
The surgical treatment of TCC is subject to ongoing discourse. Surgical intervention remains a pivotal element in colon tumor management. Both transverse colectomy and extended hemicolectomy are viable options for TCC. The definitive best surgical approach for TCC, however, has yet to be established. The decision between these two approaches largely hinges on the surgeon’s discretion and experience, in the absence of consistent comparative data. A key point of contention in this debate is whether segmental colectomies or extended hemicolectomies offer superior outcomes in terms of higher lymph node yield, increased separation between the tumor and central vasculature, and, as a result, improved disease-free survival (DFS) via a more comprehensive mesocolic excision [5-8].
In summary, these factors contribute to the complexity of standardizing transverse colon surgery and often lead to the exclusion of this patient group from numerous randomized controlled trials [9-11]. In our retrospective series at a tertiary center, we examined the optimal surgical approach for TCC by comparing outcomes between extended hemicolectomy and transverse colectomy.
Material and Methods
This study encompassed patients diagnosed with adenocarcinoma, who underwent segmental transverse colectomy or extended hemicolectomy as curative surgical treatment, with the primary tumor focus in the transverse colon, during the period from 2016 to 2021. Excluded from the study were individuals under the age of 18, patients with non-adenocarcinoma pathology, those who underwent subtotal colectomy or total proctocolectomy, and cases with incomplete follow-up data. Patient data were collected from clinical follow-up records, postoperative tracking forms, and pathology reports.
Analyzed data included demographic information, presenting symptoms, preoperative levels of hemoglobin (HGB in g/dL), albumin (g/dL), tumor marker levels, American Society of Anesthesiologists (ASA) score, history of abdominal surgery, details of the surgical technique employed, number of dissected lymph nodes, pathological stage, postoperative outcomes, and current clinical status.
Tumor staging was conducted using the American Joint Committee on Cancer (seventh edition) staging system. All patients with colon cancer underwent CT or colonoscopy prior to surgery for tumor localization. If radiological localization was unclear, preoperative colonoscopy was performed for marking.
Preoperative preparation included mechanical bowel preparation and oral antibiotic therapy. Intravenous antibiotics were administered during surgery and continued for 48 hours postoperatively. The surgical procedure for transverse colon cancer was selected based on the tumor’s location. Extended colectomies encompassed both extended right and left hemicolectomies. Tumors located at the hepatic flexure or within 10 cm distally were treated with extended right hemicolectomy, while those at the splenic flexure or within 10 cm proximally were treated with extended left hemicolectomy. Tumors situated between these two locations were addressed with transverse colectomy. Extended right hemicolectomy was defined as a mesocolic excision with ligation at the origin of the ileocolic, right colic, and middle colic vessels; extended left hemicolectomy was similarly defined, involving ligation at the origins of the left colic and middle colic vessels. Transverse colectomy entailed lymphadenectomy with ligation at the origins of the middle colic vessels. The choice of laparoscopic surgical technique was based on individual preference.
Indications for adjuvant chemotherapy and chemotherapy regimens were based on the National Comprehensive Cancer Network (NCCN) guidelines. Postoperative follow-ups were routinely conducted at our clinic, initially every 3 months for the first 2 years, then every 6 months for the next 3 years, and subsequently once a year for 5 years.
Statistical Analysis
The collected numerical data from patients who underwent surgery for colon cancer were initially assessed for normal distribution adherence using the Shapiro-Wilk test. For data not conforming to normal distribution, the Mann-Whitney U test was employed for bi-group comparisons in non-parametric analysis. Conversely, for data adhering to normal distribution, the Independent t-test was utilized.
Categorical variables were analyzed using the Chi-square test. A significance level was set at p<0.05. Survival analysis was conducted using the Kaplan-Meier method. Furthermore, the Cox regression model was applied to evaluate the survival function of continuous variables. This model was also used for both univariate and multivariate analyses to identify factors influencing survival. Additionally, linear regression analysis was employed to ascertain the impact of independent variables on the continuous dependent variable.
Ethical Approval
This study was approved by the Ethics Committee of Cukurova University (Date: 2023-11-03, No: 138/28).
Results
Our study included 15 patients, divided into two groups: Group 1 consisted of 5 patients who underwent transverse colectomy, and Group 2 comprised 10 patients who underwent extended hemicolectomy. Of these, 7 were female, with an average age of 65.8 years and a mean Body Mass Index (BMI) of 27.67. The median preoperative CEA level was 4.6 (range 0-1438). The most common presenting symptom was abdominal pain (60%), and the most frequent ASA score was ASA2 (53%). The demographic and clinical data are presented in Table 1.
The history of previous abdominal surgery was similar across the groups (p=0.264). The rate of minimally invasive surgery was 20% in Group 1 and 40% in Group 2. The duration of the operation and the technique of anastomosis were comparable across the groups (p>0.05), as shown in Table 2.
In the postoperative period, the length of hospital stay was not related to the type of operation or technique used in either group. The most common complication in both groups was surgical site infection (60% in Group 1 vs 40% in Group 2, p=0.990). The average number of dissected lymph nodes was higher in Group 2 (13 vs. 19.5, p=0.028), but the number of malignant lymph nodes was similar. The distribution of pathological stages was also similar across the groups (p=0.049), as demonstrated in Table 3.
Survival times were, Group 1 Mean+std 55.08+14.87 95%CI (25.93-84.23) Group 2 Mean+std 91.9+8.72 95%CI (65.48-101.32) (p=0.219), with the survival rates depicted in 4 and Figure 1.
Discussion
In this study presenting surgical outcomes in transverse colon cancer, we found similar postoperative complication rates between transverse colectomy and extended colectomies. As anticipated, the number of dissected lymph nodes was higher in the extended colectomy group, yet no significant difference was observed in long-term survival rates.
Distinct from right and left colon cancers, transverse colon cancer necessitates various surgical approaches based on localization. These include subtotal colectomy, extended right or left hemicolectomy, right or left hemicolectomy, transverse colectomy, and segmental resection such as splenic flexure colectomy. Two main issues pertain to the surgical approach to transverse colon cancer: the extent of resection and the minimally invasive approach [11].
Morarasu et al., in their meta-analysis comparing the outcomes of extended and segmental resections, involved a total of 3995 patients. Their analysis revealed that segmental resection offered better outcomes in terms of operation duration and postoperative ileus. Conversely, extended resection had advantages in terms of anastomotic leak and the number of dissected lymph nodes. They demonstrated that hospital stay duration, disease recurrence, and overall survival were similar between the two procedures [12]. Contrarily, a study utilizing the United States National Cancer Database found that extended surgery resulted in poorer survival, specifically indicating that extended operations in the mid transverse colon led to worse long-term outcomes. This study suggested that extended colectomy did not confer a survival advantage over segmental resection [13]. Our study, diverging from the literature, showed similar postoperative complications for both surgical techniques, which could be attributed to the limited number of patients. We found no differences in survival, which we associate with adequate lymph node dissection and proper management in the postoperative period.
Literature has demonstrated that, in colon cancer surgery, the laparoscopic technique offers significant benefits over open surgery, including shorter hospital stays, reduced postoperative pain, and similar oncological outcomes with a quicker return to normal activities. However, it’s noteworthy that patients with transverse colon tumors are often excluded from these randomized studies [14, 15]. In their meta-analysis, Athanasiou et al. examined the outcomes of the laparoscopic approach in transverse colon cancer. Their study indicated that the laparoscopic approach maintains crucial advantages seen in right and left colectomy techniques, such as shorter hospital stays and equivalent times to transition to an oral diet, as well as comparable overall and disease-free survival. These benefits continued in the extended lymphadenectomy group. They also found equivalent rates of local recurrence and development of metastatic disease between the two groups [16]. In our series, a third of the patients underwent a laparoscopic approach. We found the operation duration to be similar across both techniques, which we attribute to the completion of our institutional learning curve. The choice of surgical approach was not influenced by the type of operation.
Limitation
The limitations of our study include a limited number of patients and its retrospective nature. In our single-center study, individual decisions also influenced the choice of surgical technique.
Conclusion
Transverse colon cancer is a technically challenging and relatively rare malignancy to resect. The surgical management of transverse colon cancer necessitates personalized approaches, taking into account the surgeon’s skills, patient anatomy, and tumor status. Although our study found similar postoperative and oncological outcomes between the two surgical techniques, multicenter prospective randomized studies are needed to elucidate the comparative advantages of surgical techniques in transverse colon cancer. Both surgical techniques can be safely applied in transverse colon cancer. Adhering to oncological principles such as adequate margins and sufficient lymph node harvest appears to be more critical than the choice of the surgical approach itself, which should be selected based on the surgeon’s preference and proficiency in each 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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
2. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): Analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023-75.
3. Li C, Wang Q, Jiang KW. What is the best surgical procedure of transverse colon cancer? An evidence map and minireview. World J Gastrointest Oncol. 2021;13(5):391-9.
4. Leijssen LGJ, Dinaux AM, Amri R, Kunitake H, Bordeianou LG, Berger DL. A transverse colectomy is as safe as an extended right or left colectomy for mid-transverse colon cancer. World J Surg. 2018;42(10):3381-8.
5. Milone M, Manigrasso M, Elmore U, Maione F, Gennarelli N, Rondelli F, et al. Short- and long-term outcomes after transverse versus extended colectomy for transverse colon cancer: A systematic review and meta-analysis. Int J Colorectal Dis. 2019;34(2):201-207.
6. Chong CS, Huh JW, Oh BY, Park YA, Cho YB, Yun SH, et al. Operative method for transverse colon carcinoma: Transverse colectomy versus extended colectomy. Dis Colon Rectum. 2016;59(6):630-9.
7. Martínez-Pérez A, Reitano E, Gavriilidis P, Genova P, Moroni P, Memeo R, et al. What is the best surgical option for the resection of transverse colon cancer. Ann Laparosc Endosc Surg. 2019;4(0):69.
8. Nelson H, Sargent DJ, Wieand HS, Fleshman J, Anvari M, Stryker SJ, et al. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med. 2004;350(20):2050-9.
9. Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM, et al. MRC CLASICC trial group. Short-term endpoints of conventional vs laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): Multicentre, randomised controlled trial. Lancet. 2005;365(9472):1718-1726.
10. Colon Cancer Laparoscopic or Open Resection Study Group, Buunen M, Veldkamp R, Hop WC, Kuhry E, Jeekel J, et al. Survival after laparoscopic surgery vs open surgery for colon cancer: Long-term outcome of a randomised clinical trial. Lancet Oncol. 2009;10(1):44-52.
11. Kim HJ, Park JW. Surgical outcomes of various surgical approaches for transverse colon cancer. J Minim Invasive Surg. 2022;25(1):1-11.
12. Morarasu S, Clancy C, Cronin CT, Matsuda T, Heneghan HM, Winter DC. Segmental versus extended colectomy for tumours of the transverse colon: A systematic review and meta-analysis. Colorectal Dis. 2021;23(3):625-36.
13. Crippa J, Grass F, Achilli P, Behm KT, Mathis KL, Day CN, et al. Surgical approach to transverse colon cancer: Analysis of current practice and oncological outcomes using the National Cancer Database. Dis Colon Rectum. 2021;64(3):284-92.
14. Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM, et al. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): Multicentre, randomised controlled trial. Lancet. 2005;365(9472):1718-26.
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16. Athanasiou CD, Robinson J, Yiasemidou M, Lockwood S, Markides GA. Laparoscopic vs open approach for transverse colon cancer: A systematic review and meta-analysis of short and long term outcomes. Int J Surg. 2017;41:78-85.
Download attachments: 10.4328.ACAM.22179.pdf
Uğur Topal, Ahmet Onur Demirel, Burak Yavuz, İshak Aydın, Orçun Yalav, İsmail Cem Eray. Our five-year clinical experience of colorectal tumors located in the transverse colon. Ann Clin Anal Med 2024;15(11):748-752
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Overview of clinical anatomy of the sciatic nerve: Re-evaluation with a cadaveric study
Alperen Doguhan Oguz, Ismihan Ilknur Uysal, Betul Digilli Ayas, Ahmet Safa Goksan
Department of Anatomy, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.22184 Received: 2024-03-20 Accepted: 2024-05-06 Published Online: 2024-08-24 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):753-758
Corresponding Author: Ismihan Ilknur Uysal, Department of Anatomy, Faculty of Medicine, Necmettin Erbakan University, 42090, Konya, Turkey. E-mail: uysali@yahoo.com P: +90 542 317 17 45 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2939-9767
Other Authors ORCID ID: Alperen Doguhan Oguz, https://orcid.org/0000-0001-6196-9294 . Betul Digilli Ayas, https://orcid.org/0000-0002-5150-5987 . Ahmet Safa Goksan, https://orcid.org/0000-0001-9352-875X
This study was approved by the Ethics Committee of Necmettin Erbakan University Non-Pharmaceutical and Non-Medical Device Research (Date: 2021-02-05, No: 2021/3091)
Aim: This study focused on determining the exit variations and branching pattern of the sciatic nerve (SN), obtaining morphometric data of the lower extremity and correlating these data with nerve blockade procedures.
Material and Methods: The lower extremities of twenty human cadavers were prospectively dissected, and the distances between superficial and deep reference points, the thickness of the SN and its branches were measured. The exit of the SN to the gluteal region, its course at the back of the thigh, and its terminal branching level were examined.
Results: The literature review determined that at least 5 and at most 13 different sciatic nerve types were defined according to their relationship with the piriformis. During the dissections, it was observed that 95% of the SN passed under the piriformis as a single root and bifurcated in all lower extremities. The bifurcation level of the SN in the upper, middle and lower thighs was close to each other (35%, 35%, 30%, respectively). Statistically significant (p<0.05) correlations were detected between distances using the greater trochanter as a reference and thigh length.
Discussion: The obtained correlations support the use of the greater trochanter in determining the point of trans-gluteal SN blockade. If sciatic nerve blockade in the thigh cannot be performed with imaging methods, performing it at the level above the popliteal fossa as much as possible, considering the person’s thigh length, will increase success.
Keywords: Sciatic Nerve, Variations, Piriformis, Nerve Blocking
Introduction
The sciatic nerve (SN), a continuation of the sacral plexus, is the body’s thickest and longest peripheral nerve. The SN, whose initial part is located in the pelvis, leaves the pelvis through the infrapiriform foramen and exits to the gluteal region. It usually extends from the lower border of the piriformis in the gluteal region to the upper level of the popliteal fossa, where it bifurcates into its terminal branches (tibial and common peroneal nerves). A common sheath surrounds it up to the bifurcation (BFR), while the tibial nerve (TN) and common peroneal nerve (CPN) are surrounded by different sheaths [1-3]. Many studies have investigated the relationship between SN and piriformis, and some have classified this relationship [3, 4-9].
The incidence of damage to the SN is high due to its thickness and long course. In addition, piriformis syndrome, intervertebral disc, hip joint and pelvis pathologies, gluteal intramuscular injection, nerve inflammation, or pressure during labor may cause sciatica, motor and sensory loss. Although variations in the SN and its branches, other than those related to the piriformis, do not cause symptoms, undesirable results may occur in interventions in this region [6, 8, 10].
This study, which includes a literature review on SN anatomy, aims to contribute to nerve blockade applications by additionally performing gluteal and posterior thigh dissections.
Material and Methods
The study was performed prospectively in the Anatomy Laboratory on 20 lower extremities of 10 adult human cadavers, aged between 40 and 80 years, fixed with 10% formalin. Variations and nerve branching were recorded with a digital camera and schematized. The same person repeated the length and distance measurements three times using a tape measure and the thickness measurements using a caliper.
Measurements and dissections were made in the prone position. Before dissection, palpable bone formations were marked as reference points. Then, thigh length (distance between the greater trochanter and lateral condyle of femur, TL), lower extremity length (distance between anterior superior iliac spine and medial malleolus, LEL), the distance between the greater trochanter and the posterior superior iliac spine (GT-PSIS), and the distance between the greater trochanter and the sacral hiatus (GT-SH) were measured. The superficial GT-SH distance was marked by dividing it into three parts (medial, middle and lateral) to determine the position of the dissected SN. The point where the line drawn perpendicularly from the midpoint of GT-PSIS intersects with GT-SH was defined as the superficial blocking point of SN [11].
Following superficial measurements, gluteus maximus, connective and fatty tissue dissection was performed and piriformis and SN were exposed. Hamstring muscles and later parts of SN at the back of the thigh were dissected. The passage of the SN to the subgluteal region was evaluated according to the relationship of the nerve with the piriformis [1-3-5]. The branching pattern (bifurcation, trifurcation, etc.) and level (distal 1/3, middle 1/3, proximal 1/3) of the SN were determined. The connecting branches between TN and CPN were evaluated according to the Testut classification [9].
The exit point of the SN was determined as medial, middle and lateral according to its location on the superficially defined GT-SH line. Then, the following measurements were made in the subgluteal and posterior femoral regions;
– Distance (cm) of the SN exit point (EP) to the greater trochanter (GT-EP) and sacral hiatus (SH-EP).
– Distance of nerve blocking point to the greater trochanter (GT-BP, cm)
– Distance between SN exit point and BFR level (EP-BFR, cm)
– Distance between the lower border of gluteus maximus and BFR (GM-BFR, cm)
– SN exit point diameter (EPd, mm) and SN blocking point’s projection diameter determined on the superficial plane (BPd, mm)
– TN diameter (Td, mm) and CPN diameter (CPd, mm) at BFR level.
Statistical Analysis
Data obtained from lower limbs were analyzed by using SPSS 21.0 (IBM-Statistics software, Chicago Illinois) statistical program. Descriptive statistics (mean, standard deviation) were calculated for all parameters. The relationship between the parameters was determined by Pearson Correlation test. The significance level of statistical analyses was p<0.01 and p<0.05.
Ethical Approval
This study was approved by the Ethics Committee of Necmettin Erbakan University Non-Pharmaceutical and Non-Medical Device Research (Date: 2021-02-05, No: 2021/3091).
Results
In 19 of 20 lower extremities (95%), it was observed that the SN passed from the lower border of the piriformis to the gluteal region as a single root, and in 1 (5%) it branched before reaching the muscle. In this lower extremity, the CPN had pierced the piriformis and the TN was passing through the lower border of the piriformis and advancing towards the gluteal region (Figure 1). The SN was bifurcated in all (%100) of the lower extremities. The BFR level, determined according to thigh lengths, was detected in the distal 1/3 of the thigh in 7 extremities (35%), in the middle 1/3 of the thigh in 7 extremities (35%), and in the proximal 1/3 of the thigh in 6 extremities (30%)(Figure 2A-C). After BFR, connections between SN branches were detected in only two lower extremities (Figure 3A-B). The average measurement data of length, distance and thickness of 19 lower extremities were as follows:
Length measurements: LEL, 81.38±5.2cm; TL, 36.48±3cm.
Distances measurements: GT-SH, 18.47±1.52cm; GT-PSIS, 17.62±0.93cm; GT-EP, 10.02±1.35cm; GT-BP, 8.30±1.29cm; SH,-EP, 8.45±1.32cm; IT-EP, 5.41±1.36 cm; EP-BFR, 22.30±9.67cm; GM-BFR, 9.54±9.87cm; EP-FB, 8.35±3.99cm; EP-LB, 14.66±4.66cm.
Diameter measurements: EPd, 16.41±3.61mm; BPd, 12.56±3.11mm; Td, 5.06±0.99mm; CPd, 3.33±0.85mm.
The origin of the SN was medial to the midpoint of GT-SH in 16 cases (0.5-4.15cm), over the middle in one case, and lateral to the midpoint in three cases (0.5cm). The blocking point determined according to the classical SN blocking technique (back) was approximately 2cm closer to the greater trochanter than the exit point. The SN was, on average, 4mm thinner at the site of the blocking point than at the exit point, and the thicker terminal branch was TN in all cases.
GT-PSIS and GT-BP correlated with each other (r=0.567, p=0.011). GT-PSIS with TL (r=0.641, p=0.003) and GT-BP with TL (r =0.703, p=0.001) were found to have a statistically significant correlation. A positive and significant correlation was observed between the diameter of the SN at its exit point and its diameter at the blocking point (r=0.649, p=0.003). No significant relationship was detected between TL and total LEL of the TN and CPN.
Discussion
The SN is significant clinically because of its long course (gluteal, subgluteal, and posterior femoral region) and wide innervation area. In addition, the relationship of the nerve with the piriformis, as well as injuries that occur during invasive procedures (superficial and deep injections, abscess drainages, hip joint surgery, etc.) applied to the area, may cause sensory and motor disorders [6, 8, 12, 13].
The first classification based on the relationship between the piriformis and SN and referenced in many studies belongs to Beaton and Anson [1, 5, 8, 13, 14]. Barbosa et al. [1] made the most comprehensive classification in a systematic review that included 12 studies. Beaton and Anson [5] defined 7 types (1 normal, Type a; 6 variations, Type b-g) for SN and accepted that SN occurs in all cases. Barbosa et al. [1] described 13 types. In 10 of these types, the SN was formed before the piriformis (in 3 types, arising as a single root; in 7 types, early branched before the piriformis and branches not fused distally); in 2, formed distally and in one, not formed (Table 1).
The incidence of SN with a standard course was reported as 71.87% – 98.3% in cadaver and imaging studies [1, 2, 4, 7, 9, 14-17, 21, 24]. The second most common (1.7-22.5%) muscle-nerve relationship is the emergence of the peroneal root from the inside of the piriformis and the tibial root from the infrapiriform foramen. However, in these cases, Beaton and Anson [5] stated that these roots combined to form SN (Type b), while Barbosa et al. [1] mentioned that the roots continue as separate nerves (Type 3) (Table 1). Although it is argued in the literature that SN variations have a strong relationship with piriformis syndrome, Barbosa et al. [1] stated that there may be variations in asymptomatic patients, and on the contrary, these variations may not be found in symptomatic patients.
Most researchers stated that the SN and its branches emerge from the superior, inferior, or inside of the piriformis [1, 5, 7, 10, 13, 14-17]. Natsis et al. [8] reported that the piriformis had two (superior, inferior) or three bellies (superficial, medium, deep), while Jacomo et al. [18] mentioned accessory piriformis. Huang et al. [19] identified a connecting branch from the TN passing through the infrapiriform foramen to the CPN passing through the inside of the piriformis in a lower extremity during routine cadaveric dissection. They described this case as the reoccurrence of a split of SN. In our study, we observed that in 19 lower extremities (95%), the SN emerged as a single root from the infrapiriform foramen, while in one extremity (5%), the SN bifurcated early into terminal branches, the CPN emerged from the inside of piriformis, and the TN arose from the infrapiriform foramen, and these branches did not join. This type is suitable for Type b, according to Beaton and Anson [5], and Type 3 because the SN bifurcated early, according to Barbosa et al. [1]. The frequency of this variation detected in our study is close to the lower limit (4.1-22.5%) of incidence rates in adults reported in the literature.
Although it has been reported that the SN divides into two terminal branches by bifurcation [4,7,20,20-22], Berihu and Debeb [2] mentioned 5.36% trifurcation (TN, CPN and accessory nerve). It was determined that the SN was bifurcated into two branches in all lower extremities included in our study (100%). Cadaveric studies report differences in the level of bifurcation of the SN, but there is no standard classification [4,7,16,20,21](Table 2). In three of these studies describing the BFR level, the level was stated in the lower 1/3 of the thigh, while in the others it was frequently stated in the popliteal fossa (Table 2). Güvençer et al. [7] identified BFR in the popliteal fossa (52%) and the pelvis (48%). Ogeng’o et al. [16] frequently (67.1%) found BFR in the popliteal fossa. Barbosa et al. [4] defined BFR level according to the popliteal fossa and most frequently detected it below the apex of the popliteal fossa (67.96%) (Table 2). In our cadaveric study with a relatively small sample size, BFR levels detected in the upper 1/3, middle 1/3, and lower 1/3 of the thigh were close to each other (35%, 35%, 30%, respectively). In an imaging study for popliteal SN block, the BFR level was reported to be approximately 6±2.7cm (0-11.5cm) above the popliteal fossa fold [27]. However, literature knowledge and our study data show that this level may be higher. We suggest that it would be useful to consider the TL along with the popliteal fossa in estimating the location of SN blockade in the region of the back of the thigh above the BFR level. According to our results, we recommend knowing different BFR levels for invasive interventions to the region, including nerve block, intervening with imaging methods, and using the thigh length as well as the popliteal fossa as a reference in cases where imaging is not possible (blindly). Between the terminal branches of the SN, connecting branches can be found along their course [9, 16]. Testut classified these connection branches in his book “Tratado de Anatomia Humana (1902)” [9]. Tubbs et al. [9] detected various connections between the terminal branches of the SN in 30 of 40 lower extremities of 20 cadavers and evaluated them according to the Testut classification. They reported that the neural connections detected in the majority of sides (75%) were always located within 20 cm of the greater sciatic notch and the presence of up to 3 communications in one connection pattern. Ogeng’o et al. [16] reported but did not classify connecting branches in 3.7% of 164 lower extremities. In our study, neuronal connections between terminal branches were detected in two left extremities (10%). There was a connection from CPN to TN (Type A according to the Tesut classification) in one of these extremities. In the other, there was a connection between the proximal and distal parts of the TN. In the second case, which was similar to Type G (the connection between proximal and distal portions of the nerve) according to the Testut classification, there was an additional joint branch arising from the connecting branch. Since the number of studies on connection branches in the literature is limited, a comprehensive comparison could not be made.
Success in hip arthroscopy is closely related to the location of the opened ports [12, 13]. Especially in the posterolateral approach, the SN should be protected due to its proximity to the portal opened adjacent to the posterior and upper part of the apex of the greater trochanter [13]. In three of our cases, the origin of the SN was lateral to the midpoint of the GT-SH, and in the others it was medial. In surgical intervention or nerve block where ultrasonography cannot be used, the superficial projection of the SN from the exit site is determined, and its course is estimated. There are a limited number of studies conducted on adults, including lower extremity lengths, distances between some reference structures (posterior superior iliac spine, greater trochanter, ischial tuberosity, sacral hiatus) and SN thickness [15, 17, 24] (Table 3).
Compared to other studies evaluating similar parameters in samples with almost the same limb lengths, the GT-PSIS distance was longer and the bifurcation level of the SN was higher in this study (Table 3). Additionally, in our study, the relationship between the bifurcation level of the SN and the lower border of the gluteus maximus was evaluated; It was observed below the lower border (1.19-23cm) in 13 cases, above the lower border [(-3.7)-(-13)cm] in four cases, and at the lower border (0cm) in three cases. This study found significant correlations between the distance of the SN blocking point determined by the trans gluteal SN block technique to the greater trochanter, the lower extremity length, and the GT-PSIS. This relationship supports the use of the greater trochanter in determining the SN blocking point. However, there was no significant relationship between nerve thickness and lower extremity lengths. This result was incompatible with the expectation that the nerve thickness would be higher in tall people.
Limitation
Since it became very difficult to obtain cadavers during the COVID-19 epidemic, the low number of samples limited our study. On the other hand, the strength of our research is the comparison of classifications found in the literature and obtaining morphometric data.
Conclusion
The literature review observed that the relationship variations between SN and piriformis muscle, which have been defined since long ago, have recently been added to new ones. It is concluded that not all individual differences have yet been defined, so current and extended variation classifications may change. While we support using the greater trochanter as a reference in determining the point of SN blockade, we suggest that it would be useful to consider the TL together with the popliteal fossa in estimating the location of SN blockade on the posterior thigh.
Acknowledgment
The authors sincerely thank those who donated their bodies to science so that anatomical research could be performed.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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2. Berihu BA, Debeb YG. Anatomical variation in bifurcation and trifurcations of sciatic nerve and its clinical implications: In selected university in Ethiopia. BMC Res Notes. 2015;8:633.
3. Lewis S, Jurak J, Lee C, Lewia R, Gest T. Anatomical variations of the sciatic nerve, in relation to the piriformis muscle. Translational Research in Anatomy. 2016;5:15-19.
4. Barbosa FT, Barbosa TRBW, Cunha RM da, Rodrigues AKB, Ramos FW da S, Sousa-Rodrigues CF de. Anatomical basis for sciatic nerve block at the knee level. Braz J Anesthesiol. 2015;65(3):177-179.
5. Beaton LE, Anson BJ. The relation of the sciatic nerve and of its subdivisions to the piriformis muscle. Anat Rec. 1937;70(1):1-5.
6. Bretonnier M, Lemée J-M, Berton J-E, Morandi X, Haegelen C. Selective neurotomy of the sciatic nerve branches to the hamstring muscles: An anatomical study. Orthop Traumatol Surg Res. 2019;105(7):1413-1418.
7. Güvençer M, Iyem C, Akyer P, Tetik S, Naderi S. Variations in the high division of the sciatic nerve and relationship between the sciatic nerve and the piriformis. Turk Neurosurg. 2009;19(2):139-144.
8. Natsis K, Totlis T, Konstantinidis GA, Paraskevas G, Piagkou M, Koebke J. Anatomical variations between the sciatic nerve and the piriformis muscle: A contribution to surgical anatomy in piriformis syndrome. Surg Radiol Anat. 2014;36:273-280.
9. Tubbs RS, Collin PG, D’Antoni AV, Loukas M, Oskouian RJ, Spinner RJ. Sciatic nerve intercommunications: new finding. World Neurosurg. 2017;98:176-181.
10. Marco C, Miguel-Perez M, Perez-Bellmunt A, Ortiz-Sagristà JC, Martinoli C, Möller I, et al. Anatomical causes of compression of the sciatic nerve in the pelvis. Piriform syndrome. Revista Española de Cirugía Ortopédica y Traumatología (English Edition). 2019;63(6):424-430.
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12. Ciloğlu O, Karaali E, Görgülü FF, Toğrul E. Evaluation of the relationship between stiffness and thickness of the sciatic nerve and clinical outcomes after total hip arthroplasty: A prospective case-controlled study. Acta Orthop Traumatol Turc. 2021;55(6):500-507.
13. Gomes BA, Ramos MRF, Fiorelli RKA, Almeida CR de, Fiorelli SKA. Topographic anatomical study of the sciatic nerve relationship to the posterior portal in hip arthroscopy. Rev Colégio Bras. 2014;41:440-444.
14. Smoll NR. Variations of the piriformis and sciatic nerve with clinical consequence: A review. Clin Anat. 2010;23(1):8-17.
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Alperen Doguhan Oguz, Ismihan Ilknur Uysal, Betul Digilli Ayas, Ahmet Safa Goksan. Overview of clinical anatomy of the sciatic nerve: Re-evaluation with a cadaveric study. Ann Clin Anal Med 2024;15(11):753-758
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Outcomes of completion thyroidectomy in well-differentiated thyroid cancers: A retrospective clinical study
Ferdi Cambaztepe 1, Enes Ağırman 2, Müfide Nuran Akçay 1, Erdem Karadeniz 1, Metin Yıldız 1, Rıfat Peksöz 1, Sabri Selçuk Atamanalp 1
1 Department of General Surgery, Atatürk University Research Hospital, 2 Department of General Surgery, Erzurum City Hospital, Erzurum, Turkey
DOI: 10.4328/ACAM.22207 Received: 2024-03-30 Accepted: 2024-06-03 Published Online: 2024-08-07 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):759-762
Corresponding Author: Enes Ağırman, Department of General Surgery, Erzurum City Hospital, Erzurum, Turkey. E-mail: agirman_enes@hotmail.com P: +90 507 943 42 82 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0289-1252
Other Authors ORCID ID: Ferdi Cambaztepe, https://orcid.org/0000-0003-4754-776X . Müfide Nuran Akçay, https://orcid.org/0000-0001-8470-1741 . Erdem Karadeniz, https://orcid.org/0000-0002-8190-1163 . Metin Yildiz, https://orcid.org/0000-0002-8180-2827 . Rıfat Peksöz, https://orcid.org/0000-0003-4658-5254 . Sabri Selçuk Atamanalp, https://orcid.org/0000-0003-2561-6461
This study was approved by the Ethics Committee of Erzurum Atatürk University, Faculty of Medicine (Date: 2022-02-24, No: No:2022/2-2-08)
Aim: In patients with suspected follicular or Hürtle cell neoplasia in the pre-surgery fine needle aspiration biopsy, who are found to have compatible malignancy after unilateral surgery, complementary thyroidectomy can be performed. We aimed to evaluate the malignancy rate and complications following complementary thyroid surgery in light of the current literature.
Material and Methods: Complementary thyroidectomy was performed in 85 patients with pathology compatible with differentiated thyroid cancer after lobectomy-isthmectomy. These procedures were part of a retrospective analysis of 204 patients with suspected follicular or Hürtle cell neoplasia between January 2016 and June 2021. The pathology results after completion thyroidectomy and surgical complications within 1 year postoperatively were evaluated.
Results: After unilateral lobectomy-isthmectomy was performed on 204 patients, 85 patients whose final pathology results were compatible with differentiated thyroid cancer were retrospectively screened. The initial pathology results were divided into three groups: microinvasive tumors, tumors with a diameter of 4 cm or less, and tumors with a diameter greater than 4 cm. Their rates were 22.3%, 57.7% and 20%, respectively. The number of patients whose pathology results were compatible with differentiated tumor after completion thyroidectomy were 5, 15 and 7, respectively. Postoperative complications were evaluated as early (within the first 6 months) and late (after 6 months). In the surgical area, hematoma was seen in 8.2% of patients, transient hypocalcemia in 2.3%, and temporary hoarseness in 2.3%. There were no patients with permanent hypocalcemia or hoarseness.
Discussion: The decision to perform complementary thyroidectomy should be based on the pathology results after lobectomy-isthmectomy to avoid the complications associated with secondary thyroidectomy.
Keywords: Complementary Thyroidectomy, Complication, Follicular Neoplasia, Hürtle Cell Neoplasia, Isthmectomy-Lobectomy
Introduction
Complementary thyroidectomy is a surgical procedure. It can be performed on patients who have undergone thyroid surgery due to benign pathology, if the result is compatible with malignancy or if recurrence occurs after malignancy. Moreover, if pre-surgery fine needle aspiration biopsy suggests suspected follicular or Hürtle cell neoplasia and malignancy is confirmed after unilateral surgery, complementary thyroidectomy can be performed.
In most centers, subtotal thyroidectomy is still performed for thyroid diseases caused by benign conditions or suspected malignancy. Complementary thyroidectomy has higher rates of complications compared to initially planned unilateral surgery [1]. Hoarseness due to recurrent laryngeal nerve (RLN) paralysis and temporary or permanent hypocalcemia due to hypoparathyroidism are among the common complications [2]. Complications are often due to adhesions developed during the first surgery and anatomical changes due to neck exploration.
Complementary thyroidectomy performed after lobectomy-isthmectomy in patients whose histopathology results are compatible with differentiated thyroid cancers reduces the rate of local recurrence. It increases survival. It makes tracking easy. It prevents the possibility of differentiated thyroid tumors transforming into undifferentiated thyroid tumors and protects the patient from the risk of a second surgical operation [3].
In this study, patients with suspected follicular or Hürtle cell neoplasia on fine needle aspiration biopsy and who underwent unilateral lobectomy-isthmectomy were examined. Complementary thyroidectomy was performed on patients with malignant histopathological results. We aimed to evaluate the malignancy rate and complications following complementary thyroid surgery.
Material and Methods
Between January 2016 and June 2021, 204 patients who underwent lobectomy-isthmectomy were analyzed retrospectively in the Department of General Surgery at Ataturk University Faculty of Medicine. Patients suspected of follicular or Hürtle cell neoplasia based on preoperative fine needle aspiration biopsy and subsequently underwent unilateral lobectomy-isthmectomy were included in the study.
Patients whose histopathology results were compatible with differentiated thyroid tumors were divided into 3 groups based on tumor diameter. The first group included microinvasive carcinoma, the second group consisted patients with a tumor diameter of 1-4 cm, and the third group consisted patients with a tumor diameter of more than 4 cm. Complementary thyroidectomy was performed on total of 85 patients with differentiated thyroid cancer.
The patients were followed up for one year postoperatively. Major complications such as hematoma in the surgical field, permanent or transient hoarseness, and permanent or transient hypocalcemia due to hypoparathyroidism (HP) were monitored in the early postoperative period. If these complications persisted for longer than six months, they were considered permanent.
Ethical Approval
This study was approved by the Ethics Committee of Erzurum Atatürk University, Faculty of Medicine (Date: 2022-02-24, No: No:2022/2-2-08).
Results
We retrospectively reviewed 204 patients who underwent lobectomy-isthmectomy in the past 5 years. Fine-needle aspiration biopsy results were consistent with the suspicion of follicular or Hürtle cell neoplasia, and unilateral lobectomy-isthmectomy was performed on 204 patients. Complementary thyroidectomy was performed in patients whose pathology results were compatible with differentiated thyroid cancer. The general complaints of the patients included swelling and pain in the neck. Patients were informed that unilateral thyroidectomy and isthmectomy would be performed before the first surgery, and then, depending on the final pathology result, complementary thyroidectomy migh be required.
Among the patients whose final pathology result was compatible with differentiated thyroid cancer, 19% were male (16), 81% were female (69), and the mean age was 54.5 in men and 46.8 in women. Patients were divided into 3 groups based on the pathology results. The first group was the group with microinvasive cancer and consisted of 19 patients (22.3%). The second group was the group with a tumor diameter of 1-4 cm, 49 patients (57.7%). The third group was the group with a tumor diameter of 4 cm or larger, 17 patients (20%). Complementary thyroidectomy was performed on these patients.
Complementary thyroidectomy pathology results of 19 patients with microinvasive tumors after completion thyroidectomy indicated that there were papillary microcarcinoma in 4 patients, papillary carcinoma in 1 patient, Hürtle cell adenoma in 1 patient, adenomatous hyperplasia in 11 patients and tumor negative tissue in 2 patients. Pathology results of 49 patients who underwent complementary thyroidectomy with tumors ranging from 1-4 cm in diameter revealed papillary microcarcinoma in 15, adenomatous hyperplasia in 17, nodular hyperplasia in 4, parafollicular (C-cell) hyperplasia in 4, chronic lymphocytic thyroiditis in 6 and consistent with tumor-negative tissue in 3 patients (Table 1).
Pathology results of 17 patients who underwent complementary thyroidectomy with tumors 4 cm or larger in diameter revealed papillary microcarcinoma in 5, papillary carcinoma in 2, parafollicular C-cell hyperplasia in 2, nodular hyperplasia in 1, adenomatous hyperplasia in 4 and consistent with tumor-negative tissue in 3 patients (Table 1).
There were 7 patients (8.2%) with hematoma in the surgical area in the early postoperative period, 2 patients (2.3%) with transient hypocalcemia, and 2 patients (2.3%) with transient hoarseness. Open hematoma evacuation was performed on 1 of the patients who developed hematoma, needle aspiration was applied to 6 of them and anti-inflammatory was started. There were no patients with persistent hypocalcemia or hoarseness.
Discussion
The most common form of thyroid tumor is follicular adenoma [4]. Fine-needle aspiration biopsy is a valuable method for thyroid nodules, and the diagnostic accuracy rate in the detection of thyroid cancers before surgery was found to be %83.3 [5]. Capsular or vascular invasion must be demonstrated to differentiate between follicular or Hürtle cell neoplasia and carcinoma. It is not possible to show this in fine needle aspiration biopsy. The risk of malignancy in follicular neoplasia is accepted as 15-20%, and pathological examinations performed during surgery are inconclusive [6, 7].
Considering the possibility of benign pathology in patients with suspected follicular or Hürtle cell neoplasia, lobectomy-isthmectomy was performed on patients with suspicious fine needle aspiration biopsy results, and pathology results consistent with malignancy were reported in 85 (41%) of 204 patients.
The pathology results were categorized into three groups based on tumor diameter: microinvasive tumors, tumors with a diameter of 1-4 cm, and tumors over 4 cm in diameter. Among the 85 patients who underwent complementary thyroidectomy, pathology revealed malignancies in 5 out of 19 patients with microinvasive carcinoma, 15 out of 49 patients with tumors ranging between 1-4 cm in diameter, and 7 out of 17 patients with tumors 4 cm or larger in diameter. In total, 27 out of 85 patients (31%) were diagnosed with malignancies. The remaining 58 (69%) patients had pathology results consistent with benign disease.
The literature recommends performing a total thyroidectomy if a preoperative diagnosis of papillary carcinoma is made. If the pathological diagnosis is compatible with papillary thyroid carcinoma after partial thyroidectomy, completion thyroidectomy is recommended. [8, 9].
Complications after completion thyroidectomy include permanent and temporary hypocalcemia, permanent and temporary vocal cord paralysis due to recurrent nerve damage, and hematoma at the wound site. In the literature, the rates of temporary and permanent hypocalcemia after reoperative thyroid surgery are reported to be between 3-15% and 0-3.5%, respectively [9].
Permanent hypocalcemia was not observed in our study. Two patients (2.3%) with transient hypocalcemia were detected. Permanent and temporary vocal cord paralysis due to recurrent nerve damage has been reported in the literature at a rate of 1.4-4.4% after reoperative thyroid surgery [10,11]. In our study, we did not have any patients with persistent hoarseness. Two patients (%2.3) with transient hoarseness were detected.
There is no consensus on the ideal time required for complementary thyroidectomy. In the literature, surgery is recommended within the first 7-90 days or after 90 days [12, 13]. In our clinic, the average interval between two surgeries is the first month. Considering that the first pathology result comes out approximately 15 days later and the patient’s anxiety in patients with malignant pathology results is taken into consideration, the appropriate time period has been determined as the first month by our clinic. Postoperative bleeding and hematoma are also possible complications in patients undergoing thyroid surgery. Although it depends on the severity of the bleeding, the need for urgent exploration is rare [14, 15]. In our clinic, there was no bleeding requiring urgent exploration after completion thyroidectomy, and hematoma drainage was performed in 1 patient on the postoperative second day. Needle aspiration was performed on 6 patients.
According to the literature, the reasons why our complication rates are low include the fact that all surgical operations were performed by us, the parathyroid glands were fully explored during surgery and our clinic’s experience in parathyroid surgery, the exploration and preservation of the recurrent laryngeal nerve in all thyroid surgeries, and the contralateral side in patients who underwent lobectomy-isthmectomy, avoiding entering the thyroid lodge. Additionally, performing vocal cord examination on all our patients before thyroid surgery, and the long-term acceptance of our center as a center in thyroid surgery, and its high experience in thyroid surgery.
Conclusion
The traditional surgical approach to patients with suspected follicular or Hürtle cell neoplasia based on fine needle aspiration biopsy is hemithyroidectomy to the side of the neoplasia. We believe that the decision for completion thyroidectomy should be based on the final pathology result, to protect patients from temporary and permanent complications of secondary thyroidectomy and due to the high rate of co-occurrence of papillary thyroid carcinoma with follicular and Hürtle cell neoplasia.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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Ferdi Cambaztepe, Enes Ağırman, Müfide Nuran Akçay, Erdem Karadeniz, Metin Yıldız, Rıfat Peksöz Sabri Selçuk Atamanalp. Outcomes of completion thyroidectomy in well-differentiated thyroid cancers: A retrospective clinical study. Ann Clin Anal Med 2024;15(11):759-762
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Epidemiology of pediatric electrical injuries of a tertiary city hospital in Istanbul: Five years of experience
Yakup Çağ 1, Mehmet Tolga Köle 1, Aydan Erdem 1, Kemal Pişmişoğlu 1, Ufuk Yükselmiş 2, Fatih Çiçek 1, Murat Dereli 3, Feyza Esen 4, Yasemin Akın 1
1 Department of Pediatrics, 2 Department of Pediatric Intensive Care, 3 Department of Pediatric Surgery, 4 Department of Pediatric Emergency, University of Health Science, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.22221 Received: 2024-04-14 Accepted: 2024-05-20 Published Online: 2024-08-23 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):763-767
Corresponding Author: Yakup Çağ, Department of Pediatrics, University of Health Science, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey. E-mail: yakupcag@hotmail.com P: +90 542 311 88 53 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3855-7280
Other Authors ORCID ID: Mehmet Tolga Köle, https://orcid.org/0000-0002-6055-7746 . Aydan Erdem, https://orcid.org/0000-0001-8541-4699 . Kemal Pişmişoğlu, https://orcid.org/0000-0001-7278-309X . Ufuk Yükselmiş, https://orcid.org/0000-0003-1150-2586 . Fatih Çiçek, https://orcid.org/0000-0001-7348-7081 . Murat Dereli, https://orcid.org/0000-0002-4433-8922 . Feyza Esen, https://orcid.org/0000-0003-0759-2646 . Yasemin Akin, https://orcid.org/0000-0002-7618-7778
This study was approved by the Ethics Committee of Istanbul Kartal Dr. Lütfi Kırdar City Hospital (Date: 2022-02-22, No: 2022/514/220/15)
Aim: Despite being preventable with simple measures, electrical injuries are a significant public health issue that can lead to high morbidity and, rarely, death. In this study, the aim was to evaluate the demographic, laboratory, and clinical characteristics of children who presented to our emergency department with electrical injuries, as well as the associated complications.
Material and Methods: Electrical injuries were divided into two groups based on the type of voltage, and the recorded data were compared between these two groups.
Results: A total of 146 patients were included in the study, with 97 of them being male. 62.3% of the patients were under the age of 5. Electrical injuries frequently occurred at home (74.7%) and were often associated with electrical outlets (63.7%). One patient died. Surgical intervention was performed in 15 patients. We identified burns in 83 patients due to electrical accidents. Among the patients, 71 had low-voltage injuries, and 12 had high-voltage injuries. There was a statistically significant difference in burn severity based on voltage status. High-voltage injuries were associated with statistically higher levels of leukocytes, neutrophils, creatine kinase, aspartate aminotransferase , alanine aminotransferase, and creatinine compared to low-voltage injuries. A positive correlation was observed between creatine kinase levels and the total length of hospital.
Discussion: The frequency of high-voltage injuries increased with age, and these patients experienced more severe burns, greater tissue trauma, and required more surgical interventions. To minimize the occurrence of such cases, it is crucial to educate families and implement legal measures by governments.
Keywords: Electrical Injury, Voltage, Burn, Children, Precaution
Introduction
Despite being preventable with simple safety measures, electric injuries (EIs) remain a significant public health issue with high morbidity and, in rare cases, even mortality [1]. Children consitute 20% of the patients presenting to emergency clinics due to EIs [2]. It has been noted that EIs are more commonly seen in boys than girls among children [1, 3, 4]. In studies, EIs have been classified as high-voltage (HV), low-voltage (LV), or lightning injuries [5, 6]. A HVI is defined as contact with a power source delivering 1000 V or more, while a LVI occurs when the power source bears less than 1000 V [7, 8].
The severity of EIs depends on factors such as the magnitude of voltage, intensity, pathway, current type, duration of contact, resistance of tissues at the point of contact, and individual characteristics [8, 9]. In LVI, burns are typically more superficial, and muscle damage is rare. In HVI, life-threatening cardiac arrhythmias can occur, leading to organ loss due to deep burns and compartment syndrome, kidney failure resulting from muscle destruction, multiple organ failure, and even life-threatening respiratory arrest [10].
The fact that the majority of EIs in children occur accidentally and are preventable highlights the importance of epidemiological data [11]. Nischwitz et al. [12] reported a decline in EIs with education and implementation of necessary precautions.
Our study aims to evaluate the demographic, laboratory, and clinical characteristics of patients who present to our pediatric emergency clinic with EIs, assess the associated complications, and describe the features and outcomes of these EIs.
Material and Methods
Medical records of patients under 18 years who presented to the Emergency Clinic with EIs at our hospital between June 2016 and June 2021 were reviewed retrospectively. The study was conducted following the Helsinki Declaration. Because of the retrospective nature of the study, signed informed consent was not obtained from patients’ families. Patients initially treated at other hospitals, those who were admitted for reconstructive surgery later, and those with missing data were excluded from the study. A total of 146 pediatric patients with EIs were included in our study.
The diagnosis of EI was determined based on the patient’s history and physical examination. Patients were placed under observation and received fluid resuscitation, burn and wound dressing, EKG, cardiac monitoring, and tetanus prophylaxis as needed. Patients were discharged after following up in the emergency room or admitted to the ward or intensive care unit, which is required depending on their clinical condition. Patients diagnosed with compartment syndrome during follow-up underwent immediate escharotomy or fasciotomy. First-degree and superficial second-degree burns were managed with dressings. The necrotic tissues were debrided, and skin grafts were applied in cases of deep second-degree and third-degree burns. In instances of extensive muscle necrosis, limb amputation was performed.
In our study, the demographic data of patients, causes of damage, location and extent of EI, type of electrical current, laboratory investigations, EKG, length of hospital stay, and clinical outcomes were recorded and evaluated in an Excel file.
EIs were classified into two groups based on the type of current: HVI (>1000 volts) and LVI (<1000 volts). The recorded data were compared between these two groups.
Statistics
The data were analyzed using the statistical package program IBM SPSS Statistics Standard Concurrent User V 26 (IBM Corp., Armonk, New York, USA). Descriptive statistics were presented as the number of units (n), percentage (%), mean ± standard deviation (mean ± SD), median (M), minimum (min), and maximum values. The normality of numerical variables was assessed using the Shapiro-Wilk normality test. Hematological values were compared between the (LV) and (HV) groups using the Mann-Whitney U test. Age and gender comparisons between voltage groups were performed using Fisher’s exact test. Subgroup comparisons for age were conducted using the Bonferroni-corrected two-sample z-test. The relationship between creatine kinase (CK) and length of hospital stay was evaluated using Spearman’s correlation coefficient. A p-value of less than 0.05 was considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Istanbul Kartal Dr. Lütfi Kırdar City Hospital (Date: 2022-02-22, No: 2022/514/220/15).
Results
A total of 146 patients presented to our emergency clinics with EIs, and 62.3% (n=91) of patients were preschool-aged (0-5 years), 22.6% (n=33) were school-aged children (6-12 years), and (15.1%) patients (n=22) were adolescents (13-18 years). The incidence of EIs was higher in males (66.4%, n=97) compared to females. EIs occurred frequently at home (n=109; 74.7%) and were frequently associated with contact with electrical outlets (63.7%, n=93) . Among the patients, 91.1%(n=133) were exposed to LV and 8.1% (n=13) to HV. Upper extremities were the most common entry site of the electrical current (83.6%, n=122), followed by the lower extremities (8.9%, n=13.) During EKG monitoring, sinus tachycardia was observed in 4 patients, where non-specific EKG changes were noted in 1 patient. While 36 patients were admitted to the burn unit, 18 patients were admitted to the intensive care unit. One patient died during the follow-up period (Table.1). Surgical intervention was performed in 15 patients (10.3%) following EIs. A total of 5 patients received debridement and subsequent flap surgery to the fingers (all patients), the lip (one patient), the upper extremity (one patient), and the thigh regions (one patient.) Also, four patients underwent escharotomies on the thigh, and two patients underwent escharotomies on the upper extremity, where one patient with extensive necrotic areas required finger amputation.
We detected burn injuries related to electrical accidents in 83 patients (56.8%), and 71 patients (85.5%) were exposed to LV, while 12 patients (14.5%) were to HV. Among the patients, 54 had 1. degree burns, 14 had 2. degree burns, and 15 had 3. degree burns. A statistical difference was found in terms of burn severity based on the voltage status (p <0.001) (Table.1).
A statistical difference was found in age group distribution based on voltage status. (p=<0.001) (Table 2). The number of 0-5 year old patients in the LV group was statistically higher than the 13-18 year old group. In the HV group, the number of patients in the 13-18 age group was statistically more than the 0-5 age group. The incidence of HVI increased with age. According to Table 3, we observed that the patients in the HV group have statistically more elevated levels of leukocytes (WBC), neutrophils, CK, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine compared to the patients in the LV group. Additionally, a positive correlation was observed between CK levels and the total length of hospital stay (rho=0.395; p=0.003).
Discussion
EIs can cause minor tissue injuries at the entry and exit points as well as life-threatening severe tissue damage [4]. The severity of electrical damage varies depending on the magnitude of the current, the resistance of the body, the path of the current through the body, and the duration of contact with the current source [13]. While EIs are more frequently observed in developing countries, a study reported an annual EI rate of 17.5% in Kosovo, 3% in the United States, 3-5% in China, and 3% in Europe [14].
Studies have emphasized that in children, EIs leading to emergency department visits are more common in boys under the age of 5 [1, 5, 15]. In a study conducted in Turkey by Özdel et al. [10] 74% of the patients presenting to the emergency clinic with EIs were male. In a study by Buja et al. [14] in Kosovo involving 182 patients, 93% of patients were male, while in another study conducted in Austria, 74.1% were male. [16]. Consistent with the literature, our study also revealed a higher incidence of EIs in males (n = 97; 66.4%) compared to females. We believe that the greater interest of male children in electrical and electronic devices may contribute to these injuries.
EIs are more commonly seen between the ages of 4.5 and 8.7 [5, 10, 15]. In our study, the average age was 5.11 years, and in line with the literature, 91 patients (62.3%) were under five years old [10, 17]. Taking domestic precautions during the preschool period, when children have excessive curiosity and a desire to explore, supporting parents with education on this issue, and enforcing legal standards are crucial in preventing EIs. Young children are typically exposed to LVI by coming into contact with electrical cables or electrical outlets. On the other hand, older children may develop EIs by coming into contact with HV power lines in the workplace or industrial electrical currents [17]. Consistent with the literature, our study found that LVI primarily affected preschool and school-aged children, while HVI were also more prevalent among adolescents. In our study, 74.7% of EIs occurred at home, and 63.7% occurred in young children following contact with electrical outlets.
We predominantly observed LVI (91.1%) in our study. Çağlar et al. [1] study in Turkey reported that 92.1% of the cases had LVI. Furthermore, this study revealed that 86.8% of EIs occurred at home, with electrical outlets accounting for 39.5% of the cases.
Although EIs constitute approximately 4% of total admissions to burn centers, they are associated with high morbidity and mortality rates [4]. They are the leading cause of amputations performed in burn centers [8]. In our study, we observed electrical burns in 83 patients (56.8%). Among them, 71 patients (85.5%) were exposed to LV, while 12 patients (14.5%) were to HV. We observed third-degree burns in 10 patients who had HVI. In our study, a statistical difference was found in terms of burn severity according to the voltage status (p=<0.001). Another study conducted in our country, based on eight years of data, yielded similar results to our study, indicating that HVI resulted in more profound and broader burn areas compared to LVI [18]. Lack et al. [5] reported similar findings, highlighting larger burn areas with HVI in South Africa. In HVI, patients underwent more surgical interventions, amputations, and flap surgeries, resulting in prolonged hospital stays [19]. Compartment syndrome can develop in the extremities as a consequence of EIs. Early escharotomy/fasciotomy should be performed to prevent amputations and achieve decompression [4]. In our study, one patient underwent amputation, and six underwent escharotomy as a preventive measure against compartment syndrome.
Electric current can lead to injuries in specific organ systems, including cardiac arrhythmias, skin injuries, rhabdomyolysis, and acute kidney injury [5]. Maghsoudi et al. [20] have noted that renal failure can develop in these patients due to the deposition of myoglobin and cellular fragments as a result of severe damage to deep tissues and muscles. Rapid and aggressive resuscitation, fluid support therapy, and urine alkalization have prevented renal failure. Furthermore, studies have indicated long-term complications following EIs include cataracts, transverse myelitis, amyotrophic lateral sclerosis, post-traumatic stress disorder, depression, and psychological and neurological disorders [21, 22]. After EIs, EKG changes such as sinus tachycardia, non-specific ST changes, heart blocks, prolonged QT interval, supraventricular-ventricular arrhythmias, and atrial fibrillation are commonly observed, while asystole and ventricular fibrillation are the life-threatening consequences of EIs [23]. Studies have emphasized that tissue damage increases as the voltage exposure increases [10]. Following up on patients with EIs for 24-hour cardiac monitoring as a standard practice is no longer recommended. Research has indicated that even in cases with HV current, patients with stable heart rhythm and no risk factors do not require cardiac monitoring during the 24 hours following the injury [20]. We did not observe significant cardiac damage or rhythm abnormalities during the monitoring.
While passing through the pathway, electrical current can cause damage to deep tissues, leading to elevated levels of particular laboratory markers. Yılmaz et al. [24] found significantly higher levels of CK, CK-MB (creatine kinase myocardial band), AST, and ALT in patients with HVI compared to those with LVI, suggesting that these parameters could serve as indicators of tissue damage. Another study conducted in Turkey also reported significantly higher levels of CK, CK-MB, AST, and ALT in patients exposed to HV compared to those exposed to LV [10]. Additionally, markers of rhabdomyolysis, such as myoglobin and CK, have been associated with injury severity, amputation rate, and mortality [18]. Shih et al. [25] in a comprehensive study encompassing 41 studies and 5,485 patients worldwide, reported that patients presenting with HVI had prolonged hospital stays, more EKG changes, and a higher incidence of myoglobinuria and kidney failure. We observed that the levels of CK, AST, ALT, and creatinine in the HV group were statistically higher than those in the LV group in our study. Additionally, a positive correlation was observed between CK levels and the total length of hospital stay (p=0.003).
Limitation
It is a single-center and has a retrospective nature. Also, we could not assess long-term morbidity, neurological sequelae, psychological impact, and social adaptation issues following EIs. However, Having 5 years of data from our hospital, which is one of the major burn centers in the region, is a strong aspect of our study.
Conclusion
EIs continue to be a grave concern in children. They range from minor injuries to life-threatening multiple organ injuries. In our study, when considering the age groups, EIs were predominantly observed in the home environment and among boys aged ≤5 years. It is crucial to address them as a public health concern and design national strategies to reduce EIs. Preventative measures and regular education programs for families and children play a significant role in preventing EIs.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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Download attachments: 10.4328.ACAM.22221.pdf
Yakup Çağ, Mehmet Tolga Köle, Aydan Erdem, Kemal Pişmişoğlu, Ufuk Yükselmiş, Fatih Çiçek, Murat Dereli, Feyza Esen, Yasemin Akın. Epidemiology of pediatric electrical injuries of a tertiary city hospital in Istanbul: Five years of experience.Ann Clin Anal Med 2024;15(11):763-767
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Evaluation of plasma total antioxidant, total oxidant, thiol-disulphide and optical coherence tomography data in fibromyalgia patients
Mustafa Tuna 1, Alparslan Yetişgin 1, Müslüm Toptan 2, Adnan Kirmit 3
1 Department of Physical Medicine and Rehabilitation, 2 Department of Ophthalmology, 3 Department of Biochemistry, Faculty of Medicine, Harran University, Şanlıurfa, Türkiye
DOI: 10.4328/ACAM.22247 Received: 2024-05-04 Accepted: 2024-07-29 Published Online: 2024-09-11 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):768-773
Corresponding Author: Mustafa Tuna, Department of Physical Medicine and Rehabilitation Faculty of Medicine, Harran University, Şanlıurfa, Türkiye. E-mail: mustafa5tuna@gmail.com P: +90 553 594 33 15 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6713-9352
Other Authors ORCID ID: Alparslan Yetişgin, https://orcid.org/0000-0003-3405-8596 . Müslüm Toptan, https://orcid.org/0000-0002-9795-8228 . Adnan Kirmit, https://orcid.org/0000-0003-2799-8416
This study was approved by the Ethics Committee of Harran University, Faculty of Medicine (Date: 2019-03-11, No: HRÜ/19.03.03)
Aim: We aimed to examine the relationship between OCT findings and oxidation and antioxidation balance, which is thought to have a role in the etiopathogenesis of the disease in patients with fibromyalgia.
Material and Methods: A total of 39 female patients with FMS and 41 healthy volunteers were included in the study. Plasma native thiol (NT), total thiol (TT), disulfide (DS), NT/TT, DS/NT, DS/TT, TOS, TAS and OSI values, and eye OCT measurements were evaluated. Regarding OCT measurements, the subfoveal choroid layer, retinal nerve fiber layer, ganglion cell layer, and macular thickness were assessed.
Results: When compared to the healthy control group, TAS, TOS, NT, TT, DS levels were high in the FMS patient group (all p<0.05), whereas other measurements were found to be similar (all p >0.05). The increase in TOS levels (p<0.001) in the FMS group was much more significant than the increase in TAS levels (p=0.030). In terms of OCT findings, there was no significant difference between the right and left eye subfoveal choroid thicknesses between the two groups (both <0.001).
Discussion: The increase in TOS levels suggests that the level of antioxidants for compensation of increased oxidant status also increases because it is much higher than TAS increase. Since the OSI values are similar, we can state that we did not detect an increase in oxidative stress. We think that FMS patients with high FIQ scores, symptoms, and complaints should be evaluated in terms of oxidative stress and related possible complications.
Keywords: Fibromyalgia Syndrome, Total Oxidant Status, Total Antioxidant Status, Oxidative Stress Index, Native Thiol, Total Thiol, Disulfide, Optical Coherence Tomography
Introduction
Fibromyalgia syndrome (FMS) is one of the most common causes of chronic widespread musculoskeletal pain, the etiopathogenesis of which has not yet been determined, and systemic symptoms are often accompanied. Autonomic nervous system dysregulation and increased oxidative stress are two of the many factors implicated in the etiopathogenesis [1].
During oxidative phosphorylation, where most of the body’s energy is produced, free oxygen radicals are formed. In the normal state, there is a balance between reactive oxygen species (ROS) and antioxidants in the intracellular, membranes and extracellular spaces. The increase in oxidative stress is due to the imbalance between oxidation products and antioxidant defense products. Parameters such as thiol/disulfide balance, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) are used to calculate the balance between oxidation and antioxidation. Thiols are important antioxidants and form reversible disulfide bonds with reactive oxygen radicals in order to balance oxidative stress in the body. It has an important role in many cellular activities such as thiol/disulfide homeostasis, maintenance of oxidant/antioxidant balance, detoxification, cellular signal transduction, transcription, cell growth and apoptosis. The etiopathogenetic role of changes in thiol/disulfide homeostasis in hypertension, preeclampsia, many autoimmune diseases, gastrointestinal and cardiovascular system diseases has been investigated previously. It is thought that imbalances in thiol/disulfide homeostasis cause an increase in oxidative stress products, leading to the emergence of diseases through inflammation [2, 3]. Although there are a limited number of studies in the literature examining the thiol/disulfide balance or TAS, TOS values in FMS, we found only one study in which both parameters were studied together [4].
Optical coherence tomography (OCT) devices can be used in the diagnosis and follow-up of diseases by obtaining high-resolution tomographic images in biological tissues, especially in the eye, without using any contrast agent or radiation[5,6]. The number of studies evaluating the OCT findings of patients with FMS is very limited [7].
In our study, we aimed to examine the relationship between OCT findings and oxidation and antioxidation balance, which is thought to have a role in the etiopathogenesis of the disease in patients with FMS. Despite our extensive literature review, our study is a first in this regard, as we have not found any publication examining the OCT findings of patients with FMS and the oxidant/antioxidant balance relationship.
Material and Methods
Female patients with FMS, aged 20-50 years, with old and new diagnoses, who applied to the Physical Medicine and Rehabilitation outpatient clinic between March 2019 and March 2020, and healthy volunteer women in the same age group were included in the study.
The participants in our study were divided into two groups as those with FMS and healthy volunteers. Demographic data of both groups were recorded. In addition, venous blood samples were taken from the forearm of the two groups and intraocular pressure was measured before the OCT procedure. The 2010 ACR diagnostic criteria, Fibromyalgia Impact Questionnaire (FIQ) and Visual Pain Scale (VAS) were filled in the FMS group.
A 5 cc tube blood sample of both groups included in the study was taken and stored at –80°C until the study time. Serum total oxidant, total antioxidant parameters and thiol/disulfite levels were studied considering the manufacturer’s recommendations and expiration dates.
In addition to the characteristics of all participants such as age, BMI, smoking, occupation, marital status, number of children, sports/exercise habits, duration of diagnosis and medical treatments of FMS patients were recorded.
In order to evaluate the central macular, optic nerve and choroidal thicknesses of all participants, SD-OCT recordings were made with the Heidelberg spectralis OCT device (Heidelberg Engineering, Heidelberg, Germany) in our hospital. All results were evaluated by the same ophthalmologist. In this evaluation, retinal nerve fiber thickness, ganglion cell layer thickness, subfoveal choroidal layer thickness and macular thickness were evaluated. In addition, in order to exclude retinal nerve fiber thickness and eye hypertension affecting other structures, eye pressures of all groups were measured before extraction and those less than 21 mmHg were included in the study. This study was produced in the specialization thesis.
Statistical Analysis
Statistical Package for the Social Sciences (SPSS) 20 for Windows package program (SPSS Inc., Armonk, NY USA) was used for data analysis. The Shapiro Wilk Test and histogram graphs were used to assess whether the data conformed to the normal distribution. Descriptive statistics were given as mean±standard deviation, median (minimum-maximum), or number and percentage. Numerical data between groups were compared using Student’s t test or Mann Whitney U test. Categorical data were compared using Chi-Square or Fischer’s Exact test. Pearson or Spearman correlation tests were used for correlation analysis. The relationship between the parameters that were significant between the groups was determined by multiple linear regression analysis. P<0.05 was considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Harran University, Faculty of Medicine (Date: 2019-03-11, No: HRÜ/19.03.03).
Results
39 women with FMS and 41 healthy volunteer women aged 20-50 years were included in the study. The mean age of all participants was 34.4±6.9 years, and their mean BMI was 24.5±2.8 kg/m2. The mean values of the right and left intraocular pressures of the participants were measured as 14.9±2.4mmHg and 14.7±2.7mmHg, respectively. While 82.1% (n=32) of FMS patients were married, 68.3% (n=28) of healthy volunteers were married. While 94.9% (n=37) of those with FMS were housewives, this rate was 43.9% in the other group. While there was no participant with a history of alcohol use, the rate of smoking was 20.5% (n=8) in the group with FMS, while this rate was 12.2% (n=5) in the healthy group.
The comparison of demographic and OCT measurement values of the group with FMS and the group consisting of healthy volunteers is shown in Table 1. In the OCT findings of both groups, only the right and left eye subfoveal choroidal thickness measurements were significantly different, and these two values were lower in the FMS group.
Comparative blood tests for the examination of oxidative stress parameters and thiol/difulfide balance of the two groups are summarized in Table 1. TOS and TAS values were found to be significantly higher in the group with FMS.
The correlations between demographic and clinical characteristics of FMS patients and healthy control group are summarized in Table 2. There was a negative correlation between the ages of all participants and their native and total Thiol values. FMS diagnosis time was not correlated with any blood or OCT finding, except for a positive correlation with TAS level. While there were no findings correlated with VAS, FIQ was positively correlated with OSI. Right and left eye RNFL measurements were negatively correlated with native thiol and total thiol only in the healthy group. It was determined that the macular thickness of the right and left eyes were negatively correlated with TAS levels only in the FMS group.
The relationship between oxidant-antioxidant results and eye findings, which differed significantly between the FMS group and the healthy control group, and FMS after excluding (normalizing) the effect of age, BMI, and smoking by regression analysis is summarized in Table 3.
Discussion
There are studies suggesting that oxidative stress disorder may play a role in the pathogenesis of fibromyalgia syndrome [4]. Increased oxidative stress results from an imbalance between oxidation products and antioxidant defense products. It has been stated that increased oxidative stress may lead to some inflammatory clinical conditions. Recent data suggest an association between oxidative stress and pain. Lipid peroxidation resulting from increased oxidative stress has been described in patients suffering from depression and fatigue, and these two typical symptoms are also frequently found in FMS patients [1, 4, 8].
In our study, in the OCT evaluation of the patients; Subfoveal choroidal thickness measurements were found to be significantly lower in both eyes of the FMS group compared to the healthy control group. However, the retinal nerve fiber layer, ganglion cell layer thickness and macular thickness were similar in both groups.
Compared with the healthy control group, total oxidant status and total antioxidant status were significantly higher in the group with FMS, but there was no significant difference in the oxidative stress index. In addition, while native thiol, total thiol and disulfide levels were high in patients with FMS, there was no significant difference between disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios.
No correlation was observed between subfoveal choroidal thicknesses and age, disease duration, FIQ, VAS and oxidative stress parameters in the group with FMS. A positive correlation was detected with native thiol and total thiol only in the left eyes of the healthy group. Native thiol and total thiol levels were negatively correlated with age in both groups. No correlation was found between TAS, TOS and OSI values and thiol/disulfide homeostasis parameters in both groups.
Ulusoy et al. He measured the eye choroidal thickness of patients with FMS with OCT [5]. In addition to the subfoveal region, which was our measurement site, he also examined the nasal and temporal areas. The finding of significant thinning in the choroidal thickness of the eyes in all three regions of the patients with FMS was considered as a result consistent with our study.
Endothelial dysfunction may occur in patients with FMS due to an overactive sympathetic nervous system. Choroidal layer thickness may be affected in these patients, since the control of choroidal blood flow is carried out by the autonomic nervous system and autonomic nervous system changes are observed in FMS. Sympathetic stimulation causes vasoconstriction and decreases choroidal blood flow, while parasympathetic stimulation increases blood flow by causing vasodilation via nitrous oxide. It has been shown that there is also a decrease in optic disc perfusion in patients with FMS. In patients with FMS, worsening of endothelial functions and arterial elasticity features was detected with the increase in FIQ score [9,10].
Endothelial dysfunction may have resulted in choroidal ischemia, resulting in thinning of the choroidal layer with an extensive vascular network. Thinning of the choroidal layer has also been detected in diseases that cause high sympathetic activity, such as chronic heart failure and coronary artery disease [11,12]. We believe that measuring the thickness of the choroidal layer of the eye with OCT, which is a non-invasive method in FMS patients, may be a stimulant for both the diagnosis of the disease and the prevention of future complications secondary to autonomic nervous system dysfunction.
In our study, there was no significant difference between the FMS and healthy groups in the retinal nerve fiber layer, ganglion cell layer and macular thickness. Garcia et al. OCT measurements of patients with FMS detected a significant thinning in the retinal nerve fiber layer, inner plexiform layer, and ganglion cell layers compared to the healthy group [6]. As a result of this study, in which the thickness of the choroid and macula layers was not evaluated, they mentioned the presence of axonal damage in the optic nerve due to thinning of the RNFL, and stated that it suggests the presence of neurodegenerative processes in FMS [6]. The fact that current OCT findings are not similar to our study may be related to patient selection.
Aktekin et al. reported that there was no significant difference in native thiol, total thiol, disulfide levels, disulfite/native thiol, disulfide/total thiol and native thiol/total thiol ratios, TAS, TOS, and OSI values between FMS patients and the control group [9]. As a result of their studies, they stated that they found that oxidative stress did not increase in FMS patients. In our study, we did not find a significant difference in OSI values, DS/NT, DS/TT and NT/TT ratios between FMS patients and healthy controls. Again, similar to the aforementioned study, we did not detect any correlation between TAS, TOS, OSI and thiol/disulfide balance parameters. Bozkurt et al. found a positive correlation between the FIQ values and TOS and OSI values of patients with FMS in their studies, but they did not detect a relationship with TAS [13]. In our study, the OSI value of the group with a FIQ value of >50 was significantly higher.
Unlike Bozkurt et al., there was no difference between the high FIQ group and the low group in terms of TOS, while the TAS level of the high group was low. Two studies show that there is a relationship between the severity of the disease and the oxidative stress state in FMS.
Antioxidants may be increased to prevent increased oxidative load in mitochondria from causing oxidative damage and deterioration [14]. Although the TOS level was significantly higher in the group with FMS in our study, we believe that the less significantly higher TAS level can be considered as an increased antioxidant status in response to the increased oxidant status. Since the patient group included in the study was relatively young, the OSI value may have been normal by providing compensation for the oxidation response.
Perhaps, if the older patient group had been chosen, antioxidant compensation would not have been sufficient and the OSI value would have been high. Fidan et al. and Karataş et al. found similar results in their studies. They showed that the native thiol level and native thiol/total thiol ratio increased, while the disulfide level and disulfide/native thiol and disulfide/total thiol ratios decreased in those with FMS [15,16]. In both studies, the mean age and BMI of patients with FMS were considerably higher than in our study. While Fidan et al. did not include any information about smoking in their study, Karataş et al. They stated that smoking status of FMS and the healthy group was similar. Fidan et al. Considering the thiol/disulfide balance, they stated that their results are compatible with the views supporting that FMS is more suitable for proliferative diseases than degenerative diseases and that oxidative stress does not increase.
As can be seen from these results, the results of the few studies examining the thiol/disulfide balance in FMS are contradictory [17], and it is clear that new studies with a high number of participants are needed.
The main limitation of our study was the relatively small number of participants. In addition, although smoking status was similar in the healthy and FMS group, the age, duration and amount of starting smoking were not evaluated. Another limitation of the study was the possibility that most of the patients in the FMS group were using drugs, which might affect the results. In addition, the lack of similar studies caused difficulties in comparing the results.
Conclusıon
In our study, for the first time, eye OCT findings of patients with FMS and blood oxidant-antioxidant parameters were examined together. Subfoveal choroidal thickness measurements were significantly lower in the patient group with FMS. In addition, we found that there was no significant difference in the retinal nerve fiber layer, ganglion cell layer thickness and macular thickness.
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 compareable ethical standards.
Funding: The financial support required for the study was provided by the Harran University Scientific Research Coordination Board (HUBAK).
Conflict of Interest
The authors declare that there is no conflict of interest.
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3. Ates I, Altay M, Yilmaz FM, Topcuoglu C, Neselioglu S, Erel O, et al. Dynamic thiol/disulfide homeostasis in patients with autoimmune subclinical hypothyroidism. Endocr Res. 2016;41(4):343-9.
4. Beyaztaş H, Aktaş S, Güler EM, Ata E. Oksidatif stres fibromiyalji hastalarının ağrı mekanizmalarında katkıda bulunan bir faktör olabilir. Reumatismo. 2023;75(3):121-127.
5. Ulusoy MO, Kal A, Işik-Ulusoy S, Kal Ö. Choroidal thickness in patients with fibromyalgia and correlation with disease severity. Indian J Ophthalmol. 2018;66(3):428-32.
6. Garcia-Martin E, Garcia-Campayo J, Puebla-Guedea M, Ascaso FJ, Roca M, Gutierrez-Ruiz F, et al. Fibromyalgia ıs correlated with retinal nerve fiber layer thinning. PLoS One. 2016;11(9): e0161574.
7. Pilar Bambo M, Garcia-Martin E, Gutierrez-Ruiz F, Magallon R, Roca M, Garcia-Campayo J, et al. Study of perfusion changes in the optic disc of patients with fibromyalgia syndrome using new colorimetric analysis software. J Fr Ophtalmol. 2015;38(7):580-7.
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11. Ahmad M, Kaszubski PA, Cobbs L, Reynolds H, Smith RT. Choroidal thickness in patients with coronary artery disease. PLoS One. 2017;12(6):e0175691.
12. Teberik K, Eski MT, Doğan S, Pehlivan M, Kaya M. Ocular abnormalities in morbid obesity. Arq Bras Oftalmol. 2019;82(1):6-11.
13. Bozkurt M, Caglayan M, Oktayoglu P, Em S, Batmaz I, Sariyildiz MA, et al. Serum prolidase enzyme activity and oxidative status in patients with fibromyalgia. Redox Rep. 2014;19(4):148-53.
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Mustafa Tuna, Alparslan Yetişgin, Müslüm Toptan, Adnan Kirmit. Evaluation of plasma total antioxidant, total oxidant, thiol-disulphide and optical coherence tomography data in fibromyalgia patients. Ann Clin Anal Med 2024;15(11):768-773
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Evaluation of the relationship between subclinical inflammation markers and ketonuria in hyperemesis gravidarum
Yigit Mert Bayrak, Ramazan Ozyurt, Levent Yaşar
Department of Obstetrics and Gynecology, Gynecology Clinic, Bakırköy Sadi Konuk Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.22251 Received: 2024-05-07 Accepted: 2024-06-12 Published Online: 2024-09-13 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):774-779
Corresponding Author: Ramazan Ozyurt, Department of Obstetrics and Gynecology, Gynecology Clinic, Bakırköy Sadi Konuk Training and Research Hospital, Istanbul, Turkey. E-mail: atasagun02@hotmail.com P: +90 532 748 34 90 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6822-2222
Other Authors ORCID ID: Yiğit Mert Bayrak, https://orcid.org/0009-0001-9185-5391 . Levent Yaşar, https://orcid.org/0000-0002-8679-2699
This study was approved by the Ethics Committee of Bakırköy Sadi Konuk Research and Training Hospital (Date: 2023-09-16, No 398/20-12)
Aim: The study aims to analyze indicators of systemic inflammation such as platelet-lymphocyte ratio, monocyte-lymphocyte ratio and neutrophil-lymphocyte ratio in patients with hyperemesis gravidarum (HEG).
Material and Methods: 130 patients diagnosed with HEG according to the criteria of persistent vomiting, ketonuria, electrolyte abnormalities and acid-base disorder constituted the study group. 134 healthy pregnant women, whose age and gestational weeks were matched, constituted the control group. HEG was diagnosed in patients with ketonuria accompanied by a loss of more than 5 percent of their pre-pregnancy weight and vomiting more than three times a day. Both groups were compared in terms of demographic characteristics, hematological parameters and inflammation markers. The relationship between ketonuria severity and inflammation markers of patients in the HEG group was also analyzed.
Results: The average age of participants was found to be 8.67±5.72. BMI, parity, and weight of patients in the HEG group were found to be significantly lower than those of controls. HB and hematocrit values of the HEG group were found to be significantly higher than controls (p<0.001). NLO values of patients with 1+ ketonuria were significantly lower than those with 3+ ketonuria (p<0.01). PLO values of patients with 3+ ketonuria were significantly higher than those with 1+ and 2+ ketonuria (p=0.005; p=0.013; p<0.05). MLO measurements of cases with 3+ ketonuria were significantly higher than those with 1+ and 2+ ketonuria.
Discussion: The relationship between NLO, MLO, PLO and ketonuria in HEG can be used to monitor the effectiveness of treatment and evaluate the development of complications.
Keywords: Hyperemesis Gravidarum, Inflammation, Ketonuria
Introduction
Hyperemesis gravidarum (HEG) is a pregnancy-specific process characterized by persistent vomiting unrelated to other causes of vomiting in pregnancy, inability to feed, ketonuria, and deterioration in electrolyte and acid-base balance [1]. HEG, which is most common in non-smoking primiparous pregnant women, is the most common reason for hospitalization in the first half of pregnancy [2-4]. Although it varies depending on the population studied and ethnicity, the prevalence of hyperemesis gravidarum varies between 0.3 and 10.8% [1, 2]. Differences in the criteria used for diagnosis are considered to be the cause of different prevalences [2-4]. It has been reported that the incidence increases significantly when mild pregnancy nausea and vomiting that does not cause electrolyte imbalance is considered as HEG [4]. If not monitored and treated appropriately, it can cause morbidity in the mother and her fetus. Although most cases of HEG go into remission with diet and lifestyle changes, one in three patients experience findings that may require hospitalization, antiemetics, liquid electrolyte support and vitamin supplements [2]. Depending on the severity of HEG, changes in laboratory parameters may be in a wide spectrum, ranging from hyponatremia and hypokalemia to alkylosis [5]. It is not surprising to encounter, in rare cases, weight loss, tachycardia, hypotension, skin changes and psychiatric problems [1, 2].
Although the etiology of HEG is mostly attributed to genetic, hormonal and infectious etiologies, in the last decade it has been emphasized that the expression defect of placenta-derived proteins and the increase in placental and systemic inflammation are important in the emergence of the disease [2, 6]. In fact, studies reporting a positive relationship between the severity of ketonuria and inflammatory markers have begun to be published [6-8]. Hematological parameters such as mean platelet volume (MPV), platelet distribution width (PDW), red cell distribution width (RDW), plateletcrit (PCT), platelet-to-lymphocyte ratio (PLO), neutrophil-to-lymphocyte ratio (NLO) and monocyte-to-lymphocyte ratio (MLO) are widely used to show the inflammatory background of many diseases [9]. Detecting the levels of inflammatory markers by ELISA or PCR method is expensive and time-consuming. Inflammatory markers measured with the help of venous blood samples provide a faster, easier and cheaper alternative for early diagnosis of the disease and initiation of treatment. This study was planned to analyze indicators of systemic inflammation such as platelet-lymphocyte ratio, monocyte-lymphocyte ratio and neutrophil-lymphocyte ratio, in addition to mean platelet volume, platelet distribution width, plateletcrit and red cell distribution width of patients diagnosed with HEG. The relationship between inflammatory markers and severity of katonuria was also analyzed.
Material and Methods
This case-controlled thesis study was conducted retrospectively on patients who applied to Bakırköy Sadi Konuk Research and Training Hospital Department of Obstetrics and Gynecology between 2018 and 2023 and were diagnosed with hyperemesis gravidarum. The number of participants was determined with the G*Power (v3.1.9.2) program, taking into account the probability of error (1-β) and having a power of 80%. According to the calculation made taking into account Cohen’s effect size coefficient (d = 0.5), it was decided that there should be at least 96 people in each group, assuming α = 0.01.
Of the total 264 participants, 130 were pregnant women with HEG and 134 were healthy pregnant women without clinical and laboratory findings of HEG. Age, gravida, parity, BMI and laboratory data of the participants in both groups were collected and recorded through the hospital automation system. HEG patients in the study group and healthy pregnant controls were matched in terms of maternal age and gestational age. A combination of different laboratory and demographic criteria was considered for the diagnosis of HEG. HEG was diagnosed in patients with ketonuria accompanied by a loss of more than 5 percent of their pre-pregnancy weight and vomiting more than three times a day. In cases where weight loss was not evident, HEG was diagnosed in the presence of persistent nausea, vomiting, difficulty in feeding, electrolyte imbalance or ketonuria [10]. Both groups were compared in terms of demographic characteristics, hematological parameters and inflammation markers. The relationship between ketonuria severity and inflammation markers of patients in the HEG group was also analyzed.
Patients who were between 6 and 20 weeks of gestation, had a singleton pregnancy, had no systemic disease, and were non-smokers were included in the study. Multiple pregnancies, patients with a history of additional obstetric or systemic diseases, patients with a gestational age less than 6 weeks and older than 20 weeks, patients under 18 years of age and over 40 years of age were not included in the study. WBC, NEU, LYM, HB, HCT, PLT, MPV, PDW, PCT and RDW values of the participants in both groups at the time of HEG diagnosis were collected from their digital files. NLO, PLO, and MLO were calculated by dividing the absolute neutrophil count by the absolute lymphocyte count, the absolute platelet count by the absolute lymphocyte count, and the absolute monocyte count by the absolute lymphocyte count, respectively. The presence and severity of ketonuria in the complete urine analysis performed for the diagnosis of HEG (1+, 2+ and 3+ indicate increased severity in ketonuria) were recorded.
Statistical Analysis
SPSS 2027 program was used for data analysis. Quantitative variables were presented as mean, standard deviation, median, Q1 and Q3, while qualitative variables were presented as frequency and percentage. Whether the data showed normal distribution was determined by Shapiro Wilks test and Box Plot graphics. Student’s t test or Oneway Anova test was used to evaluate normal variables. The group causing the difference was determined by Bonferroni correction. Mann Whitney U test or Kruskal Wallis test was used to evaluate abnormally distributed variables, and Dunn test was used to determine the group causing the difference. Chi-Square test or Fisher’s Freeman Halton test was used to compare qualitative data. Pearson or Spearman’s correlation was used to analyze the relationships between variables. P<0.05 was considered significant within the 95% confidence interval.
Ethical Approval
This study was approved by the Ethics Committee of Bakırköy Sadi Konuk Research and Training Hospital (Date: 2023-09-16, No:2023-20-12). Data collection started after receiving approval from the ethics committee approval.
Results
Table 1 shows the demographic characteristics of both groups in detail. Of the total 264 participants, 130 (49.2%) were HEG and 134 (50.8%) were healthy controls. The average age of all participants was found to be 8.67±5.72. BMI, parity, and weight of patients in the HEG group were found to be significantly lower than those of healthy patients (p<0.001, p<0.003 and p<0.001, respectively).
Table 2 shows the hematological and cytokine profiles of both groups in detail. HB and hematocrit values of the HEG group were found to be significantly higher than healthy controls (p<0.001). The PDW value of the control group was significantly lower than HEG (p<0.01). The PDW value of the control group was significantly lower than HEG (p<0.01). The MPV values of the participants in the HEG group were found to be significantly lower than the healthy group (p<0.01). Urine density was found to be significantly higher in the HEG group compared to controls (p<0.01).
Table 3 details the distribution of laboratory parameters and inflammation markers according to the severity of ketonuria. NEU value of patients with 1+ ketonuria is significantly lower than patients with 3+ ketonuria (p<0.05). The LYM value of patients with 1+ ketonuria was significantly higher than that of patients with 3+ ketonuria (p<0.05). The RDW value of patients with 2+ ketonuria was found to be significantly higher than those with 3+ ketonuria (p<0.05). NLO values of patients with 1+ ketonuria were significantly lower than those with 3+ ketonuria (p<0.01). PLO values of patients with 3+ ketonuria were significantly higher than those with 1+ ketonuria and 2+ ketonuria (p=0.005; p=0.013; p<0.05). MLO measurements of cases with 3+ ketonuria were recorded significantly higher than those with 1+ ketonuria and 2+ ketonuria (p<0.003 and p<0.014, respectively).
Discussion
Hyperemesis gravidarum is a pregnancy-specific disease that begins in the 6th week of pregnancy, with symptoms peaking at the 13th week of pregnancy and decreasing in severity after the 20th week of pregnancy. Many studies report that HEG is one of the most common causes of hospitalization in the early weeks of pregnancy [2-4]. Subclinical inflammation describes the non-infectious increase of cytokines that play a critical role in maintaining intracellular redox balance and protein synthesis. Chronic low-grade subclinical inflammation causes cell damage and worsening of symptoms through a mechanism called inflammatory aging [11]. The relationship between ketonuria and proinflammation in HEG has been evaluated in some studies [12, 13]. Our study, unlike others, is privileged in that it performs subgroup analysis of changes in a larger number of subclinical inflammation markers according to the severity of ketonuria. PCT, MPV, PDW, RDW, MLO, PLO and NLO were used as subclinical inflammation markers. Additionally, the relationship between HB, HCT, WBC, MON, NEU and PLT values and ketonuria severity was analyzed in both groups.
No significant difference was detected in age, height, gestational age and gravity between the two groups. However, parity, BMI, and weight of the HEG group were found to be significantly lower than the control group. The heterogeneity of the groups can be attributed to the retrospective nature of the study. The lower BMI and weight of the HEG group than the controls may be due to feeding difficulty and persistent vomiting. Consistent with our results, in a study comparing HEG and healthy pregnant women, a significant decrease was found in the BMI values of those with HEG during pregnancy compared to the healthy group, although pre-pregnancy BMI values were similar [14]. Similarly, we found that HB and hematocrit values of patients diagnosed with HEG were significantly higher than healthy controls. It is thought that the decrease in HB and hematocrit in HEG patients develops as a result of hemoconcentration due to persistent vomiting and insufficient fluid intake [15]. No significant change was detected in the number of LYM and RDW between the groups. RDW reflects the change in erythrocyte volume, also referred to as anisocytosis. The study results are heterogeneous in terms of these two parameters [16]. High RDW is thought to be related to increased inflammation and oxidative stress [17]. PCT is obtained by multiplying the platelet count by MPV and dividing by 10 thousand [18]. PCT may be high, low or normal in patients with HEG [19]. The fact that the groups were similar in terms of PCT suggests that there is no significant change in the levels of this marker in the early stages of HEG. The similarity of WBC, PLT, NEU and MON between the two groups can be attributed to the fact that demographic and medical parameters such as age, gender, smoking, stress and medications affect the blood levels of these markers [20, 21].
The fact that no difference was found between the NLO, PLO and MLO measurements of the groups is compatible with some studies in the literature and is inconsistent with others [20, 21]. The real change in these markers with a single measurement may not be reflected in the clinic. More clear results can be obtained with multiple measurements at different stages of HEG. Ketone measurements in urine have been reported as diagnostic criteria in approximately 60% of clinical studies in the diagnosis of HEG. The most well-known ketone bodies that occur when fats are used for energy are acetoacetate and beta-hydroxybutyric acid. Ketonuria is a good parameter to understand the metabolic consequences of fluid loss and starvation [18-20]. We did not detect a relationship between ketonuria and HB, hematocrit, PLT and WBC. Since HB, hematocrit, WBC and PLT values are affected by many factors, a clear correlation between them and the severity of ketonuria may not be detected. NLO measurements of cases with 1+ ketonuria are significantly lower than those with 3+ ketonuria. NLO is calculated by dividing neutrophil and lymphocyte counts. It has been reported that the NLO value is higher in pregnant women diagnosed with HEG than in controls [19, 21]. Similarly, the calculated PLO and MLO of cases with 3+ ketonuria is significantly higher than those with 1+ and 2+ ketonuria. Many HEG studies support the correlation between ketonuria severity and PLO and MLO [18, 19]. As a result, the relationship between NLO, MLO and PLO and ketonuria in HEG can be used to monitor the effectiveness of treatment and evaluate the development of complications.
The study has some limitations. Although a sufficient number of cases were studied, the retrospective nature of the study is an important limitation. Although subclinical inflammation markers such as MLO, PLO and NLO are associated with the severity of ketonuria, it should not be forgotten that these markers can be affected by many factors related to the patient. These limitations can be overcome with a study design that analyzes the changes of subclinical inflammation markers before, during and after pregnancy.
Conclusion
Evaluation of ketonuria and subclinical inflammation markers during the initial examination of patients diagnosed with hyperemesis gravidarum is important for the management of the disease and metabolic control. Monitoring of subclinical inflammation markers should be done more frequently in HEG patients with ketonuria, as urine ketone values vary depending on the patient’s metabolic state. Close monitoring of these markers will help the clinician in assessing the severity of the disease along with ketonuria and determining the response to treatment.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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Yigit Mert Bayrak, Ramazan Ozyurt, Levent Yaşar. Evaluation of the relationship between subclinical inflammation markers and ketonuria in hyperemesis gravidarum. Ann Clin Anal Med 2024;15(11):774-779
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Comparison of open diverticulectomy and endoscopic diverticulum fulguration in patients with acquired symptomatic bladder diverticula
Ferhat Yakup Suçeken, Murat Beyatlı, Ali Selim Durmaz, Ömer Faruk Örnek, Nurullah Mustafa Şişik, Metin Mod, Hakan Karaca, Eyüp Veli Küçük
Department of Urology, Umraniye Training and Research Hospital, Istanbul, Turkiye
DOI: 10.4328/ACAM.22288 Received: 2024-05-30 Accepted: 2024-08-26 Published Online: 2024-017 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):780-783
Corresponding Author: Ferhat Yakup Suçeken, Department of Urology, Umraniye Training and Research Hospital, Istanbul, Turkiye. E-mail: ykpsckn@gmail.com P: +90 505 288 49 76 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7605-4353
Other Authors ORCID ID: Murat Beyatlı, https://orcid.org/0000-0003-0945-0051 . Ali Selim Durmaz, https://orcid.org/0009-0006-7542-9751 . Ömer Faruk Örnek, https://orcid.org/0009-0008-1049-7424 . Nurullah Mustafa Şişik, https://orcid.org/0009-0009-6889-6601 . Metin Mod, https://orcid.org/0000-0002-5155-4762 . Hakan Karaca, https://orcid.org/0000-0003-4592-9369 . Eyüp Veli Küçük, https://orcid.org/0000-0003-1744-8242
This study was approved by the Ethics Committee of Umraniye Training and Research Hospital (Date: 11-05-2023, No: 158)
Aim: In this study, we aimed to compare patients with acquired symptomatic bladder diverticula who underwent open diverticulectomy or endoscopic diverticulum fulguration.
Material and Methods: The data of patients between January 2018 and January 2023 were retrospectively reviewed. Demographic data, laboratory parameters, and perioperative and postoperative data were noted. International Prostate Symptom Score (IPSS) and Quality of Life (QOL) scores were analyzed. Patients who underwent open diverticulectomy were classified as Group 1 and patients who underwent endoscopic diverticulectomy were classified as Group 2.
Results: A total of 15 patients were included in the study. The operation time was 67 ± 21.2 minutes in Group 1 and 22.3 ± 10.1 minutes in Group 2, with a significantly shorter operation time in Group 2. (p= 0.001) The mean hospital stay was 3.1 ± 1.2 days in Group 1 and 1.1 ± 0.3 days in Group 2, with a significantly shorter hospital stay in Group 2. (p=0.01) The rate of symptom improvement was similar. There was a significant decrease in PMR measurements in both groups in the postoperative period. QoL evaluation showed a significant increase in both groups. The complication rates were similar.
Discussion: In patients with symptomatic bladder diverticula, endoscopic fulguration provides similar efficacy and safety to open surgery. It can be preferred in comorbid patients with high anesthesia risk due to shorter operations and hospital stays.
Keywords: Open Diverticulectomy, Endoscopic Fulguration, Bladder Diverticula
Introduction
Bladder diverticula are divided into congenital and acquired. [1] Congenital diverticula are usually seen in childhood and involve all layers of the bladder. [2] Acquired bladder diverticula are caused by herniation of the bladder mucosa through weakened detrusor muscles. This is often caused by conditions such as benign prostatic hyperplasia (BPH), bladder neck stenosis, and urethral strictures that cause outlet obstruction. [2] Treatment is indicated in patients who are symptomatic or develop complications.
Open, laparoscopic, and robotic surgical methods have been described as treatment options. [2] Especially in patients with more comorbid conditions and high anesthesia risk, in the presence of diverticula below 4 cm, the endoscopic fulguration technique described by Orandi et al. [3] There are studies indicating that this technique is also reliable in larger diverticulum sizes. [2, 4, 5]
In this study, we aimed to compare patients with acquired symptomatic bladder diverticula who underwent open diverticulectomy or endoscopic diverticulum fulguration.
Material and Methods
The data of patients who underwent open diverticulectomy or trans-urethral diverticulum neck excision for symptomatic bladder diverticulum between January 2018 and January 2023 were retrospectively reviewed. All operations were performed by surgeons who completed the learning curve at Ümraniye Training and Research Hospital.
Patients older than 18 years with symptomatic acquired bladder diverticulum were included in the study. Patients with previous open bladder operations, a history of bladder tumor, neurogenic dysfunction, a history of pelvic radiotherapy, and patients with missing data were excluded.
Demographic data, ASA scores, and Charlson Comorbidity Index scores were noted. Laboratory parameters such as creatinine and PSA were analyzed. International Prostate Symptom Score (IPSS) and Quality of Life scores were analyzed. The quality of life questionnaire was evaluated with the SF-36 form. Diverticulum sizes, prostate volumes, uroflowmeter parameters, and follow-up times were noted. Perioperative and postoperative operation times, complications, hospital stay, and catheterization times were noted. In the endoscopic method, surgical success was defined as at least 80% reduction in diverticulum size at the 3rd month of evaluation. Complications were classified according to the Clavien-Dindo Classification.
Patients who underwent open diverticulectomy were classified as Group 1 and patients who underwent endoscopic diverticulectomy were classified as Group 2 and the 2 groups were compared.
Surgical Technique
Endoscopic Incision
The bladder was accessed transurethrally with the help of a 26 Fr resectoscope. The diverticular mucosa was completely fulgured with the help of a rollerball electrode. Afterward, the diverticulum mouth was incised with plasma vaporization. At the end of the operation, a 3-way catheter was inserted and continuous irrigation was applied.
Open Surgical Technique
The retzius cavity was entered by crossing the folds with the Phannelstein incision. The cystoscopy was performed transurethrally and white light was used inside the diverticulum. In this way, the diverticulum was identified through the incision. Suspension sutures were placed and the diverticulum was incised from the intact bladder tissue. The bladder was then closed in 2 layers and the layers were closed by placing a drain in the lumen. Continuous irrigation with a 3-way catheter was applied postoperatively.
Postoperative Follow-up
The duration of catheterization was determined according to the surgeon’s preference. In both groups, cefazolin 1000 mg was administered as antibiotic prophylaxis 30 min before the start of surgery. Operative success was evaluated by CT cystography 3 months after the procedure. In addition, uroflowmeter and IPSS values were measured.
Statistical Analysis
Whether the numerical data showed normal distribution was evaluated by the Kolmogorov-Smirnov test. Normally distributed numerical data were compared with the Student T test. Chi-square or Fisher’s exact test was used to compare categorical variables when appropriate. A paired samples t-test was used for in-group before and after comparisons. A significant p-value < 0.05 was accepted. R 3.3.2 software was used for the applications.
Ethical Approval
This study was approved by the Ethics Committee of Umraniye Training and Research Hospital (Date: 11-05-2023, No: 158).
Results
After the application of inclusion and exclusion criteria, a total of 15 patients were included in the study, 5 (33.3%) in Group 1 and 10 (66.6%) in Group 2. The mean age of the patients included in the study was 64.1 ± 8.1 years. There was no significant difference between the two groups in age, BMI, and Charlson Coordination Index scores. ASA scores were significantly higher in Group 2.
The rates of BPH were similar between the two groups. Group 1 had a significantly higher rate of previous trans vesical prostatectomy and Group 2 had a significantly higher rate of previous transurethral prostatectomy. There was no significant difference between bladder stone and diverticulum stone rates. Preoperative serum creatinine and PSA levels were similar. The operation time was 67 ± 21.2 minutes in Group 1 and 22.3 ± 10.1 minutes in Group 2, with a significantly shorter operation time in Group 2. (p= 0.001) The catheterization time was 13.1 ± 1.1 days in Group 1 and 7.4 ± 2.2 days in Group 2, with a significantly shorter catheterization time in Group 2. (p=0.03) The mean hospital stay was 3.1 ± 1.2 days in Group 1 and 1.1 ± 0.3 days in Group 2, with a significantly shorter hospital stay in Group 2. (p=0.01) The mean follow-up period was 23.9 ± 12.8 months, with no significant difference between the two groups. When the rate of symptom improvement during the follow-up period was evaluated, 86.6% of the patients improved in total, and no significant difference was observed between the two groups. In group 2, symptoms persisted in 2 patients (20%) (Table 1).
When the functional results were evaluated, a significant decrease in IPSS values before and after treatment was detected in both groups. IPSS scores improved at a similar rate between the two groups. Significant improvements in Qmax values were detected in both groups after treatment. Improvement rates were similar between the two groups. Although there was a significant increase in bladder capacity in both groups in the postoperative period, there was no difference between the groups. There was a significant decrease in PMR measurements in both groups in the postoperative period, but there was no difference between the groups. Quality of life evaluation showed a significant increase in both groups. This increase was similar between the groups. Diverticulum dimensions showed a significant decrease in the postoperative period in both groups, but this rate was higher in Group 1. (Table 2)
Grade 1 and Grade 2 complications were detected in all patients. Erythrocyte Replacement Therapy was needed in 1 patient (20%) in Group 1 and hematuria was detected in 2 patients (20%) in Group 2. There was no difference in complication rates between the groups (Table 3).
Discussion
Acquired bladder diverticula develop when the mucosa protrudes from the weakened bladder tissue [6]. In patients with lower urinary tract obstruction, high pressure due to detrusor contraction during micturition and chronicization of this condition is involved in the etiology of acquired bladder diverticula. [6] The diverticulum wall contains mucosa, subepithelial connective tissue, very rare detrusor muscle fibers, and adventitial tissues from inside to outside [7]. Causes of intravesical obstruction such as anterior and posterior urethral valves, urethral strictures, BPH, neurogenic dysfunction, and detrusor sphincter dyssynergia can lead to this condition [8]. Since they often develop secondary to obstruction, they are known as diseases of advanced age.
Acquired bladder diverticula are often asymptomatic and are usually diagnosed on routine abdominal ultrasonography [1]. In the presence of larger diverticula, lower urinary tract infections, voiding disorders, pelvic pain, and hematuria may be detected [9].
Large diverticula can cause post-mictional residue, bladder stones, urinary tract infections, and local compression [6]. Surgical treatment aims to prevent these symptoms and complications [2]. Surgical technique may vary according to diverticulum size, location, presence of additional anomalies, and surgeon’s preference [1].
The first surgical method in the treatment of bladder diverticulum was described by Alexander in 1884 and Czerni in 1897. [10] The technique was later developed by Lerche [11]. The transvesical technique was described by Young in 1906, the extravesical or combined technique by Barnes in 1939, then open surgery, endoscopic fulguration [1, 4]. Today, open, endoscopic, laparoscopic, and robot-assisted systems are successfully applied [1]. Laparoscopic and robotic techniques have replaced open surgery in many centers [12, 14]. Endoscopic treatments are generally reported for smaller-sized diverticula [3, 15, 16]. However, as a result of developments in endoscopic methods, studies are reporting that diverticula between 20 ml and 700 ml are treated endoscopically [17].
There are numerous case series on endoscopic management of bladder diverticula. Transurethral fulguration, first described by Orandi et al. in a series of 17 patients, resulted in complete resolution in 5 patients and volume reduction in 9 patients [3]. Similarly, Clayman et al. reported complete resolution in 5 patients and volume reduction in 1 patient in a study of 6 patients [16]. Yamaguchi et al. reported complete resolution in 26 of 31 patients in a study of 31 patients.[18] Martov et al. reported 95% success rate in a series of 29 patients in which the diverticulum neck was endoscopically incised [17]. In a study conducted by Rippa et al. in a series of 21 patients, failure of the procedure was reported in only 1 patient [19]. In a study conducted by Pacella et al [2]. laparoscopic and endoscopic methods were compared. Although both methods were found to be safe and effective, endoscopic methods were reported to have a shorter operation time and success in 75% of cases. The fact that endoscopic methods can be performed under spinal anesthesia is also an advantage for comorbid patients [2]. It is also reported to have a shorter learning curve compared to open/laparoscopic and robotic surgeries [2].
It is also reported to have a shorter learning curve compared to open/laparoscopic and robotic surgeries [2]. In addition, in case of failure of the procedure, subsequent open/laparoscopic or robotic surgeries are not affected. Endoscopic methods have become a good alternative in diverticulum surgery due to successful results and better functional outcomes [20]. In our study, it was found that although the group that underwent endoscopy was more comorbid, complication and success rates were similar. In addition, shorter operation time, catheterization time, and hospital stay were found in the endoscopic method.
Limitation
Our study has some limitations. The small number of patients and the retrospective nature of the study are the main limitations of the study. The fact that the group that underwent endoscopy was more comorbid suggests heterogeneous groups, but the fact that the results were similar despite this indicates the reliability of endoscopic methods. More large series, randomized controlled studies are needed in this regard.
Conclusion
In patients with symptomatic bladder diverticula, endoscopic fulguration provides similar efficacy and safety to open surgery. It can be preferred in comorbid patients with high anesthesia risk due to shorter operations and hospital stays.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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Download attachments: 10.4328.ACAM.22288.pdf
Ferhat Yakup Suçeken, Murat Beyatlı, Ali Selim Durmaz, Ömer Faruk Örnek Nurullah Mustafa Şişik, Metin Mod, Hakan Karaca, Eyüp Veli Küçük. Comparison of open diverticulectomy and endoscopic diverticulum fulguration in patients with acquired symptomatic bladder diverticula. Ann Clin Anal Med 2024;15(11):780-783
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Can biological markers predict mortality in bowel ischemia
Adem Senturk 1, Alp Omer Canturk 2, Fuldem Mutlu 3
1 Department of Surgical Oncology, Sakarya Training and Research Hospital, 2 Department of General Surgery, Sakarya Training and Research Hospital, 3 Department of Radiology, Faculty of Medicine, Sakarya University, Sakarya, Turkiye
DOI: 10.4328/ACAM.22308 Received: 2024-06-15 Accepted: 2024-08-12 Published Online: 2024-08-23 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):784-788
Corresponding Author: Adem Senturk, Department of Surgical Oncology, Sakarya Training and Research Hospital, Sakarya, Turkiye. E-mail: dr.adem.senturk@gmail.com P: +90 536 029 07 24 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7626-4649
Other Authors ORCID ID: Alp Omer Canturk, https://orcid.org/0000-0003-3641-7628 . Fuldem Mutlu, https://orcid.org/0000-0001-7761-2417
This study was approved by the Ethics Committee of Sakarya University (Date: 2023-07-28, No: 245)
Aim: High levels of fibrinogen and low levels of albumin are associated with ischemic vascular diseases. This study aims to investigate whether the levels of serum fibrinogen and albumin, FAO, and prognostic nutritional index (PNI) effectively predict prognosis in acute mesenteric ischemia.
Material and Methods: Patients treated in our clinic with the diagnosis of Acute mesenteric ischemia (AMI) between 2013 and 2023 were evaluated for inclusion. Patients were divided into two groups: those who were alive after the first month (group 1) and those who died within the first month (group 2). The investigated parameters were statistically compared between these groups.
Results: We included 39 patients in this study. Twenty-one of the patients (53.8%) were alive one month after the surgery (group 1), whereas 18 patients (46.2%) died (group 2). The difference in the mean ages of patients in both groups was not statistically significant (74.6±9.2 and 69.4±10.6, respectively; p=0.114). Group 2 had higher fibrinogen levels compared with group 1 (524.0±165.7 mg/dL vs. 427.8±114.0 mg/dL; p=0.039). Albumin levels were similar between the two groups (3.0±0.6 g/dL vs. 2.8±0.5 g/dL; p=0.179). The mean FAR value was significantly higher in group 2 (198.5±76.9 vs. 149.8±56.9; p=0.029). FAR in 71.8% of them with the optimal cut-off value >157.6 (AUC= 0.688, p= 0.033). PNI was not successful in predicting mortality (AUC=0.605, p=0.189)
Discussion: The present study proposed that the FAO could be a new and valuable prognostic marker in patients with AMI, unlike PNI.
Keywords: Far, Fibrinogen, Albumin, Ami, Prognosis
Introduction
Acute mesenteric ischemia AMI represents a critical vascular condition occurring when blood supply to the intestine is compromised, resulting in tissue death due to ischemia caused by arterial or venous blockage, or constriction of mesenteric vessels, accompanied by subsequent tissue damage during blood flow restoration [1]. The frequency of its occurrence rises with advancing age, and prior studies have documented that the average age of onset falls toward the end of the seventh decade of life [1- 6]. Surgery for mesenteric ischemia accounts for 0.1-0.2% of acute surgical interventions in general hospital practice [5]. It represents approximately 1 patient out of every 1000 patients hospitalized with acute abdomen [4, 6]. The total occurrence rate of AMI is documented as 0.63 per 100,000 individuals in Europe, with an equal distribution between females and males [1, 4]. A recent Swedish study reported an incidence rate of 13 per 100,000 person-years over a 10-year period [7].
Common symptoms comprise abrupt onset of diffuse abdominal pain, accompanied by nausea, vomiting, diarrhea, and rectal bleeding. Despite advancements in diagnostic techniques and treatment options, mortality rates remain elevated [6] Early diagnosis relies heavily on clinical suspicion. Suspected cases should undergo evaluation with computed tomography angiography (CTA) for accurate diagnosis [1, 2, 4, 6].
Various biomarkers, including white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), citrulline, and D-dimer, have been assessed for early detection of AMI. Nevertheless, there are currently no universally accepted biomarkers for such cases [8].
Elevated fibrinogen levels and decreased albumin levels have been linked to the systemic disorders. The fibrinogen-to-albumin ratio (FAR), a recently proposed parameter, has been investigated for its diagnostic and prognostic utility in various conditions characterized by inflammation and pro-coagulation, including coronary artery disease, cerebrovascular stroke, retinal venous occlusion, and cancers [9]. There are no studies investigating the predictive value of FAR in AMI prognosis. The aim of this study is to evaluate the predictive value of preoperative albumin, fibrinogen, and FAR levels in the prognosis of AMI.
Material and Methods
The records of the patients who underwent surgery for AMI between 2014 and 2023 were analyzed retrospectively. Ethical approval was obtained from the Ethics Committee of the University. We collected the patient’s data from the database of the general surgery department of our third-level hospital, which is the sole reference center for patients of acute mesenteric ischemia in our city. We derived the radiology, laboratory, clinical, and therapeutic data. Patients without laboratory data regarding the albumin and fibrinogen levels during the initial 48 hours of abdominal complaints were excluded.
AMI was identified by visualizing halted blood circulation on Computed Tomography Angiography or digital subtraction angiography (DSA), or by detecting ischemic alterations in the intestinal wall during surgical interventions.
The FAR was recorded within the first 48 hours after the onset of abdominal complaints.
Demographics, primary diagnosis, medical history, laboratory results, imaging findings, and examination findings of the patients were obtained from the records of our hospital. Hemogram, FAR biochemistry, CRP, prothrombin time (PT), and the international normalized ratio (INR), which were tested concurrently within the first 48 hours after symptom onset were derived.
The population of the study is divided into two groups regarding the outcome described as exitus (death within the month without any other defined etiology) or alive (living at the end of the first month). In addition, the study population was categorized according to the extent of applied surgical procedure as patients with small intestine resection (SIR group) and patients with small intestine and colon resection (SICR group). The measured parameters were compared between these subgroups.
Statistical analysis was performed by using the Statistics Open For All package – SOFA stat (released with open source AGPL3 license 2009–2014; Paton Simpson and Associates Ltd, New Zealand). ROC curve analyses were done with MedCalc version 20.027 statistical software program (Ostend, Belgium). Descriptive statistics were expressed as mean±standard deviation (for normally distributed data), median and minimum–maximum (for not normally distributed data) or number of cases and percentage (%) (for Categorical variables). Normally distributed homogeneous data were compared with the Student’s T-test. The data without normal distribution or not homogeneous were compared with the Mann-Whitney U test. Pearson linear correlation test or Spearman’s Correlation Analysis was used for the correlation analysis. Less than 0.05 P values were considered significant. The receiver operating characteristic (ROC) curve was used to determine the predictive value of FAR according to the outcome and extent of ischemia. Youden J index was used to determine cut-off values.
Ethical Approval
This study was approved by the Ethics Committee of Sakarya University, Faculty of Medicine (Date: 2023-07-28, No:245).
Results
In total, 39 patients with AMI whose medical records were accessed from the archives of our hospital were included in this study. Thirty-three of them (84.6%) had arterial occlusive mesenteric ischemia, five of them (12.8%) had mesenteric venous thrombosis whereas one of them (2.6%) had a non-occlusive mesenteric ischemia. Eleven of the patients (28.2%) were treated medically after thrombectomy with DSA, one of the patients (2.6%) were treated with surgical thrombectomy without intestinal resection, 26 of the patients (66.7%) were treated with surgical resection, and one of the patients (2.6%) died just before the operation. Among the surgically treated patients, intestinal resection was applied in 11 of them with anastomosis, and in 13 of them with ostomies, and 2 of them who had total intestinal ischemia died during the surgery.
Twenty-one of the patients (53.8%) were alive one month after the surgery (group 1) whereas 18 patients (46.2%) died (group 2) two of them died during the operation and one of them died just before the surgery. The ischemia involved the
small intestine insole (small intestine ischemia- SII- group) in 29 (74.4%) of the patients, whereas the colon was also affected in 9 (23.1%) of the patients (small intestine and colon ischemia – SICI- group). In one patient (2.5%), the right colon and cecum were involved insole.
The mean ages of the surviving and dead patients were similar (74.6±9.2 and 69.4±10.6, respectively; p=0.114). Distributions of gender and laboratory parameters regarding inflammation were similar between the two groups. (Table 1) Albumin levels were similar between two groups (3.0±0.6 gr/dL vs. 2.8±0.5 gr/dL; p=0.179). Group 2 had higher fibrinogen levels compared with group 1 (524.0±165.7 mg/dL vs. 427.8±114.0 mg/dL; p=0.039). The mean FAR value was significantly higher in group 2 (198.5±76.9 vs. 149.8±56.9; p=0.029).
The mean ages of SII (73.4±8.9) and SICI (69.7±13.3) were similar. (p=0.139). Distributions of gender and laboratory parameters regarding inflammation were shown in Table 2. SII and SICI groups had similar fibrinogen, albumin and FAR values (p >0.05 for all comparisons)
There was an inverse linear correlation between the serum fibrinogen and albumin levels in the study population (p=0.027). (Figure 1) ROC curves were plotted for albumin, FAR, and fibrinogen to identify non-survivors. (Figure 2) We also calculated the specificity, sensitivity, accuracy, negative likelihood ratio (−LR), and positive likelihood ratio (+LR) for optimal cut-off values in predicting mortality within one month (Table 3). Fibrinogen levels predicted the mortality in 66.7% of the patients accurately with the optimal cut-off value >476 mg/dL (AUC= 0.677, p= 0.041), albumin in 64.7% of them with the optimal cut-off value ≤3.1 g/dL (AUC= 0.630, p= 0.159) and FAR in 71.8% of them with the optimal cut-off value >157.6 (AUC= 0.688, p= 0.033). PNI was not successful in predicting mortality (AUC=0.605, p=0.189) (Figure 3)
Discussion
AMI is associated with high morbidity and mortality. Its etiology is primarily linked to in situ thrombosis in approximately 60% of patients. However, embolism due to atrial fibrillation is the underlying cause in 30% of patients and non-occlusive mesenteric ischemia in 10%. [10] Despite the increasing number of cases due to the aging population, diagnosis remains challenging with initial physical examination and diagnostic imaging [11]. In elderly patients presenting with sudden abdominal pain accompanied by minimal initial physical findings as well as vomiting and bloody diarrhea, especially if there is a history of atrial fibrillation, or metallic valve implantation, AMI should be suspected. Following the exclusion of other causes of abdominal pain, most patients undergo a computerized tomographic scan (CT) to visualize the anatomy of the mesenteric vessels. Traditional treatment has typically involved open surgical revascularization, which may include procedures such as embolectomy, bypass, and endarterectomy [12, 13]. Despite significant advancements in surgical and
radiological techniques, the mortality rate associated with AMI remains high [8]. In our study population, the mortality rate was 46.2%. Our research focused on assessing the predictive value
of traditional inflammatory parameters and a novel parameter, FAR, in patients with acute mesenteric occlusion. Our findings
indicate that platelet, neutrophil, lymphocyte, white blood cell, hemoglobin, CRP, albumin counts, and NLR are not sensitive indicators for predicting the extent of ischemia and mortality. However, we observed that fibrinogen and FAR values may be valuable predictors of mortality.There are few studies in the literature investigating the role of serum biomarkers in predicting AMI prognosis. In a recent study by Wu and colleagues, they examined 77 patients with AMI who underwent laparotomy [14]. In their study, they reported a 30-day postoperative mortality rate of 29.9%. Multivariate analysis revealed that time from admission to surgery, platelet count and arterial mesenteric occlusion were independent predictors of 30-day mortality after exploratory laparotomy. However, other traditional laboratory findings, such as elevated WBC, serum lactate level or CRP levels, are reported to have limited contribution in both diagnosing acute mesenteric occlusion and predicting prognosis [15]. In an animal study conducted by Ozcay and colleagues, it was observed that both partial and diffuse AMI resulted in a decrease in blood glucose levels, along with increases in AST, LDH, and fibrinogen levels in rats. However, the changes noted in ALT, CRP, BUN, and C3 levels were not statistically significant [16]. Our findings indicate that there were no significant differences in the levels of WBC, ALT, and CRP between patients who died and those who survived. However, the fibrinogen level was notably higher in the group of patients who died..
Albumin inhibits platelet aggregation and activation and plays a crucial role as a mediator for platelet-induced vasoconstriction [17]. In in vitro studies using human fibrinogen preparation, fibrinogen-induced platelet aggregation was reversed by adding human albumin. Decreases in serum albumin may elevate the viscosity of blood and impair endothelial function by increasing free lysophosphatidylcholine concentrations [18]. Some studies demonstrated that hypoalbuminemia increases morbidity and mortality in cardiovascular disease, cancer, and other conditions [19]. Serum albumin levels have been proposed to have predictive value in the occurrence and prognosis of vascular occlusions, such as acute myocardial infarction [19] Serum albumin levels have been proposed to have predictive value in the occurrence and prognosis of vascular occlusions, such as acute myocardial infarction [20]. Although the relationship between elevated fibrinogen levels, hypoalbuminemia, and coronary artery disease was investigated in many studies, to our knowledge, none have addressed patients with AMI [8]. In our study, serum albumin levels were not associated with prognosis or the extent of ischemia. However, significantly high FAR values and fibrinogen levels have existed in patients who died within one month after surgery compared to survivors.
The association between serum CRP levels and the prognosis of patients with vascular accidents remains controversial. Winbeck and colleagues reported that elevated levels of CRP measured 12-24 hours after the onset of symptoms, rather than within the first 12 hours, in patients with first ischemic cerebrovascular stroke were associated with an unfavorable outcome and an increased recurrent cerebrovascular and cardiovascular events incidence [21].
Di Napoli et al. reported that CRP predicted the risk of ischemic stroke and that CRP levels at discharge were more closely associated with later outcomes [22]. In another report, Di Napoli and colleagues found that elevated serum CRP levels were more closely associated with new cardiovascular events risk after the first ischemic stroke compared to D-dimer and fibrinogen levels [23]. On the other hand, in a population-based study, Froyshow and colleagues found that fibrinogen and IL-6 were independent predictors of mortality in long-term stroke survivors, while elevated hs-CRP predicted mortality in stroke-free individuals [24].
In a recent report, Destek and colleagues found that CRP level could be used effectively preoperatively to diagnose AMI and to determine its clinical course. They also reported that NLR, D-dimer, L-lactate, and leukocyte levels were markers with no predictive value in the diagnosis of all AMI subtypes. We found that there were not any significant differences in terms of initial CRP and NLR levels between survived and non-survived patients within one month revealing that they are not valuable parameters in the prediction of mortality in patients of acute mesenteric ischaemia.
The previous reports showed that the D-dimer, one of the protein fragments produced during the degradation of fibrinogen, had a high sensitivity in the patients with acute mesenteric ischemia, although it did not get a satisfactory specificity [5]. Recently, Li and colleagues reported that fibrinogen levels in patients who developed necrosis due to strangulated intestinal obstruction were significantly higher than in patients in whom only ischemia was present without necrosis and in patients with intestinal obstruction without ischemia or necrosis [25]. As the occlusion of mesenteric vessels causes ischemia in intestinal tissues, the fibrinogen levels are expected to increase in these patients also. In this study, we aimed to determine the possible values of fibrinogen, albumin, and FAR in predicting the prognosis of acute mesenteric ischemia. Our results revealed that fibrinogen and FAR values were significantly higher in our patients who died within one month after the surgery than those who survived. Fibrinogen levels predicted mortality accurately in 66.7% of the patients within one month, albumin in 64.7% of them, and FAR in 71.8% of them.
Limitation
Our study has some limitations. One of them is the limited number of patients with venous occlusion, hampering the comparative statistics between the arterial and venous occlusion groups. Secondly, post-operative FAR values could not be evaluated as the fibrinogen and/or albumin measurements after the surgery were unavailable in some patients, and the time period between the surgery and the taken of serum specimens could not be standardized in others having postoperative fibrinogen and albumin measurements. Lack of lengths of ischemic bowel segments and D-dimer measurements could also be evaluated as other limitations.
Conclusion
In conclusion, we researched the possible predictive values of fibrinogen, albumin, and FAR, a new rational parameter of inflammation, in the prognosis of patients with AMI unlike PNI, and our results revealed that fibrinogen, which is widely available in emergency wards, and FAR could be valuable prognostic markers in these cases
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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10. Park WM, Gloviczki P, Cherry KJ, Hallett JW, Bower TC, Panneton JM, et al. Noel AA. Contemporary management of AMI: factors associated with survival. J Vasc Surg. 2002;35(3):445–52.
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14. Wu W, Yang L, Zhou Z. Clinical features and factors affecting postoperative mortality for obstructive AMI in China: A hospital- based survey. Vasc Health Risk Manag. 2020;16(1):479-487.
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17. van de Wouw J, Joles JA. Albumin is an interface between blood plasma and cell membrane, and not just a sponge. Clin Kidney J. 2021;15(4):624-634.
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Association of naples score with syntax score in patients with non-ST-segment elevation myocardial infarction
Can Özkan 1, Yücel Kanal 2
1 Department of Cardiology, Bursa City Hospital, Bursa, 2 Department of Cardiology, Sivas Cumhuiyet Universty, Sivas, Turkiye
DOI: 10.4328/ACAM.22326 Received: 2024-07-06 Accepted: 2024-08-12 Published Online: 2024-10-06 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):789-793
Corresponding Author: Can Özkan, Department of Cardiology, Bursa City Hospital, Bursa, Turkiye. E-mail: canozzkan@hotmail.com P: +90 544 454 03 90 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6255-711X
Other Authors ORCID ID: Yücel Kanal, https://orcid.org/0000-0003-0934-0266
This study was approved by the Ethics Committee of Bursa City Hospital (Date: 2024-05-29, No: 2024-9/7)
Aim: This retrospective observational study aimed to investigate the relationship between the Naples prognostic score (NS) and SYNTAX score (SS) in patients diagnosed with non-ST segment elevation myocardial infarction (NSTEMI), focusing on their implications for coronary artery disease (CAD) severity.
Material and Methods: Data were collected from 300 consecutive NSTEMI patients who underwent coronary angiography between January 2024 and May 2024. NS, calculated from serum albumin, total cholesterol, neutrophil/lymphocyte ratio (NLR), and lymphocyte/monocyte ratio (LMR), was assessed alongside SS, which quantifies CAD complexity based on angiographic findings.
Results: NS was significantly higher in patients with more extensive CAD, as indicated by higher SS (p < 0.05). This association underscores NS as a potential marker for predicting CAD severity in NSTEMI patients. Age was also noted to correlate significantly with higher NS, consistent with literature linking age to poorer nutritional status and cardiovascular outcomes.
Discussion: The findings of this study underscore the potential clinical relevance of the NS in patients with NSTEMI. NS, which integrates serum albumin levels, serum cholesterol levels, NLR, and LMR, emerged as significantly associated with the SS, a marker of CAD complexity. The study revealed that higher NS correlated with increased SS, suggesting that patients with poorer nutritional and inflammatory profiles may exhibit more extensive CAD. This association implies that NS could serve as a useful tool in risk stratification and management decisions for NSTEMI patients undergoing coronary angiography. Moreover, the study highlighted age and lipid profiles (triglycerides and LDL) as independent predictors of NS, further emphasizing the multifactorial nature of cardiovascular risk assessment in these patients.
Keywords: Naples Prognostic Score, Syntax Score, Coronary Artery Disease Severity
Introduction
Acute coronary syndrome (ACS) is a major cause of mortality and morbidity. The spectrum of ACS includes ST-segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina [1]. NSTEMI ACS, one of the types of ACS, is the result of partial occlusion of a coronary artery after rupture or erosion of a vulnerable atherosclerotic plaque [2].
The Naples prognostic score (NS) is a multidimensional, comprehensive prognostic assessment system based on serum albumin levels, serum cholesterol levels, neutrophil/lymphocyte ratio (NLR), and lymphocyte/monocyte ratio (LMR). This score can assess both the inflammatory and nutritional status of patients [3]. While neutrophils contribute significantly to atherosclerotic plaque destabilization, neutrophil count can be influenced by variables such as blood volume [4]. Lymphocytes and monocytes are key immune cells with important roles in the development of inflammation and atherosclerosis and influence prognosis in cases of myocardial infarction. Serum albumin is a negative acute phase reactant and its synthesis decreases and catabolism increases in response to inflammation [5, 6] .
The SYNTAX score (SS) is an angiographic scoring system that assesses the complexity of coronary artery disease (CAD) [7]. SS is recognized as a vital tool to guide decision-making between coronary artery bypass grafting (CABG) and PCI [8]. SS has been shown to aid revascularization decision-making and predict mortality and morbidity in patients with CAD [9].
In this study, we aimed to investigate the relationship between NS and SS in patients with NSTEMI in light of all these literature data.
Material and Methods
For this retrospective observational analysis, we collected data from 300 consecutive non-STEMI patients who underwent coronary angiography (CAG) between January 2024 and May 2024. Patients with active cancer, active autoimmune disease, active infections, and chronic kidney disease requiring hemodialysis and peritoneal dialysis were excluded.
ACS, unstable angina, NSTEMI and STEMI were defined as recommended in the latest universal myocardial infarction definition guideline [10]. Demographic and clinical parameters were recorded from the hospital database. Biochemical analyses including complete blood count, serum creatinine, serum albumin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and serum electrolyte levels were evaluated. Blood samples were collected at the time of admission to the emergency department.
Hypertension was defined as taking antihypertensive medication or having systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg. Diabetes mellitus (DM) was defined as fasting glucose level ≥126 mg/dl or receiving antidiabetic treatment.
Coronary angiography via femoral or radial access was performed for each patient. Two independent, experienced cardiologists individually evaluated the coronary angiographic images to calculate SS. Coronary arteries were assessed as 16 individual segments, and segments with 50% or greater luminal narrowing and ≥1.5 mm diameter were scored separately and combined to give a total score using the SS algorithm.
NS, serum albumin and serum TC levels were calculated using NLR and LMR ratios as described in Table 1.
Statistical Analysis
Statistical analysis was performed using the Statistical Package for Scientific and Social Sciences (IBM SPSS Statistics for Windows; IBM Corp., Armonk, New York, USA) software. Pearson chi-square test was used for categorical variables. The conformity of numerical variables to normal distribution was analyzed by statistical methods including the Kolmogorov-Smirnov test. Mann-Whitney U test was applied for non-normally distributed variables and Student’s t test was applied for normally distributed variables. Data are expressed as ‘mean ± standard deviation’ for normally distributed and ‘median (minimum and maximum)’ for non-normally distributed; categorical variables are expressed as ‘n (%)’. Univariate and multivariate logistic regression analyses were performed for independent predictors of Naples prognostic score. P < 0.05 was considered significant.
Ethical Approval
This study was approved by the Ethics Committee of Republic of Turkey Ministry of Health Bursa City Hospital (Date: 2024-05-29, No: 2024-9/7)
Results
The mean age of the 300 patients included in the study sample, of whom 31,3% were female, was 63 ± 10 years. 62.6% (n:188) of the patients had a Naples score of 0, 1, or 2 (group 1). The distribution of the demographic, clinical and angiographic characteristics of patients by groups is shown in Table 2.
In Group 2, compared to Group 1, age was significantly higher, while the smoking rate and EF were significantly lower (Table 1) (p <0.05). In patients with a high Naples score (Group 2), the SYNTAX score was significantly higher compared to Group 1 [9 (1.0-26.5)- 12 (2.0-37.0); p<0.001] (Table 2).
The distribution of the laboratory test results by the groups is shown in Table 2. In Group 2, the levels of neutrophils and NLR were significantly higher compared to Group 1, while the levels of, lymphocytes, LMR, triglycerides, total cholesterol, HDL, LDL, and albumin were significantly lower (p <0.05). There was no significant difference between the groups in other blood parameters (Table 2).
Univariable logistic regression analysis revealed that age, tobacco, EF, SYNTAX score, hemoglobin, triglyceride, HDL,LDL, BUN and creatinine were significantly associated with Naples score (Table 3). Further analysis of these variables with multivariable logistic regression analyses indicated that both age, SYNTAX score, triglycerides and LDL were independent predictors of Naples score (p < 0.05) (Table 3).
Discussion
This study revealed that NS was significantly higher in NSTEMI patients who underwent CAG and had more extensive coronary artery disease. NS was positively correlated with SS.
Being older age was also found to be significantly higher in group 2 patients. In the literature, age was found to be significantly associated with poor nutritional status, which is consistent with our study [11].
Hypoalbuminemia may be a risk factor for cardiovascular disease due to its detrimental pleiotropic effects on the cardiovascular system and the body [12]. Studies show that serum albumin levels are a reliable predictor of cardiovascular disease and are inversely associated with ischemic heart disease [13]. In another study, it was found that patients with low preoperative albumin levels had worse long-term survival after coronary artery bypass graft surgery compared to patients with normal albumin levels. The underlying cause may be related to the patient’s preoperative nutritional status, immune status or both [14].
Malnutrition has been investigated with increasing interest in recent years and is one of the hallmarks of frailty. Initially, malnutrition was thought to be predictive of poor clinical outcomes in cancer patients and various scores were developed to identify this condition, but in recent years, malnutrition has also been associated with mortality, morbidity and disease severity in cardiovascular diseases [15].
Previous studies have shown that NS can independently predict in-hospital mortality in STEMI [16]. Patients with high NS who underwent successful percutaneous intervention for NSTEMI had a higher composite major adverse cardiac event (MACE) of non-fatal recurrent myocardial infarction, cerebrovascular event and all-cause death at one-year follow-up, and high NS was found to be a predictor of MACE [17]. However, the association between NS and CAD severity in patients with NSTEMI has not been clearly established.
Naples prognostic score is calculated using serum albumin and serum TC levels, NLR and LMR ratios [18]. Neutrophils can secrete prooxidant and prothrombotic substances that can lead to endothelial damage and platelet aggregation leading to acute coronary syndromes. Low lymphocyte count has been associated with poor prognosis in patients with CAD and unstable angina [19]. NLR has been found to be used to differentiate patients at high risk of CVD events and more severe CAD [20]. Monocytes actively bind to platelets to form thrombotic monocyte-platelet aggregates, which are increased in STEMI [21]. Low lymphocyte count and high monocyte count have been associated with adverse cardiovascular endpoints in CAD patients [22]. Gong et al. found LMR to be an independent predictor of severe coronary atherosclerosis [23]. LMR has also been reported to be an effective predictor in patients with carotid artery stenosis and coronary atherosclerosis [24]. In another study, LMR was found to be an independent predictor of CAD severity in patients with stable CAD undergoing CAG [25]. Our findings reveal an association between NLR and LMR levels and severe CAD.
Conclusion
In conclusion, our study demonstrates a significant correlation between the NS and SS in patients with NSTEMI. The elevated NS in patients with more extensive coronary artery disease, as assessed by SS, highlights its potential as a valuable prognostic tool in NSTEMI management. Integrating NS alongside SS could enhance risk assessment and guide personalized treatment strategies for better patient outcomes. Further research is needed to validate these findings and explore the mechanistic links between NS and SS in cardiovascular 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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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Can Özkan, Yücel Kanal. Association of Naples Score with SYNTAX Score in Patients with Non-ST-Segment Elevation Myocardial Infarction. Ann Clin Anal Med 2024;15(11):789-793
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A single-center study of pertuzumab-trastuzumab chemotherapy versus trastuzumab-chemotherapy in neoadjuvant treatment of breast cancer
İlknur Deliktaş Onur 1, Hatice Gülgün Fırat 2, Elif Sertesen 1, Cengiz Karaçin 1, Öztürk Ateş 1
1 Department of Medical Oncology, 2 Department of Internal Medicine, Health Sciences University, Ankara Oncology Education and Research Hospital, Ankara, Turkiye
DOI: 10.4328/ACAM.22331 Received: 2024-07-18 Accepted: 2024-08-19 Published Online: 2024-09-17 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):794-798
Corresponding Author: İlknur Deliktaş Onur, Department of Medical Oncology, Health Sciences University, Ankara Oncology Education and Research Hospital, Ankara, Turkiye. E-mail: ilknurdeliktas382@gmail.com P: +90 531 458 14 40 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9884-5789
Other Authors ORCID ID: Hatice Gülgün Fırat, https://orcid.org/0000-0001-8230-3213 . Elif Sertesen Çamöz, https://orcid.org/0000-0002-1991-6620 . Cengiz Karaçin, https://orcid.org/0000-0002-7310-9328 . Öztürk Ateş, https://orcid.org/0000-0003-0182-3933
This study was approved by the Ethics Committee of Dr. Abdurrahman Yurtaslan Oncology Educatin and Research Hospital (Date: 26-07-2023, No: 2023-07/297)
Aim: In recent years, neoadjuvant chemotherapy constitutes the basic building blocks of thetreatment scheme in the treatment of breast cancer. Randomized controlled studies in recent years have shown that neoadjuvant chemotherapy and dual anti-Her2(human epidermal growth factor receptor 2) combinations increase the pathological complete response and contribute to overall survival in Her2 positive breast cancer. The aim of this study is to compare the pathological complete response rates of patients receiving neoadjuvant chemotherapy-trastuzumab (CT) and patients receiving neoadjuvant chemotherapy-trastuzumab-pertuzumab (CTP) and present real-life data.
Material and Methods: 79 patients who received neoadjuvant CT and 155 patients who received CTP were included in the study. Pathological complete response rates of two independent groups were compared. Variables that predicted pathological complete response in both groups were examined.
Results: In real life, we found that the pathological complete response rates in patients receiving neoadjuvant CTP were much higher than the rates in patients receiving neoadjuvant CT, even higher than the rates in randomized controlled studies that led to the introduction of dual blockade into the literature.
Discussion: We think that neoadjuvant chemotherapy and dual anti-Her2 therapy are the optimal treatment for Her2 positive breast cancer.
Keywords: Neoadjuvant Therapy, Breast Cancer, Pertuzumab, Dual Anti-Her2 Treatment, Pathological Complete Response
Introduction
In women, breast cancer is the most common type of cancer and the second leading cause of death from cancer [1]. Among breast cancers 20–25% of breast cancers overexpress HER2 (human epidermal growth factor receptor 2) and are associated with poor prognosis if untreated [2]. Signaling pathways that support cell proliferation, resistance to apoptotic signals, enhanced cell motility, and neoangiogenesis are constitutively activated as a result of HER2 gene amplification [3]. In comparison to chemotherapy alone, addition of trastuzumab, a HER2-directed humanized monoclonal antibody, dramatically increases response rate and overall survival in patients with metastatic HER2-positive breast cancer [4]. Trastuzumab inhibits ligand-independent signaling and prevents HER2 cleavage [5]. Specifically, between HER2 and HER3, ligand-dependent signaling is inhibited by pertuzumab, which is how it produces its effects. Trastuzumab and pertuzumab have complementary modes of action because they bind to separate locations [6].
In patients with localized or locally advanced Her2-positive breast cancer the pathological complete response rates (pCR) were increased by adding pertuzumab alongside trastuzumab as a neoadjuvant therapy [7]. In phase 2 neoSphere study, the pCR rate was increased by adding neoadjuvant docetaxel and trastuzumab alongside pertuzumab (29% vs. 46%). Another phase 2 trial, TRYPHANE, increased the effectiveness of trastuzumab-docetaxel by combining it with pertuzumab. In this study, the carboplatin arm’s pCR was 51%, compared to 45 and 50% in the anthracycline arms [8]. At the same time, studies have shown that pCR is associated with overall survival [9].
Our study aims to compare the pathological complete response rates of neoadjuvant pertuzumab-trastuzumab-chemotherapy and trastuzumab-chemotherapy. To evaluate the correlation of real-world data with the literature.
Material and Methods
The patients who received neoadjuvant chemotherapy and trastuzumab in 2014-2018, and patients who received neoadjuvant pertuzumab, trastuzumab and chemotherapy in 2018-2022 were evaluated in this retrospective study T1-T4 and N0-N3, Her2 positive breast cancer patients over 18 years of age, were included in the study. Patients, those had metastatic disease at the time of diagnosis, and patients who could not complete neoadjuvant four cycles of pertuzumab-trastuzumab therapy were excluded from the study. In the trastuzumab group, patients who could not complete the neoadjuvant 12-cycles trastuzumab were excluded from the study.
The pertuzumab was given at a dose of 840 mg (cycle 1), followed by 420 mg every 3 weeks. Trastuzumab was given every 3 weeks at 8 mg/ kg (cycle 1), followed by 6 mg/kg in the other cycles. In the group receiving only trastuzumab, trastuzumab was given as 4mg/kg in the first week and 2mg/kg in the following weeks. Docetaxel was given at 75-100 mg/m2 every 3 weeks. Paclitaxel was given at 80 mg/m2 on days 1, 8, and 15 or 175 mg/m2 every 3 weeks. Anthracycline protocol was administered to patients as Adriamycin cyclophosphamide (AC) or fluorouracil, epirubicin, and cyclophosphamide (FEC). The AC protocol contained 60 mg/m2 Adriamycin + 600 mg/m2 cyclophosphamide every 3 weeks. It contained fluorouracil at 600 mg/m2, epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 intravenously every 3 weeks in the FEC protocol. Patients received trastuzumab or trastuzumab emtansine (TDM-1) for 1 year after surgery.
Data of Her2 positive breast cancer patients receiving neoadjuvant chemotherapy were obtained from hospital records. The demographic characteristics of the patients, the treatment regimens they received in the neoadjuvant period, their surgical information, pathology reports, last examination dates, and if they died, date of death were recorded.
In this study, the primary endpoint was determined as pCR.The absence of invasive tumors in primary breast tissue and axilla was considered as a pathological complete response. The presence of only residual ductal carcinoma insutu(DCIS) was also evaluated as a pCR.
The patients were divided into two groups as those who received taxane pertuzumab trastuzumab and those who received taxane trastuzumab. Demographic features, clinicopathological features and pCR of these two groups were compared. Then, both groups were divided into two subgroups as those with and without pCR, and their clinicopathological features were compared.
Statistical Analysis
In the descriptive statistics of the study, continuous variables were used as mean (standard deviation), median (range); categorical variables were presented as frequency (percentage). Chi-square or Fisher’s Exact test was used to compare the categorical variables of two independent groups. Independent sample t-test for comparison of parametric data; The mann-whitney-u test was used to compare non-parametric data. A logistic regression model was created with variables with a p-value of <0.100, and independent factors predicting pathological complete response were identified.
Ethical Approval
This study was approved by the Ethics Committee of Dr. Abdurrahman Yurtaslan Oncology Educatin and Research Hospital (Date: 26-07-2023, No: 2023-07/297)
Results
A total of 79 patients in the trastuzumab group and 155 patients in the pertuzumab-trastuzumab group were included in the study. The median age was 49 years in both groups. While the T stage was distributed as T2-T4 in the group receiving trastuzumab, the T2 stage was predominant in the group receiving pertuzumab-trastuzumab (p<0.001, Table 1). While axilla positivity was observed in all patients receiving trastuzumab at the time of diagnosis, 11 (7.1%) of the patients receiving pertuzumab-trastuzumab were axilla negative at the time of diagnosis (p:0.015). Ki-67 median was 40 in both groups. Patients receiving neoadjuvant anthracyclines predominated in both groups, and a minority of patients in both groups received dose-dense AC. (Table-1)
The median age in the all-patient group was 49 years. When the factors predicting pathological complete response were evaluated in the all-patient group, the estrogen receptor status was observed to be significant (p:0.046), while the progesterone receptor status (p:0,107) and T-stage (0,087) were at the border. Estrogen receptor status was found to be significant when the logistic regression model was applied for all patients group.
The median age of patients with pCR and non-pCR was 53 vs 47 years in the trastuzumab group (p:0.022). In pertuzumab-trastuzumab group, premenopausal patients was found to be significantly higher in patients with pCR than in patients with non-pCR (53.7% vs. 36.4%, p:0.041). In the pertuzumab-trastuzumab group, progesterone receptor positivity was lower in patients with pCR than in patients with non-pCR (p:0.039). In pertuzumab-trastuzumab group estrogen receptor status, progesterone receptor status, and menopausal status were evaluated with a logistic regression model. Progesterone receptor (%95 CI 0,154-1,291 p:0.039) and menopause status (%95 CI 0,210-0,866 p:0.041) were the independent predictive factors for pCR. (Tabie-2)
When the pathological complete response rates of the patients receiving trastuzumab and the patients receiving pertuzumab-trastuzumab were compared, pathological complete response was observed in 95 (61.2%) patients in the pertuzumab-trastuzumab group, while it was observed in 33 (41.7%) patients in the trastuzumab group. This difference was statistically significant (p:0.002).
Discussion
In our study, pathological complete response rates were found to be significantly higher in the group receiving dual blockade than in the group receiving only trastuzumab. In the neoSphere study, the pCR was found to be 45% in the group receiving pertuzumab-trastuzumab-dosataxel, while in our study, the pCR was found to be 61% in this group. In our study, it was thought that the pCR rates were higher because the patients also received anthracycline and cyclophosphamide in the neoadjuvant period [10].
In our study, the difference between the pathological complete response rates of patients receiving trastuzumab and those receiving pertuzumab-trastuzumab was significant. Since the study was retrospective, the patients were not distributed at similar stages in both groups. The frequency of T4 and N3 disease was higher in the group receiving trastuzumab. This difference was not statistically significant, but it was thought that starting neoadjuvant therapy at a later stage might reduce the pathological complete response and make the difference between the two groups more significant. The fact that the patients were more advanced in the trastuzumab group reflects the shift in our treatment trend to neoadjuvant therapy after the dual blockade. Likewise, the tendency of surgeons in recent years is to refer patients to neoadjuvant treatment at an earlier stage.
In the pertuzumab group, 53(%55.7) of the patients with pathological complete response were progesterone receptor positive, while 42(%44.3) patients were negative. In the group non-pCR, 40 (72.7%) patients were progesterone receptor positive and 15 (27.3%) patients were progesterone receptor negative. Pathological complete response was found to be lower in progesterone receptor-positive patients, this result was consistent with the literature [11]. It is known that the frequency of residuals after neoadjuvant therapy in triple-positive breast cancer is higher than in the Her2 positive-hormone receptor negative group [12]. In a study published in 2016, pathological complete response rates were compared according to tumor subtypes. The rate of pCR in Her2 and ER and PR positive patients was found to be lower than in Her2 positive patients and ER and PR negative patients [11]. It is associated with a lower treatment response of the hormone receptor-positive component.In the all-patient group, pathological complete response was found to be statistically lower in estrogen receptor-positive patients. Pathological complete response was significantly higher in premenopausal patients in the pertuzumab group(p:0.039)In the study conducted by Silva et al., pCR was found to be high in premenopausal patients, as in our study [13]. In addition, there are also studies in the literature that support the opposite. In a study conducted in France in 2021, it was determined that the pathological complete response was seen at a lower rate in young and premeopausal Her2 positive patients, and this situation was associated with low DFS [14]. Similarly, in another study published in 2013, a lower rate of pathological complete response was found in premenopausal Her2 positive patients [15]. But it is also known that the tumor is more aggressive in young premenopausal patients [16]. The higher detection of pathological complete response in premenopausal patients in our study may be associated with a better response of aggressive tumors to neoadjuvant chemotherapy. This result suggested that aggressive tumors may benefit more from the neoadjuvant dual blockade.
Limitation
As for the limitations of our study; since it was retrospective, the clinicopathological features of the patients were not similarly distributed in the trastuzumab and pertuzumab-trastuzumab groups. Survival analyses could not be performed because the median follow-up time was short.
Conclusion
In conclusion, it is the standard combination of dual anti-Her2 and chemotherapy in neoadjuvant treatment in Her2 positive breast cancer. It has been shown in prospective studies and real-life data that it increases the pathological complete response
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
References
1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021 [published correction appears in CA Cancer J Clin. 2021;71(4):359.
2. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009;14(4):320-368.
3. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-172.
4. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-792.
5. Junttila TT, Akita RW, Parsons K, Fields C, Phillips GDL, Friedman LS, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2011;13;20(6):818]. Cancer Cell. 2009;15(5):429-440.
6. Nahta R, Hung MC, Esteva FJ. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res. 2004;64(7):2343-2346.
7. González-Santiago S, Saura C, Ciruelos E, Alonso JL, Morena PDL, Eslava MS, et al. Real-world effectiveness of dual HER2 blockade with pertuzumab and trastuzumab for neoadjuvant treatment of HER2-positive early breast cancer (The NEOPETRA Study). Breast Cancer Res Treat. 2020;184(2):469-479.
8. Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-2284.
9. Gianni L, Pienkowski T, Im YH, Tseng L-M, Liu M-C, Lluch A, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): A multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791-800.
10. Ates O, Oksuzoglu OB, Aktas BY, Karadag I, Esen S, Karakaya S, et al. Evaluation of factors predicting pathologic complete response in locally advanced HER2 positive breast cancer treated with neoadjuvant pertuzumab, trastuzumab and chemotherapy: Real life data. J BUON. 2021;26(4):1398-1404.
11. Niikura N, Tomotaki A, Miyata H, Iwamoto T, Kawai M, Anan K, et al. Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21,755 patients from the Japanese breast cancer registry. Ann Oncol. 2016;27(3):480-487.
12. Bhargava R, Dabbs DJ, Beriwal S, Yildiz IA, Badve P, Soran A, et al. Semiquantitative hormone receptor level influences response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer. Mod Pathol. 2011;24(3):367-374.
13. Silva LRD, Vargas RF, Shinzato JY, Derchain SFM, Ramalho S, Zeferino LC. Association of Menopausal Status, Expression of Progesterone Receptor and Ki67 to the Clinical Response to Neoadjuvant Chemotherapy in Luminal Breast Cancer. Associação de status menopausal, expressão de receptor de progesterona e de Ki67 à resposta clínica à quimioterapia neoadjuvante no câncer luminal de mama. Rev Bras Ginecol Obstet. 2019;41(12):710-717.
14. Laas E, Bresset A, Féron JG, Gal CL, Darrigues L, Coussy F, et al. Her2-positive breast cancer patients with pre-treatment axillary involvement or postmenopausal status benefit from neoadjuvant rather than adjuvant chemotherapy plus trastuzumab regimens. Cancers (Basel). 2021;13(3):370.
15. Kim MM, Allen P, Gonzalez-Angulo AM, Woodward W, Meric-Bernstam F, Buzdar AU, et al. Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer. Ann Oncol. 2013;24(8):1999-2004.
16. Anastasiadi Z, Lianos GD, Ignatiadou E, Harissis HV, Mitsis M. Breast cancer in young women: An overview. Updates Surg. 2017;69(3):313-317.
Download attachments: 10.4328.ACAM.22331.pdf
İlknur Deliktaş Onur, Hatice Gülgün Fırat, Elif Sertesen, Cengiz Karaçin, Öztürk Ateş. A single-center study of pertuzumab-trastuzumab chemotherapy versus trastuzumab-chemotherapy in neoadjuvant treatment of breast cancer. Ann Clin Anal Med 2024;15(11):794-798
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Relationship between ınflammatory parameters and total IgE values in patients diagnosed with asthma
Orhan Kayakıran, Suat Konuk, Emine Özsarı
Department of Pulmonology,Abant Izzet Baysal University Hospital, Bolu, Turkiye
DOI: 10.4328/ACAM.22345 Received: 2024-07-29 Accepted: 2024-09-02 Published Online: 2024-10-03 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):799-802
Corresponding Author: Orhan Kayakiran, Department of Pulmonology,Abant Izzet Baysal University Hospital, Bolu, Turkiye. E-mail: orhankayakiran.7@gmail.com P: +90 538 236 10 11 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8419-7039
Other Authors ORCID ID: Suat Konuk, https://orcid.org/0000-0002-8240-4775 . Emine Özsari, https://orcid.org/0000-0001-5842-7849
This study was approved by the Ethics Committee of Bolu Abant Izzet Baysal University (Date:2023-07-10, No: 2023/216)
Aim: In this study, we aimed to investigate the relationship between Total IgE levels obtained during follow-up of asthma patients receiving moderate to high dose inhaled corticosteroid therapy with a pre-diagnosis of lower respiratory tract infection, and post-treatment, with infective parameters, hospitalization, and frequency of attacks.
Material and Methods: Retrospective analysis was conducted on 132 patients diagnosed with asthma, despite the use of moderate to high dose inhaled steroids, based on their medical history, pulmonary function tests, and laboratory investigations.
Results: The frequency of Total IgE levels being 100 or higher in patients hospitalized in the last year and the frequency of decrease in Total IgE levels with a decrease in CRP levels were statistically significantly higher among the patients included in the study. In conclusion, the frequency of attacks and hospitalizations was statistically significant in patients with variable Total IgE levels.
Discussion: We observed statistically significant increase in Total IgE levels in patients followed with a preliminary diagnosis of lower respiratory tract infection. Additionally, a significant correlation was observed between elevated Total IgE levels and patients who experienced exacerbations within a year and those hospitalized due to asthma attacks. This suggests that Total IgE may be valuable both in predicting the severity of the disease and in assessing the risk of exacerbation within a year in asthma patients. Furthermore, the data in our study suggest that serum Total IgE levels may be valuable as a biomarker in patients with Asthma-COPD overlap.
Keywords: Asthma, Total Ige, Ashtma Attack
Introduction
Asthma is a heterogeneous disease characterized by chronic airway inflammation and variable airflow limitation. The clinical features, natural course, pathophysiological mechanisms, and treatment response of the disease vary among different asthma types. The best-known endotype of asthma is Type 2 asthma, characterized by the presence of Th2 cytokines accompanying airway and peripheral blood eosinophilia. IgE is a major immunoglobulin involved in allergic response and parasitic infections. Total and antigen-specific IgE measurements assist in the diagnosis of allergic diseases. Although IgE levels are not specific for the diagnosis of asthma, they are a critical factor in the development of bronchial hyperreactivity in asthmatics. In our study, we investigated the relationship between Total IgE and infectious parameters during follow-up of asthma patients receiving medium to high-dose ICS therapy with a pre-diagnosis of lower respiratory tract infection, as well as the relationship between Total IgE levels and asthma attacks and hospitalizations experienced in the last year. [1- 3 ]
Material and Methods
The inclusion criteria for the study were as follows: patients diagnosed with asthma who presented to the Chest Diseases Clinic of Bolu Abant Izzet Baysal University Training and Research Hospital, had symptoms despite using medium to high doses of inhaled steroids, had laboratory tests (complete blood count, CRP, Total IgE, control Total IgE) performed, and had chest X-rays requested at the time of evaluation. Exclusion criteria included those diagnosed with any rheumatological disease, those who received steroid treatment for any indication other than asthma, those diagnosed with any allergic disease other than asthma, those using anti-IgE therapy, and those diagnosed with immunodeficiency. This study is a retrospective cohort study. The study population consisted of patients who presented to the Chest Diseases Clinic of Bolu Abant Izzet Baysal University Training and Research Hospital between 01.01.2017 and 01.01.2021 and met the criteria.
Ethical Approval
This study was approved by the Ethics Committee of Bolu Abant Izzet Baysal University (Date: 2023-07-10, No: 2023/216)
Results
The mean age of the patients included in the study was determined to be 63.53±12.95 years. 62.12% of the participants (n=82) were male. It was observed that 51.52% of the patients (n=68) had a Total IgE value of 100 or higher, 75.76% (n=100) had a CRP value of 5 mg/dL or higher, and 12.12% (n=16) had an eosinophil count of 0.4 x 10^3/µL or higher. In the study, radiological findings were present in 61.07% of the patients (n=80) on Posterior-Anterior chest X-rays. 82.58% (n=109) had obstructive respiratory function tests, 10.61% (n=14) had normal results, and 4.55% (n=6) had a restrictive pattern. It was determined that 52.27% of the patients (n=68) were hospitalized, and 48.48% (n=64) had asthma attacks. In 30.30% of the patients (n=40), there was a decrease in Total IgE with a decrease in CRP levels. The percentage of patients evaluated as Asthma-COPD Overlap (ACO) was 11.36% (n=15).
In the study, the frequency of patients with Total IgE levels of 100 and above was statistically significantly higher among those with CRP levels of 5 mg/dL and above (p<0.01).
In the study, the frequency of patients hospitalized for asthma attacks during one year, with Total IgE levels of 100 and above, the frequency of asthma attacks, and the frequency of a decrease in Total IgE with a decrease in CRP levels were statistically significantly higher (p<0.01).
The frequency of patients hospitalized with obstructive spirometry findings was higher than those not hospitalized, while the frequency of having normal spirometry findings was lower. There was a statistically significant difference between the groups (p<0.01) (Table 1).
In the study, the frequency of patients experiencing attacks within the last year, with Total IgE levels of 100 and above, and the frequency of a decrease in Total IgE with a decrease in CRP levels were statistically significantly higher (p<0.01).
The frequency of patients experiencing attacks having an obstructive pattern in spirometry was higher than those without attacks, while the frequency of having a normal pattern was lower. There was a statistically significant difference between the groups (p<0.01) (Table 2).
In the study, the frequency of total IgE levels being 100 and above in patients evaluated as Asthma-COPD Overlap was statistically significantly higher than in patients not evaluated as Asthma-COPD Overlap.
The frequency of radiological findings in the Posterior-Anterior chest X-rays of patients with CRP levels of 5 mg/dL and above was statistically significantly higher compared to those with CRP levels below 5 mg/dL (p<0.01).
In the study, patients with a decrease in CRP accompanied by a decrease in total IgE were found to have a statistically significantly higher frequency of hospitalization and asthma attacks (p<0.01) (Table 3).
Discussion
In our study, the symptoms, physical examination findings, and radiological evaluations of patients diagnosed with asthma and receiving medium to high dose inhaled corticosteroid treatment were considered as a preliminary diagnosis of lower respiratory tract infection. According to the Turkish Thoracic Society Asthma guideline, asthma is reported to be more common in females compared to males in our country. [4] However, in our study, the proportion of male participants was higher than females (62% male participants). Additionally, the average age of asthma onset is reported to be 50 years, but the average age of our patients was 63. We believe that the distribution of gender and age in our study is related to our inclusion and exclusion criteria.
In our study, it was observed that some patients had elevated total IgE levels. In studies conducted in the literature, it is also reported that serum total IgE levels are elevated in adults with allergic asthma. [5] Furthermore, it has been stated that elevated Total IgE levels are associated with asthmatic patients. [6]
In spirometric evaluations of the patients, it was observed that most of them had an obstructive pattern. However, normal and restrictive patterns were also observed in some patients. This suggests that spirometry values in asthma patients can vary between obstructive and normal due to reversible airway obstruction observed in asthma. Additionally, restrictive spirometry findings may rarely be observed in advanced stages of the disease. A low FEV1 value under treatment (especially <60%) suggests that the patient is at risk for asthma attacks and persistent airflow limitation.
Among the infective parameters, it was observed that patients with CRP levels of 5 mg/dL and above had elevated total IgE levels. Additionally, it was observed that patients who had attacks had high total IgE levels and a decrease in total IgE with a decrease in CRP. These results indicate that total IgE levels may increase in relation to infections in asthma-diagnosed patients.
In a study, it has been stated that atypical bacterial pneumonia pathogens play an important role in the pathogenesis of asthma, and it has been concluded that C. pneumoniae infection can trigger IgE-specific responses in asthmatics. [7] In our study, we also observed a statistically significant elevation of Total IgE in patients followed up with a pre-diagnosis of lower respiratory tract infection. With this result, we conclude that lower respiratory tract infections may lead to Total IgE elevation in patients diagnosed with asthma. However, due to not including microbiological culture evaluation in our study, we cannot reach a conclusion associated with the pathogen.
Patients who experienced asthma attacks or were hospitalized in the last year, included in the study, showed a statistically significant frequency of Total IgE levels being 100 or higher, and a frequency of decrease in Total IgE levels with a decrease in CRP levels. Similar evaluations have been analyzed in previous studies, and similar results have been obtained with our study. In one study, increased total IgE levels were found to have a negative correlation with lung function in patients with a history of asthma. [8]Another study conducted in Spain reported that there was no significant relationship between disease severity or degree of airflow limitation, but a higher percentage of patients in the severe asthma subgroup had IgE levels >400 IU/mL. [5] In another study, the authors concluded that the asthma control test score was significantly lower in patients with IgE increase or decrease compared to patients with unchanged IgE levels. However, they found that these patients experienced more acute exacerbations within one year. [9] These results indicate that variable IgE levels over time are associated with poor asthma control. In our study, a significant correlation was observed between increased Total IgE levels and patients experiencing attacks within one year. This suggests that Total IgE may be valuable both in predicting disease severity and assessing the risk of asthma attacks within one year. A similar situation was observed for patients hospitalized in the last year, and variable Total IgE levels in controls may be valuable in predicting hospitalization within one year [10].
Limitations of the study include:
Inability to perform culture studies
Inability to perform procalcitonin studies
Low number of ACO patients
Conclusion
Despite these limitations, the results of our study indicate that total IgE levels may be an important biomarker in asthma patients and may vary in relation to infections.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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9. Tanaka A, Jinno M, Hirai K, Miyata Y, Mizuma H, Yamaguchi M, et al. Longitudinal increase in total IgE levels in patients with adult asthma: An association with poor asthma control. Respir Res. 2014;20;(1):144.
10. Peng J, Wang M, Wu Y, Shen Y, Chen L. Clinical ındicators for asthma-COPD overlap: A systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2022;12(17)2567-2575.
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Impact of subchorionic hematoma on maternal serum alpha-fetoprotein levels and second trimester screening outcomes in threatened abortion cases
Tugrul Basar 1, Abdurrahman Alp Tokalioglu 1, Rıza Dur 1, Tufan Arslanca 2, Metin Altay 1
1 Department of Obstetrics and Gynecology, Faculty of Medicine, University of Health Sciences, Etlik Zubeyde Hanim Women’s Health Training and Research Hospital, 2 Department of Obstetrics and Gynecology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.22347 Received: 2024-07-31 Accepted: 2024-09-02 Published Online: 2024-09-18 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):803-807
Corresponding Author: Abdurrahman Alp Tokalioglu, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Health Sciences, Etlik Zubeyde Hanim Women’s Health Training and Research Hospital, Ankara, Turkey. E-mail: alptokalioglu@gmail.com P: +90 532 789 70 96 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1776-2744
Other Authors ORCID ID: Tugrul Basar, https://orcid.org/0000-0003-2028-0647 . Rıza Dur, https://orcid.org/0000-0002-9225-9030 . Tufan Arslanca, https://orcid.org/0000-0001-9686-1603 . Mehmet Metin Altay, https://orcid.org/0000-0001-6772-858X
This study was approved by the Ethics Committee of Etlik Zubeyde Hanım Women’s Health Education and Research Hospital (Date: 2016-02-25, No: 205)
Aim: This study aims to examine the effects of subchorionic hematoma (SCH) on maternal serum alpha-fetoprotein (MSAFP) levels and the outcomes of second-trimester triple screening tests in patients who were diagnosed with threatened abortion during the first trimester.
Material and Methods: A retrospective study involved 922 patients who were diagnosed with threatened abortion between August 2013 and August 2015. After excluding cases of abortion, lack of follow-up, and those that did not meet inclusion criteria, 435 patients were included. Out of these, 102 had SCH (Group 1) while 248 did not (Group 2). Data collected comprised demographic characteristics, ultrasound findings, and triple screening test results. Statistical analyses included the use of student’s t-test, chi-square test, and correlation analysis. Additionally, ROC analysis was conducted to evaluate the diagnostic value of SCH as a predictor for elevated MSAFP levels.
Results: The patients had an average age of 27.5 ± 5.6 years, and the mean gestational age at the time of diagnosis was 10.8 ± 3.1 weeks. Patients with SCH showed significantly higher MSAFP levels compared to those without SCH (413 ± 178 ng/mL vs. 393 ± 255 ng/mL, p=0.036). However, no significant differences in MoM values or NTD risk were detected between the groups. Correlation analysis revealed a low yet significant correlation between AFP levels and hematoma size (r=0.231, p=0.020). ROC analysis revealed that while SCH is a significant factor for elevated MSAFP levels, it exhibits low sensitivity and specificity (AUC: 0.571, 95% CI: 0.507-0.636, p=0.033).
Discussion: SCH is linked to elevated MSAFP levels in patients experiencing threatened abortion in the first trimester. However, SCH does not have a significant impact on MoM values or NTD risk in second trimester screening tests. Clinicians should take SCH into account when interpreting elevated MSAFP levels and monitor patients with larger hematomas more closely. Further research is required to better understanding the clinical implications and improve the management of pregnancies complicated by SCH.
Keywords: Subchorionic Hematoma, Maternal Serum Alpha-Fetoprotein, Threatened Abortion, Second Trimester Screening, Neural Tube Defects
Introduction
Threatened abortion also known as imminent miscarriage, is characterized by vaginal bleeding and abdominal pain during the first trimester of pregnancy, with a closed cervix and the fetus still viable inside the uterus. It affects approximately 20-25% of all pregnancies. Approximately 20-25% of these patients are found to have a subchorionic hematoma (SCH) during ultrasonographic evaluation. SCH is believed to result from the partial detachment of the chorionic membranes from the uterine wall, leading to an accumulation of blood between the uterine wall and the chorion [1, 2].
The second-trimester screening test typically includes measurements of maternal serum human chorionic gonadotropin (MShCG), maternal serum alpha-fetoprotein (MSAFP), and maternal serum unconjugated estriol (MSuE3). Elevated MSAFP levels are a significant marker for neural tube defects (NTDs), which are severe congenital anomalies of the central nervous system [3]. In addition to NTDs, elevated MSAFP levels may also signal other conditions, such as fetal, placental, and maternal complications, including fetomaternal hemorrhage, which is the most common cause of elevated MSAFP levels aside from NTDs [4].
Alpha-fetoprotein (AFP) is the primary protein produced by the fetal liver and yolk sac and is present in the fetal circulation. It enters the maternal circulation via transplacental diffusion and the amniotic fluid. In non-pregnant women, serum AFP levels are around 1-2 ng/mL, however during pregnancy, MSAFP levels increase by approximately 15% per week from the 12th to the 32nd week, reaching about 500-550 ng/mL at 32 weeks, and then gradually decrease until term [4, 5].
Previous studies have demonstrated an association between subchorionic hematoma in cases of threatened abortion and increased MSAFP levels. Seppala and Ruoslahti reported that 83% of pregnancies with threatened abortion at 13 weeks had elevated MSAFP levels, attributing this increase to fetomaternal hemorrhage [5]. Similarly, elevated MSAFP levels have been observed following invasive procedures like chorionic villus sampling (CVS) and amniocentesis due to secondary fetomaternal hemorrhage [6-9].
Given the potential impact of SCH on MSAFP levels and the associated risks, it is essential to understand the implications for second-trimester screening tests. This study aims to investigate whether the presence of subchorionic hematoma in patients diagnosed with threatened abortion during the first trimester affects MSAFP levels and the outcomes of the second-trimester triple screening tests. The study specifically focuses on the risk assessment for NTDs.
Material and Methods
Study Design and Patient Selection
This retrospective study was conducted at the Early Pregnancy Clinic of Etlik Zubeyde Hanım Women’s Health Education and Research Hospital. The medical records of 922 patients who presented with vaginal bleeding and were diagnosed with threatened abortion between August 2013 and August 2015 were reviewed. Inclusion criteria for the study were patients with a single viable pregnancy between 6 and 18 weeks, with no known systemic diseases or bleeding disorders. A total of 487 patients were excluded: 80 experienced miscarriage, 315 did not return for follow-up, and 92 did not meet the inclusion criteria. Ultimately, 435 patients were eligible for the study, of 102 having subchorionic hematoma (Group 1) and 248 without(Group 2).
Data were collected on patient demographics, including age, body mass index (BMI), gestational age at diagnosis, gravidity, parity, and ultrasound findings. Ultrasonographic evaluations were conducted using a GE Logiq P5 ultrasound machine equipped with both transabdominal and transvaginal probes performed by two obstetricians. The size and location of subchorionic hematomas were recorded. The triple screening test results, including AFP levels, corrected MoM values, and NTD risk, were retrieved from the hospital’s information system.
Statistical Analysis
Data analysis was performed using SPSS for Windows version 11.5. Descriptive statistics were calculated for both demographic and clinical characteristics. The Student’s t-test was applied to compare normally distributed continuous variables between groups, while categorical variables were analyzed using chi-square test (Pearson, Yates correction, and Fisher’s exact test). Correlation analysis was conducted to assess relationships between continuous variables. A p-value <0.05 was considered statistically significant. ROC analysis was performed to determine cut-off values.
Ethics Approval
This study received approval from the Ethics Committee of Etlik Zubeyde Hanım Women’s Health Education and Research Hospital (Date: 2016-02-25, No: 205).
Results
Table 1 displays the demographic characteristics of the 350 patients included in the study. The average age of the patients was 27.5 ± 5.6 years, with a mean gestational age of was 10.8 ± 3.1 weeks at the time of diagnosis. Comparing the demographic characteristics between the SCH-positive and SCH-negative groups, the mean age was similar (27.5 ± 5.5 years vs. 27.5 ± 5.7 years, p=0.748). However, BMI was significantly higher in the SCH-negative group than in the SCH-positive group (25.4 ± 4.5 vs. 24.2 ± 3.9, p=0.011).
The average gravidity and parity were similar between the two groups (gravidity: 2.2 ± 1.2 vs. 2.3 ± 1.4, p=0.787; parity: 0.78 ± 0.86 vs. 0.76 ± 0.91, p=0.647). The mean gestational age at diagnosis did not differ significantly between the groups (10.7 ± 3.0 weeks vs. 10.8 ± 3.1 weeks, p=0.920) (Table 1). No significant differences were in age, gravidity, and parity between the groups.
Previous Pregnancy Outcomes and Smoking Status
Comparing previous pregnancy outcomes and smoking status no significant differences were observed between the groups in terms of abortion, ectopic pregnancy, voluntary curettage, or smoking habits.
Triple Screening Test Results
Table 2 presents the results of the triple screening tests. A significant difference in AFP levels was observed between the SCH-positive and SCH-negative groups (413 ± 178 ng/mL vs. 393 ± 255 ng/mL, p=0.036). The mean MoM values were comparable between the two groups (1.1 ± 0.4 vs. 1.0 ± 0.7, p=0.689). Similarly, the gestational age at the time of screening did not significantly differ between the groups (17.1 ± 0.7 weeks vs. 16.9 ± 0.8 weeks, p=0.071). The NTD risk was similarly comparable between the groups (3% vs. 4.4%, p=0.765).
Correlation analysis revealed a low yet significant correlation between AFP levels and hematoma size (r=0.231, p=0.020). No significant correlation was found between AFP levels and hematoma location (r=0.450, p=0.081). Additionally, no significant correlations were observed between AFP levels and maternal age, gravida, parity, or gestational age.
The comparison of NTD risk with MSAFP cut-off levels is summarized in Table 3. Among patients with MSAFP levels <2.0 MoM, 96.2% had a normal NTD risk, while 3.8% had an increased NTD risk. In contrast, among patients with MSAFP levels ≥2.0 MoM, 62.5% had a normal NTD risk, while 37.5% had an increased NTD risk. This difference was statistically significant (p<0.001).
ROC Curve Analysis
The ROC curve analysis was utilized to evaluate the diagnostic performance of subchorionic hematoma as a variable for elevated MSAFP levels. The area under the curve (AUC) was 0.571 (95% CI: 0.507-0.636, p=0.033), indicating that subchorionic hematoma is a significant predictor of elevated MSAFP levels. However, the variable demonstrates low diagnostic accuracy, with a sensitivity 62.7%, and specificity 51.4% ( (Figure 1).
Discussion
This study investigated the impact of subchorionic hematoma (SCH) on MSAFP levels and triple screening test outcomes in patients diagnosed with threatened abortion during the first trimester. Our findings indicate that the presence of SCH is associated with elevated MSAFP levels. However, there were no significant differences in MoM values or NTD risk between patients with and without SCH.
The observed rise in MSAFP levels in patients with SCH aligns with previous studies that have associated elevated MSAFP levels with fetomaternal hemorrhage [10, 11]. For instance, Seppala and Ruoslahti found elevated MSAFP levels in 83% of pregnancies with threatened abortion at 13 weeks, attributing this to fetomaternal hemorrhage [4]. Similarly, Christmas et al. examined the effect of fetomaternal hemorrhage on adverse pregnancy outcomes in patients with elevated second-trimester maternal serum AFP levels and found a significant correlation [11]. In this regard, Lachman et al. reported that the detection and measurement of fetomaternal hemorrhage using serum alpha-fetoprotein and the Kleihauer technique confirmed these observations [7].
Notwithstanding, elevated MSAFP levels have been observed following invasive procedures like chorionic villus sampling (CVS) and amniocentesis due to secondary fetomaternal hemorrhage. Katiyar and colleagues detected fetomaternal hemorrhage following CVS, which was associated with a rise in maternal serum alpha-fetoprotein levels [6]. Moreover, Fuhrmann et al. reported that maternal serum AFP levels increased following CVS due to fetomaternal hemorrhage [8]. Conversely, Makrydimas et al. investigated fetomaternal hemorrhage following coelocentesis and found no significant impact on AFP levels [13].
Despite the elevated MSAFP levels in patients with SCH, our study did not find significant differences in MoM values or NTD risk between the groups. This suggests that while SCH can elevate MSAFP levels, it may not substantially impact the accuracy of NTD risk assessment using triple screening tests. This finding is crucial for clinical practice as it indicates that SCH should be considered when interpreting elevated MSAFP levels, but it does not necessarily indicate a higher risk of NTDs. This aligns with the work of Maso et al., who observed that the presence of SCH did not significantly alter pregnancy outcomes [9].
The absence of a significant difference in MoM values and NTD risk between SCH-positive and SCH-negative groups could be attributed to several factors. First, the size of the hematoma may play a role. In our study, correlation analysis showed a low but significant correlation between AFP levels and hematoma size (r=0.231, p=0.020), indicating that larger hematomas are associated with higher AFP levels. However, the overall impact of hematoma size on MSAFP levels and subsequent NTD risk assessment may be limited. This finding is consistent with previous studies that have shown variable impacts of hematoma size on pregnancy outcomes. Similarly, Tuuli et al. conducted a meta-analysis and found that while SCH was associated with adverse pregnancy outcomes, the size of the hematoma was a critical factor in determining the level of risk [14].
Second, the timing of the hematoma’s formation and its resolution could influence MSAFP levels. Hematomas that resolve earlier in pregnancy may have less impact on second trimester screening results compared to those that persist. Regan et al. noted that the timing and resolution of hematomas significantly affected pregnancy outcomes, suggesting that early resolution might mitigate some risks [15]. Early resolution of SCH can lead to normalization of MSAFP levels, thereby reducing the potential for false-positive NTD screening results.
Another important consideration is the clinical management of patients with SCH. In our study, the lack of significant differences in adverse pregnancy outcomes such as abortion history, ectopic pregnancy, voluntary curettage, and smoking status between SCH-positive and SCH-negative groups suggests that the presence of SCH alone may not be a decisive factor in determining pregnancy outcomes. This aligns with previous studies that have shown variable impacts of SCH on pregnancy outcomes, with some studies reporting increased risks of adverse outcomes and others finding no significant associations. Stephenson et al., reported similar findings in a study involving 197 couples, where the presence of SCH did not consistently predict adverse outcomes [16].
Additionally, SCH may have a transient effect on MSAFP levels. Wilcox et al. demonstrated that early pregnancy losses are common and often associated with transient elevations in serum markers, including MSAFP [17]. This transient nature might explain why some studies, including ours, do not find long-term impacts of SCH on pregnancy outcomes despite initial elevations in MSAFP levels.
The findings of this study carry several clinical implications. First, the presence of SCH should be taken into account when evaluating elevated MSAFP levels during the second trimester. While elevated MSAFP levels may indicate an increased risk of NTDs, SCH can also contribute to these elevated levels. Therefore, clinicians should take into account the presence of SCH and potentially use additional diagnostic tools such as detailed ultrasound evaluations to accurately assess NTD risk. Alberman emphasized the importance of considering other diagnostic tools in conjunction with MSAFP levels to provide a comprehensive assessment [18]. Second, the correlation between hematoma size and AFP levels suggests that patients with larger SCH should be monitored more closely. These patients may require more frequent follow-up visits and additional diagnostic tests to ensure the well-being of the fetus and to manage any potential complications. Kurki and Ylikorkala suggested that close monitoring and follow-up are crucial in managing pregnancies complicated by SCH [19].
Furthermore, the results of this study underscore the importance of considering other potential factors that could influence MSAFP levels. For example, maternal weight, diabetes, and smoking status are known to affect MSAFP levels and should be taken into account when interpreting screening results. Blumenfeld and Brenner noted that various maternal factors, including thrombophilia and lifestyle choices, significantly influence MSAFP levels [20]. Additional research is necessary to investigate the influence of these factors on MSAFP levels in patients with SCH and to create more comprehensive risk assessment models that include these variables.
This study has several limitations. The retrospective design may introduce selection bias, and the sample size, particularly for patients with SCH, was relatively small. Additionally, the study did not consider other potential factors that might affect MSAFP levels, such as maternal weight, diabetes, and smoking status. Future research should focus on addressing these limitations by conducting larger prospective studies that account for these confounding factors. Additionally, investigating the longitudinal effects of SCH on pregnancy outcomes and MSAFP levels throughout pregnancy could provide valuable insights into the temporal dynamics of these associations. Harlap and Shiono emphasized the importance of prospective studies to gain a deeper understanding of long-term impacts of SCH on pregnancy outcomes [21]. Furthermore, the clinical significance of the low correlation between AFP levels and hematoma size warrants further investigation. Understanding the mechanisms underlying this correlation could provide valuable insights into the pathophysiology of SCH and its impact on pregnancy outcomes. For instance, examining the role of placental vascularization and the degree of fetomaternal hemorrhage in relation to hematoma size could help elucidate the biological processes driving the observed associations. Blumenfeld and Brenner noted the importance of understanding the pathophysiological mechanisms to improve clinical management and outcomes [20].
Conclusion
In conclusion, this study demonstrates that subchorionic hematoma is associated with elevated MSAFP levels in patients with threatened abortion during the first trimester. However, the presence of SCH does not significantly impact MoM values or NTD risk in second trimester screening tests. Clinicians should consider SCH when interpreting elevated MSAFP levels and monitor patients with larger hematomas more closely. Further research is needed to explore the clinical implications of these findings and to improve the management of pregnancies complicated by SCH.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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5. Seppälä M, Ruoslahti E. Alpha-fetoprotein in abortion. Br Med J. 1972;4(5843):769-71.
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7. Lachman E, Hingley SM, Bates G, Ward AM, Stewart C, Duncan S. Detection and measurement of fetomaternal haemorrhage: serum alpha-fetoprotein and the Kleihauer technique. Br Med J. 1977;1(6073):1377-9.
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13. Makrydimas G, Lolis D, Georgiou I, Navrozoglou I, Nicolaides KH. Feto-maternal bleeding following coelocentesis. Hum Reprod. 1997;12(4):845-6.
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Tugrul Basar, Abdurrahman Alp Tokalioglu, Rıza Dur, Tufan Arslanca, Metin Altay. Impact of subchorionic hematoma on maternal serum alpha-fetoprotein levels and second trimester screening outcomes in threatened abortion cases. Ann Clin Anal Med 2024;15(11):803-807
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Our experience in managing pregnancies during the Great Hatay Earthquake
Atilla Karateke, Raziye Keskin
Department of Gynecology and Obstetrics, Private Reyhanlı MMT American Hospital, Hatay, Turkey
DOI: 10.4328/ACAM.22352 Received: 2024-08-01 Accepted: 2024-09-09 Published Online: 2024-09-24 Printed: 2024-11-01 Ann Clin Anal Med 2024;15(11):808-811
Corresponding Author: Atilla Karateke, Department of Gynecology and Obstetrics, Private Reyhanlı MMT American Hospital, Hatay, Turkey. E-mail: drkarateke@gmail.com P: +90 534 741 26 98 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2539-8476
Other Authors ORCID ID: Raziye Keskin, https://orcid.org/0000-0003-2442-5786
This study was approved by the Ethics Committee of Adana City Education and Research Hospital (Date: 2024-05-30, No: 4)
Aim: This study aims to present information on the management and clinical outcomes of pregnant women following the major earthquake in Hatay.
Material and Methods: Data from 920 pregnant women who visited the obstetrics and gynecology clinic of the private Reyhanlı MMT American Hospital after the earthquake were retrospectively obtained from the electronic system. International diagnosis codes (ICD) X34 and Z-33 were used. SPSS was utilized to perform the data analysis.
Results: The average blood pressure of the pregnant women was 110/80 mmHg, with approximately 20 women (2.1%) having >140/90 mmHg. A total of 740 births (80.4%) were recorded. Of these births, 120 were normal vaginal deliveries and 620 were cesarean sections. Eighteen women (1.9%) underwent orthopedic, neurosurgical, and general surgical interventions. Five women experienced preterm births following these interventions. Seven women (0.94%) were diagnosed with and treated for post-traumatic stress disorder.
Discussion: Health institutions in Hatay, located in the earthquake fault zone, should develop strategies and programs to be prepared for earthquakes. These should be updated annually, and healthcare workers should be trained accordingly.
Keywords: Earthquake, Pregnancy, Cesarean
Introduction
On February 6, 2023, a highly severe earthquake centered in Kahramanmaraş affected 11 provinces. With a magnitude of 7.7, this natural disaster is one of the most devastating earthquakes in Turkish history. The earthquake resulted in over 50,000 deaths and more than 100,000 injuries. Many public and private hospitals either collapsed or became non-operational in terms of healthcare services [1].
As we know, our country is situated on active earthquake fault lines. In this geography, severe earthquakes occur in various regions every 10-15 years, leading to loss of life and injuries. Following these earthquakes, children and women are the most affected groups, with pregnant women being the most vulnerable among them [2].
Pregnancy is a distinctive period with its unique physiology and psychology. The changes brought about by pregnancy can lead to unpredictable situations during natural disasters like earthquakes. We face severe clinical conditions in pregnant women due to both the earthquake itself and the stress it induces. The most significant of these include spontaneous abortion, preterm birth with associated low birth weight infants, antenatal and postnatal infections, and postpartum post-traumatic stress disorder [3-5]. Managing these clinical conditions in earthquake-stricken areas with already compromised healthcare infrastructure is very challenging. A study indicated that the difficulty in managing the clinical conditions of earthquake victims is due to the failure to implement pre-established measures and deficiencies in early intervention rather than the severity of the earthquake itself.
The research seeks to analyze the management and clinical outcomes of pregnant women who presented to our clinic after the earthquake and provide information on the measures that can be taken and the strategies that need to be implemented in future natural disasters.
Material and Methods
The study took place in the obstetrics and gynecology clinic of the private Reyhanlı MMT American Hospital, and the data of pregnant women who presented to this clinic were obtained through a retrospective archive search. Pregnant women who presented between February 6, 2023, and June 6, 2023, and were diagnosed with ‘X34 – Earthquake victim’ and ‘Z33’ according to the International Classification of Diseases-10 (ICD-10) were included in the study. The data form created included demographic characteristics of the pregnant women, delivery types, antenatal and postnatal obstetric complications, presence of trauma-related injuries, and types of surgeries performed.
Using SPSS 21 software, the data were analyzed and reported as frequency (n) and percentage (%). A significant threshold p-value of <0.05 was considered.
Ethical Approval
This study was approved by the Ethics Committee of Adana City Education and Research Hospital (Date: 2024-05-30, No: 4).
Results
A total of 920 pregnant women who presented to our clinic in the four months following the earthquake were included in the study. The average age of the pregnant women was 29.7 ± 5.3 years.
The average blood pressure of the pregnant women was 110/80 mmHg, with approximately 20 women (n=20, 2.1%) having >140/90 mmHg. A total of 740 births (n=740, 80.4%) were recorded. Of these births, 120 (16.2%) were normal vaginal deliveries, and 620 (83.8%) were cesarean sections. The number of twin births was observed to be 3 (n=3, 0.4%).
Among those who delivered by cesarean section, 5 cases experienced uterine atony, and 3 (0.4%) underwent hysterectomy. All 5 patients received erythrocyte transfusions. (Table-1)
Postpartum infections were observed in 7 patients (n=7, 0.94%).
During the first 10 days, patients stayed in the hospital for an average of 12 hours, with 1 day being the subsequent days.
The number of pregnant women who experienced preterm labor was 18 (n=18, 2.4%). Every baby was taken to the neonatal intensive care unit.
The number of pregnancies that resulted in spontaneous abortion was 11 (n=11, 1.4%).
Eighteen pregnant women underwent orthopedic, neurosurgical, and general surgical interventions. Five of these women experienced preterm labor after these interventions.
Twelve pregnant women who underwent trauma surgery received physical therapy and rehabilitation in the later period.
The number of pregnant women diagnosed with and treated for post-traumatic stress disorder was 7 (n=7, 0.94%).
Discussion
This study is designed to evaluate the impact of the earthquake on pregnant women in the context of existing literature. Our hospital was almost the only fully operational institution remaining in the Amik Plain immediately after the earthquake. From the initial hours of the disaster, all affected individuals, either by their own means or through emergency services (112), were brought to our hospital. A large number of patients received their initial medical care. Trauma surgeries were performed, with some patients treated in our hospital and others referred to different provinces.
Earthquakes, as natural disasters, affect everyone. Nevertheless, the younger population, the elderly, and women are more significantly impacted [6]. Among women, pregnant women are the most affected due to physiological changes. Many studies published following earthquakes from various parts of the world report that pregnant women and children are the most affected groups. Similar to children, pregnant women are in this high-risk group due to their different physiology and the incomplete development of their immune systems [7].
The United Nations Fund reported that there were approximately 250,000 pregnant women in the earthquake zone, with 25,000 to 30,000 expected to deliver in the initial month after the earthquake [1].
A significant group of patients presenting to emergency services after the earthquake consisted of pregnant women. In the first 10 days, approximately 250 pregnant women sought medical help, either as walk-ins or through emergency services.
Of these pregnant women, 18 underwent non-obstetric surgical interventions. Despite effective medical treatment, preterm births occurred in about five of these cases. All of these newborns required neonatal intensive care, with some being treated in our unit and others transferred to different facilities. The number of births within the first 10 days was 25, with 22 of these being cesarean sections. Additionally, 12 pregnant women who underwent non-obstetric surgeries received long-term physical therapy rehabilitation programs.
The most significant clinical problem in crush syndrome, which emerges from the earthquake, is acute kidney failure. The primary treatment method for kidney failure due to muscle breakdown is dialysis. The presence of necessary equipment and adequate personnel to perform dialysis saved many lives. Observations post-earthquake revealed a significant lack of dialysis machines and essential equipment. Our hospital provided dialysis to many patients, including three pregnant women, all of whom survived the procedure.
The mandatory and non-deferrable follow-up of pregnancies under normal conditions was severely disrupted in our region due to the earthquake. One contributing factor was the limited availability of operational healthcare facilities, and another was the reluctance of pregnant women to visit health centers due to ongoing aftershocks.
In our clinic, approximately 920 pregnant women were followed up in the first four months after the earthquake. Routine blood pressure measurements during pregnancy follow-ups showed that the average blood pressure was higher compared to pre-earthquake levels. A significant increase in the number of pre-eclampsia cases was observed compared to before the earthquake. This was likely due to the intense anxiety caused by the earthquake. All patients diagnosed with pre-eclampsia received antihypertensive medical treatment. However, in five cases, severe pre-eclampsia led to the necessity of delivery. None of the postpartum patients experienced pre-eclamptic complications. All mothers were referred to the cardiology clinic for follow-up after discharge. Analysis of cardiology follow-ups indicated that as anxiety decreased over time, blood pressure levels returned to normal.
Deteriorating socioeconomic conditions, problems with food and shelter, and increased anxiety from frequent aftershocks led to a rise in the number of abortions, preterm births, and low birth weight infants among some of the pregnant women under follow-up [8-10]. The most significant reason for this was the widespread anxiety brought on by the frequent aftershocks [11-13].
Many previous studies have reported that earthquakes clearly cause preterm births and an increase in the number of low-birth-weight infants. For instance, a study by Tan et al. after an earthquake in China showed a significant increase in preterm births and low birth weight infants. Similarly, Kyozuka et al. found a significant increase in preterm births and low birth weight infants following the 2011 Great East Japan Earthquake, attributing this to problems with food, shelter, and intense anxiety [8].
In our clinic, a significant increase was observed in the number of spontaneous abortions, preterm births, and low-birth-weight infants. Eleven pregnant women experienced spontaneous abortions, with five undergoing revision curettage. Despite medical treatment, 18 pregnant women experienced preterm labor. All babies were admitted to the neonatal intensive care unit due to low birth weight and insufficient lung development.
The rate of cesarean sections significantly increased compared to pre-earthquake levels, while the length of hospital stay post-delivery, especially in the first 10 days after the earthquake, was less than 24 hours. The primary reason for this was the pregnant women’s desire to minimize their hospital stay due to aftershocks and their request for quick discharge once postoperative mobilization was achieved. The cesarean section rate was recorded at 83.8%, with the normal delivery rate at 16.2%. In the first 10 days, the postoperative stay was 12 hours on average, dropping to as low as 8 hours for some patients.
There was no significant increase in the rates of uterine atony compared to pre-earthquake levels. Despite the short postoperative hospital stay, the lack of increase in uterine atony rates was attributed to the effective and strong uterotonic medical treatment applied in the first six hours. Uterine atony occurred in five patients. Two benefited from medical and balloon treatment, while three underwent hysterectomy despite effective treatment. No perioperative complications occurred. All patients with uterine atony received erythrocyte transfusions, with no transfusion-related complications.
Postpartum infections increased as expected due to shelter problems brought on by the earthquake. Patients could not stay in hygienic environments and faced issues with food and shelter due to staying in tents or containers during the postpartum period [14]. This led to an expected increase in infections, but quick and effective intervention yielded successful results. All seven patients who developed postpartum infections received appropriate antibiotic therapy and wound care, and all were discharged in good health.
Stress from psychological changes during a normal pregnancy cycle was exacerbated by intense fear, and food and shelter problems post-earthquake [15-17]. To manage increased stress, both public and many private organizations provided significant psychosocial support after the earthquake. However, the difficulty in delivering this support promptly and the increased predisposition to depression before the earthquake led to post-traumatic stress disorder (PTSD) in many pregnant women.
Many studies have found that a significant number of pregnant women experienced antenatal and postnatal PTSD after earthquakes. Watanabe et al. reported that pregnant women experienced intense PTSD during the postpartum period after the Great East Japan Earthquake, with effects lasting for years [18]. Similarly, a study by Qu et al. following a major destructive earthquake in China found that PTSD lasted for 1-2 years in pregnant women [19]. Seven pregnant women who presented to our clinic were diagnosed with PTSD and followed up with appropriate treatments by the psychiatry clinic.
Limitations of study
The most important limitation of this article is its retrospective nature. Additionally, the small number of GDM patients and the single-center study are significant limitations.
Conclusion
Our country is situated on active fault lines and faces devastating earthquakes every 10-15 years. To minimize the negative impacts of earthquakes, healthcare institutions should prepare strategies and programs specifically for earthquake response. These programs should be routinely updated. Special teams from various regions of the country should be established and kept ready to reach the affected area immediately after an earthquake. One of our primary goals should be to minimize and manage obstetric and non-obstetric complications in pregnant women through pre-prepared programs.
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 compareable ethical standards.
Funding: None
Conflict of Interest
The authors declare that there is no conflict of interest.
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