Acute pancreatitis is the reversible paranchymal injury related to the pancreatic inflammation, which can be observed in local and distant extrapancreatic tissues.Gallstones are among the major causes.Small gallstones and sludge are the most frequent acute pancreatitis causes in the Western world[2,3]. If any etiological factor cannot be detected, the disease is referred to as idiopathic acute pancreatitis. However, some of these cases can be related to microlithiasis.
Acute pancreatitis caused by gallstones was defined in 1901 by Eugene Opie with the common canal theory.Gallstones fall to the duodenum in 70% of the cases[5,6].However, this situation may differ with the severity of acute pancreatitis, duration of the temporary obstruction in the middle canal or its persistance.
In this review, diagnosis, prediction criteria for pancreatitis severity, scoring systems and treatment approaches for acute biliary pancreatitis(ABP), which is among the most frequently observed acute pancreatitis.
The diagnosis of acute pancreatitis is made if at least two of the following three criteria are met: 1-Acute abdominal pain 2- Elevated pancreatic enzyme levels in blood, urine or acidic liquid 3- Abnormal imaging findings in pancreas that are related with acute pancreatitis.If the diagnosis is made on this basis, other pancreatic diseases and acute abdomen reasons can be ruled out.Distinguishing between acut biliary pancreatitis and other causes of acute pancreatitis is important for disease management and prognosis.
Symptoms and signs
Various clinical symptoms and signs, including abdominal pain, nausea, vomiting, ileus, subileus, reduced bowel sound, fever, jaundice, pain extending to the dorsum, shock, anorexia, abdominal muscular rigidity and neurological symptoms can be observed in acute pancreatitis.
Acute pancreatitis sometimes cause color change in the skin in side abdominal wall(Grey Turner’s sign), around the belly(Cullen’s sign), or on the lower part of inguinal ligament(Fox’s sign).
Abdominal pain is observed in approximately 95% of the cases.In patients with biliary pancreatitis, pain is localized more on the right upper quadrant[8,9].The presence of gallstones in patient history helps to consider ABP in the diagnosis. Vomiting is associated with peripancreatic inflammation extending to the posterior gastric wall and local/generalized ileus.
Other frequent symptoms and signs in patients with acute pancreatitis includepain extending to the dorsum, loss of appetite, jaundice, muscular defence, meteroism and hematemesis.
Current diagnostic biomarkers
Serum amilase and lipase levels are standard blood tests. Serum amilase levels increase rapidly in the onset ofacute pancreatitis (3-6 hours), persist for 3-5 days.Moreover, amilase levels may increase due to other reasons except acute pancreatitis, such as perforated peptic ulcer, perforated/obstructed bowel, mesenteric infarction, trauma, salivary diseases, cholecystitis andperitonitis. Lipase values are more sensitive compared to amilase. In addition to these, hyperglysemia, hypocalcemia, leukocytosis, anemia, moderate hyperbilirubinemia and an increase in liver enzyme levels can be observed.
In 2007, American Academy of Family Physicians emphasized to use amilsae and lipase values, whole blood count, blood urea, creatinine, glucose, calcium, triglyceride, urine examination and arterial blood gas in the diagnosis and treatment of acute pancreatitis. Additional research biomarkers may include trypsinogen activation peptide(TAP), CRP, procalcitonin, phospholipase A2 and the cytokines interleukin-6 and interleukin-8.
While several prognostic biomarkers, including procalcitonin, serum interleukin-6, interleukin-8, polymorphonuclear elastase and serum CRP, have been investigated, the research on diagnostic test had less efficiency[14,15].Certain interesting biomarkers have been defined; yet, when compared with lipase, their lower accuracy and requirement for slow techniques which are not suitable for clinical laboratories and fastdiagnosis prevented their widespread use.PhospholipaseA2, pancreatic elastase, urinetrypsinogen activated protein(TAP), carboxypeptidaseB(CAPB), activation peptide of carboxypeptidase B(CAPAP), trypsin-2-alpha1 antitrypsin complex(trypsin-2-AAT) and circulating(cell-free) DNA are examples for such laboratory biomarkers which did not find widespread use.
As a novel approach, “proteomics” studies have increasing importance and these studies accelarated following the completion of the human genome project, and found a widespread area of application. Despite the fact that genomics has been the dominant research area in biomedical studies in recent years, research on proteomics is rapidly spreading among scientific research groups and clinical research laboratories.Currently, there are ongoing proteomic studies on acute pancreatitis, and they are expected to have key positions to determine both diagnosis and prognosis. There are ongoing proteomics studies on novel potential biomarkers, including protein disulfide isomerase related protein, dnaK-type molecular chaperone hsp72-ps1, mitochondrial glutamate dehydrogenase, similar to chaperonin containing TCP-1β subunit, RuvB-like protein1, heterogeneous nuclear ribonucleoprotein H1, aldehyde reductase1, triosephosphate isomerase1, peroxiredoxin2, heat shock protein90, mitochondrial ATP synthaseβ chain precursor, tubulinβ chain, 3-mercaptopyruvate sulfurtransferase and mitochondrial ATP synthase subunit D.
Imaging finding of ABP
CT is the major imaging method to evaluate acute pancreatitis. It is important to detect the disease and to evaluate its severity.What is more important, probably, is that CT is considerably useful to evaluate situations presented with clinical symptoms similar to acute pancreatitis, such as duodenal ulcer perforation, ruptured aortic aneurism and mesenteric ischemia[17,18].
Ultrasonography(US)is a relatively sensitive method to evaluate gallbladder and biliary tracts, and its feasibility and mobility ensures point-of-care evaluation. However, the fact that the distal parts of the coledoc cannot be evaluated due to bowel gas superposition constitutes a disadvantage of this method. Stones causing acute pancreatitis are generally smaller than 5mm.
Magnetic resonance imaging(MRI) is considerably successful to show biliary tracts and pancreatic ducts that contain stable fluid. These sequences can be used to perform magnetic resonance cholangiopancreatography(MRCP), and it is the non-invasive alternative to endoscopic retrograde cholangiopancreatography(ERCP). For common bile duct stones, MRCP’s sensitivity and specificity is above 90%.
Identification of acute biliary pancreatitis
The first recommendation in ABP definition is to inspect the presence of stones in the gallbladder and/or coledoc usingUS. The sensitivity of US to detect gallstones exceeds 95% in uncomplicated cases. However, in cases of acute pancreatitis, the sensitivity is only 67-78% due to ileus and bowel distention. Furthermore, the sensitivity ranges between 25-90% for detecting common bile duct stones.Detecting especially small stones that cause pancreatitis, even the probability of these stones passing to the intestine makes the detection of common bile duct stones using US complicated.
Alanine aminotransferase (ALT), elevated γ-glutamyltransferase
(GGT) and bilirubin also leads to a suspection of ABP, but it should be noted that ABP may be present although these parameters have normal levels. If gallstones are not detected by US, and presence of jaundice and elevated biochemical parameters indicate ABP. MRCP and endoluminal US(EUS), which have higher sensitivity and specificity, should be performed. MRCP has high sensitivity(84-95%) and specificity (96-100%) to detect common bile duct stones. EUS, similar to MRCP, has high degree to detect stones in the main biliary tracts[21,22].
While only 3-7% of the patients who have gallstone in the gallbladder are known to develop pancreatitis, clearing residual gallstones by cholecystectomy or ERCP after pancreatitis prevents recurrent pancreatitis attacks. When left untreated, the recurrence rate of gallstone pancreatitis ranges between 32-61%.Sludge that causes stasis in biliary flow is among the causes of acute pancreatitis. Sludge consisting of cholesterol crystals and calcium granules may include stones smaller than 5mm. It forms a dense layer in the gallbladder. Behaving similarly to gallstones, it may cause acute pancreatitis and similarly, cleaning coledoc using cholecystectomy and ERCP may prevent recurrent pancreatitis attacks[24,25].
Experimental studies have demonstrated that biliary reflux was not a necessity for acute pancreatitis development, and pancreatitis may develop as a result of pancreatic duct obstruction.According to another theory, insufficient inhibition of intracellular trypsinogen activation leads to an increase in pressure in the pancreatic duct when exocrine pancreas is hyperstimulated, active trypsin reflux is elevated and thereby, pancreatic injury develops.
Biliary tract stones that cause pancreatitis may not be presented radiologically in all cases. The stone might have passed the Oddi sphincter or it could be really small, referred to as microlithiasis, which cannot be presented with conventional abdominal US.Microlithiasis condition may cause recurrent pancreatitis as the migration of the stones is easy. Moreover, hepatic transaminase levels are also normal in 15-20% of these cases.
In 1901, Eugene Opie proposed the “common channel theory”. Main biliary tract and pancreatic duct open to the duodenum with a common canal, and a gallstone localized to ampulla Vater causes an obstruction at this location, leading to gallbladder reflux and pancreatitis. Acosta andLedesma suggested that biliary reflux associated with the temporary obstruction in papilla, which is caused by the migration of gallstones to the duodenum, might cause pancreatitis.In the end, biliary reflux due to obstruction or gallbladder itself can damage the protective barrier in the pancreatic cells, or activate pancreatic enzymes via indirect mechanisms to cause pancreatitis.
Duodenal reflux theory is defined as the damage exerted by gallstones on the muscular layer of oddi sphincter during their migration to the duodenum, and subsequent retrograde flow of the duodenal content into the pancreatic duct.According to another theory, the increase in pancreatic permeability in the pancreatic duct due to the obstruction that is caused by the stones, can lead to pancreatic enzymes to overcome the protective barrier to cause pancreatitis.
Inflammation is generally limited to a localized zone of injury.However, in certain cases, the severity of inflammation turns into systemic inflammatory response syndrome(SIRS) due the overactivation of the inflammatory cascade which is regulated by cytokines, immunocytes and the complement system. Inflammatory cytokines cause macrophages to migrate to distant organs, such as lungs or liver. Immunocytes stimulated by the cytokines released from macrophages secrete more cytokines, free radical and nitric oxide. Certain cytokines and proteins that play roles in disease progression, including IL-1, IL-6, IL-8, IL-10, TNF- α, monocyt chemoattractant protein, macrophage inhibitor factor, C-reactive protein and serum amyloid A, are important for monitoring the disease.
Prediction of Disease Severity
The severity of the disease is evaluated by combining clinical and laboratory findings, and using Atlanta criteria, Ranson criteria and acute physiology and chronic health evaluation II(APACHE II)scoring system. CT severity index developed by Balthazar et al. is used to evaluate the disease severity.In this index, necrosis and presence, amount and extension of fluid collections are evaluated and a patient is given a score.
Serum C-reactive protein(CRP)(cut–off >150)is suggested to evaluate the severity of acute pancreatitis 48-72 hours after its onset.
Scoring systems including multiple criteria have been defined 30 years ago to predict the disease prognosis and severity. Among these systems are Bank, Agarwal-Pitchumoni, Ranson, Glasgow (Imrie), APACHE II, BISAP, Balthazar, and Atlanta criteria.
In addition, Japanese clinical practice guidelines for acute pancreatitis was published in 2003 in Japan, and in 2006 in English. Later on,the Japanese Ministry of Health, Labour and Welfare developed novel diagnostic criteria in 2008 and revised the acute pancreatitis severity scoring system.
Ranson criteria, which is a pancreatitis-specific scoring system, is based on the evaluation of certain clinical and laboratory findings at the time of admission and at 48th hour. It consists of a total of 11 parameters, 5 of which are measured at the time of admission, and 6 of which are measured within the first 48 hours. It is modified for ABP(Table)[34,35].Glasgow prognostic criteria including 8 parameters was defined by Imrie.
APACHE criteria, which consisted of 34 criteria, was defined in 1981.However, due to its impractical use, it was modified as APACHE II, which included 12 criteria, in 1985.The sensitivity of this scoring system to determine pancreatitis severity is 75%, whereas it has a specifity of 92%[36,37].
APACHE III consisting of 18 criteria was defined in 1991, and with the addition of obesity, APACHE-O was defined in 1996.In a metaanalysis study on obesity(BMI>30), the incidence of systemic and local complications were higher.The incidence of mortality is below 4% in patients with an APACHE II score less than 8. The incidence of mortality ranges between 11-18% in patients who have APACHE II scores of 8 or more.
Global consensus and a practicable classification system for acute pancreatitis were offered in the Atlanta Symposium in 1992. This classification provided standardisation in study reporting and communication between clinicians was improved. In time, a revision had been mandatory since some deficiencies were noticed and knowledge about the disease was improved. Atlanta criteria were renewed in 2013.This revision is not intended to be a management guideline. .
According to the Atlanta criteria which were defined in 1992, the presence of one or more of the following indicates that acute pancreatitis will have a severe course:1-A Ransonscore of 3 or high levels in the first 48 hours. 2-APACHE II score of 8 or higher at any given time.3-Single or multiple organ failure. 4-Single or multiple local complication(necrosis, pseudocyste, abcess).The main changes in the recent Atlanta criteria are:there are two phases of acute pancreatitis in the revised classification, early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis which is also the most common form is without any organ failure, local or systemic complications and usually resolves in a week. Presence of transient organ failure, local complications or exacerbation of co-morbid disease is the main considerations of moderately severe acute pancreatitis. Severe acute pancreatitis is described by persistent organ failure (more than 48 hours). Peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected) are the local complications. Standardised template for reporting CT images is also described.
BISAP;a scoring system consisting of five parameters stated below and which gained prospective value in the recent years:BUN >25 mg/dl, altered mental status, SIRS, age>60, pleural effusion.
CT and especially dynamic contrast CT gives valuable information about disease severity and prognosis in acute pancreatitis. Balthazar classification which is based CT results was defined in 1985.This classification includes the degree of pancreatic enlargement and inflammation severity, presence and amount of fluid collection and the degree of pancreatic necrosis.
Bank and Agarwal criteria
Researchers like Bank and Agarwal have also identified prognostic systems consisting of different parameters and which are known with their names.
Treatment of Acute Biliary Pancreatitis
While most of the attacks in acute pancreatic inflammation are edematous/mild acute pancreatitis that regresses in 5-7 days, necrotizing/severe acute pancreatitis that may lead to mortality may develop in approximately 20% of the cases.Therefore, all patients with acute pancreatitis should be hospitalized and given initial supportive care, their disease etiologies should be evaluated and resolved, the severity of pancreatitis should be evaluated, and advanced treatment approach should be planned in accordance with the disease severity(Figure)[7,21,22].
In all cases with acute pancreatitis, the initial treatment should include discontinuing oral intake, intravenous fluid replacement and pain management.Mild pancreatitis attack rapidly regresses with this treatment, and with regressing abdominal pain, disappearance of nausea and vomiting and normal appetite, oral intake is started again. However, if oral intake does not seem to be possible within 5-7 days, nutritional support should also be added to the treatment.
Due to inflammation, there is a significant fluid loss to third spaces such as the interstitial space, and microcirculation is altered as a result of decreasing intravascular volume. This situation both facilitates the development pancreatic necrosis and leads to systemic complications through acute renal failure and the increase in intestinal bacterial translocation.Therefore, sufficient fluid and electrolyte replacement play a key role in protection from the systemic complications of acute pancreatitis. Early oxygen support to stabilize arterial oxygen saturation over 95% and fluid resuscitation has been reported to be associated with early regression and mortality in cases of organ failure.While the rate of fluid replacement with isotoniccrystalloids and colloids, when needed, has not been established with clinical studies, the general approach recommends a rate of 250-300cc/hour and a urination rate of 0.5-1.0cc/kg/hour is aimed[50,51].
Nasogastric application is not always necessary, but is suggested in case of bowel obstruction or severe nausea-vomiting. H2 receptor blockers and PPIs should be considered for acute mucosal lesions and gastrointestinal bleedings.
Discontinuing oral intake and nutritional treatment
Nutritional support is not necessary as inflammation will be rapidly over in most of the cases. However, if oral intake does not seem to be possible within 5-7 days, enteral nutrition should also be added to the treatment.This situation is frequently observed in patients with severe acute pancreatitis, and especially enteral nutrition started within the first 48 hours of hospitalization has been reported to significantly reduce mortality in severe acute pancreatitis.Medical nutrition is recently understood and has increasing importance in patients with acute pancreatitis. Contrary to previous knowledge, preferring enteral nutrition, rather than parenteral nutrition.Microorganisms infecting the necrotising pancreatitis generally originate from bowel, and are associated with increased bacterial translocation. Therefore, enteral nutrition is the main treatment approach to ensure the integrity of intestinal epithelia, thereby ensuring mucosal barrier integrity to decrease the translocation.
Pain management is one of the steps in acute pancreatitis treatment.Especially morphine is known to increase oddi sphincter contraction and bupremorphineis recommended in Japanese guidelines, opioid agonist meperidin(petidin) is frequently used for this purpose. Nonsteriod antiinflammary drugs (NSAIDs), on the other hand, may be used additionaly for pain management in cases where narcotics have weak effect or alone in cases with mild symptoms. Albeit, the use of NSAIDs have been reported to reduce the frequency of post-ERCP pancreatitis in patients without oddi sphincter dysfunction, due to antiinflammtory effect.
Procedures targeting etiological factor
If cholangitis and extended passage disorder is suspected in patients with ABP, endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy (ERCP /ES) should be performed in the early stage. If ABP patients have gallstones, it is not recommended to treat bile duct stones with ERCP/ES. Laparoscopic cholecystectomy(LC) is suggested to be performed immediately following disease stabilization.Early cholecystectomy and ERCP reduce the recurrent ABP attacks.
LC prevents situations including recurrent ABP, cholesistitis, coledoc obstruction, cholangitis and biliary cholic. Regarding the timing of cholecystectomy, presence of complications such as severity of pancreatitis, local complications and organ failure, and their resolution is crucial. In the PONCHO study,early cholecystectomy performed in the first 72 hours was compared to cholecystectomy with a 25-30 day interval in patients with mild ABP. According to this study, the incidence of readmission and mortality were lower in patients who underwent early cholecystectomy.
Four approaches can be employed to investigate the ABP biliary tract and to treat the gallstones in the main biliary tract:A-ERCP/ES can be performed prior to the surgery; after the diagnosis and treatment of gallstones in the main biliary tract. LC should be performed. B-LC and intraoperative cholangiography(IOC), instead of ERCP, can be performed;if a gallstone is detected in the main biliary tract, the procedure can be converted to the open surgery and then coledoc exploration and gallstone treatment can be performed C- If a gallstone is detected in the main biliary tract using IOC, the procedure can be completed laparoscopically. ES should be performed either during the surgery or in the post-operative phase.D-If a gallstone is detected in the main biliary tract using IOC, coledoc exploration and gallstone treatment can be performed laparoscopically.
Antibiotic treatment and other treatments
Prophylactic antibiotic use is not suggested in cases of mild acute pancreatitis, its use in sterile necrotizing pancreatitis is controversial, because resistant bacterial or fungal infections may develop in prophylactic antibiotic use.On the other hand, the incidence of infected necrosis may reach to 40-70% in patients with necrotizing pancreatitis.As a result of the studies on this topic, 14-day ab initio antibiotic prophylaxis using broad-spectrum carbapenems, which have good penetration into the pancreas, is recommended in cases with pancreatic necrosis rates higher than 30%. If infection is suspected in cases with fever or deterioration of general condition despite antibiotic prophylaxis or if these conditions are observed in the follow-ups, bacteriological examination should be performed using pancreatic thin needle aspirationand surgical debridement should not be delayed when needed[18,58].
In most studies, the use of gabexatemesilate in acute pancreatitis did not decrease the frequency of surgical intervention and mortality, but reduced the frequency of complications.In another study,a reduction in complication frequency and mortality rates has been reported after a 7-day infusion treatment with 2400mg/day dose of gabexatemesilate.Hence, the use of protease inhibitors in severe acute pancreatitis is currently controversial.
While the ability of somatostatin and its analog octreotide to suppress the exocrine secretions of the pancreas, and therefore rest the inflamed pancreatic tissue has caused therapeutic expectations, their efficiency was not demonstrated except for a single study[61,62].Somatostatin and octreotide have been reported to reduce mortality only in severe acute pancreatitis in a single meta analysis,the current notion does not recommend their use in treatment with respect to cost-effectiveness.
Surgical treatment in acute pancreatitis
The role of surgical treatment in patients with pancreatic necrosis is still controversial. According to international consensus, surgical intervention in acute pancreatitis is only recommended for infected pancreatic necrosis[64-66].Surgical intervention should aim to remove all pancreatic tissues that cause the release of inflammatory mediators. For this purpose, various forms of necrosectomy and drainage methods, including surgical, radiological, endoscopic and minimally invasive, have been defined.
If the patient is clinically stable, surgical intervention is suitable after a 3-4 week of antibiotic therapy, decreased inflammatory reaction and reorganization of the infected region.
The method was described by Freeny in 1998, and is based on the placement of thick percutaneous drainage catheters into the infected pancreatic tissue with the aid of CT. However, it does not result in very successful outcomes, and thus, is recommended for use in removing purulent fluid only in unstable patients in intensive care, and during patient’s surgical preparation.
Endoscopic necrosectomy has found increased frequency in the treatment of pancreatic necrosis, fluid collections and pseudocysts, and has considerably high success rates. This technique has gained a place among the natural orifice endoscopic surgery(NOTES)methods. The main advantages of this method include that it does not require general anesthesia, its reproducibility, and it is minimally invasive.The major complications are bleeding, free perforation, gastric and duodenal fistules. Endoscopic ultrasonography, doppler imaging and scopy is relatively useful to prevent complications.
Minimally invasive necrosectomy
In recent years, less invasive methods have found a place as an alternative to open surgical interventions, especially in patients who do not have good overall conditions due to organ failure and comorbid diseases.In the first method; using percutaneous technique, the necrotic region is reached via nephroscope under CT, necrosectomy is performed, catheters are left for a long period for continuous irrigation, and continuous irrigation is performed with high-volume lavage. In the second method, drains with wide calibration are placed using laparoscopic necrosectomy and direct view.
Mild ABP does not leave clinically significant sequel in the long term.The incidence of late-term complications, such as delayed collections, pancreatic pseudocyst, biliary structure, persistent pancreatic fistula, gastrointestinal fistula, incisional hernia, pancreatic exocrine insufficiency and diabetes mellitus, may reach up to 60% in mild ABP.Therefore, long-term follow-up is required to monitor and manage the development of these late complications.
Endoscopic and Interventional Approaches in ABP
The suitable timing of cholecystectomy in ABP depends on the clinical course of the disease.In severe ABP with local and systemic complications, it may be recommended to postpone cholecystectomy after the resolution of these complications. The timing of cholecystectomy in mild ABPs which do not have local and systemic complications is controversial. While some studies recommend it at the time of admission [70,72],others recommend it two, three or four weeks after discharge from the hospital[72-74].
Other strategies, in addition to general precautions and medical treatment, are needed to improve the prognosis. Endoscopic treatment is one of these strategies. However, there is an ongoing discussion on the effect of early ERCP, which is performed between 24-72 hours, and sphincterotomy on the prognosis in cases with ABP. Two metaanalysis on this topic have been published. One of these metaanalyses concluded that early ERCP had no positive effect on complication and mortality in mild or severe pancreatitis, whereas the other metaanalysisconcluded that early ERCP and sphincterotomy reduced complications rates in severe pancreatitis[76,77].The latest study on this topic belongs to the Netherlands acute pancreatitis research group.In this prospective, controlled study with 153 cases, the incidence of complications were lower in patients who had severe ABP and cholestatis(bilirubin>2.3 mg/dl and/or diameter of the common bile duct>8 mm) and who underwent early ERCP and sphincterotomy.In acute pancreatitis cases without cholestatis, the incidence of complications was similar between patients who received conservative treatment and patients who underwent ERCP. Common bile duct stoneshave been detected in approximately 50% of the cases with/without cholestatis, and similar incidence rates have been determined.In a study by Yeung et al., which involved 172 patients, routine ERCP was not suggested for mild ABP patients.
Early ERCP and sphincterotomy may reduce severe pancreatitis-dependent complication rates in selected cases. For the moment, ERCP and sphincterotomy should be recommended for cases with cholangitis, mild or severe pancreatitis with common bile duct stones determined by non-invasive methods, and severe pancreatitis with cholestatis findings, which do or do not have common bile duct stones. Differential diagnosis of cholangitis and pancreatitis can be difficultin patients who have severe pancreatitis and SIRS. In these patients, every effort including methods such as MRCP and EUS should be performed to demonstrate biliary obstruction before ERCP.First MRCP, and then EUScan be performed to choose patients for ERCP[82,83].Pancreas, axtrahepatic biliary tracts and ampullary region can be evaluated in detail using EUS.
When bilayer drainage cannot be performed using ERCP/ES, endoscopic nasobiliary drainage or percutaneous transhepatic gallbladder drainage procedures can be performed alternatively.
In conclusion, the pathogenesis of ABP has not been fully elucidated and several theories have been suggested. Novel laboratory methods and scoring systems have been suggested for both diagnosis and to predict disease severity, and research on these topics is still in progress. Novel therapeutic approaches are also suggested with technological developments.
The authors declare that they have no competing interests.
1. Dikicier E, Ozmen M.Pathophysiology of Acute Pancreatitits and Experimental Pancreatitis. Turkiye Klinikleri J Gen Surg-Special Topics 2011;4(1):5-15.
2. Papachristou GI, Clermont G, Sharma A, Yadav D, Whitcomb DC. Risk and markers of severe acute pancreatitis. Gastroenterol Clin North Am 2007;36:277-96.
3. Bakker OJ, van Santvoort HC, Hagenaars JC, Besselink MG, Bollen TL, Gooszen HG, et al. Dutch Pancreatitis Study Group. Timing of cholecystectomy after mild biliary pancreatitis. Br J Surg 2011;98:1446-54.
4. Sekimoto M, Takada T, Kawarada Y, Hirata K, Mayumi T, Yoshida M, et al. JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis. J Hepatobiliary Pancreat Surg 2006;13:10-24.
5. Opie EL. On the relation of chronic interstitial pancreatitis to the islands of langerhans and to diabetes melutus. J Exp Med 1901;15:397-428.
6. Attasaranya S, Abdel Aziz AM, Lehman GA.Endoscopic management of acute and chronic pancreatitis. Surg Clin North Am 2007;87:1379-402.
7. Koizumi M, Takada T, Kawarada Y, Hirata K, Mayumi T, Yoshida M, et al. JPN Guidelines for the management of acute pancreatitis: diagnostic criteria for acute pancreatitis. J Hepatobiliary Pancreat Surg 2006;13:25-32.
8. Yurumez Y. Akut pankreatitlerde klinik bulgular ve tanı. Turkiye Klinikleri J Gen Surg-Special Topics 2011;4:29-34.
9. Cappell MS. Acute pancreatitis: etiology, clinical presentation, diagnosis, and therapy. Med Clin North Am 2008;92:889-923.
10. Kiriyama S, Gabata T, Takada T, Hirata K, Yoshida M, Mayumi T, et al. New diagnostic criteria of acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17:24-36.
11. Shah AM, Eddi R, Kothari ST, Maksoud C, DiGiacomo WS, Baddoura W. Acute pancreatitis with normal serum lipase: a case series. JOP 2010;5:369-72.
12. Lippi G, Valentino M, Cervellin G. Laboratory diagnosis of acute pancreatitis: in search of the Holy Grail. Crit Rev Clin Lab Sci 2012;49:18-31.
13. Carroll JK, Herrick B, Gipson T, Lee SP. Acute pancreatitis: diagnosis, prognosis, and treatment. Am Fam Physician 2007;15:1513-20.
14. Al-Bahrani AZ, Ammori BJ. Clinical laboratory assessment of acute pancreatitis. Clin Chim Acta 2005;362:26-48.
15. Sigounas DE, Tatsioni A, Christodoulou DK, Tsianos EV, Ioannidis JP. New prognostic markers for outcome of acute pancreatitis: overview of reporting in 184 studies. Pancreas 2011;40:522-32.
16. Akpınar G, Kasap M, Cantürk Z, Cantürk NZ. What is proteomics? Proteomics in thyroid diseases research. Endokrinolojide Diyalog 2011;8: 166-76.
17. Kim DH, Pickhardt PJ. Radiologic assessment of acute and chronic pancreatitis. Surg Clin North Am 2007;87:1341-58.
18. Banks PA, Freeman ML. Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101:2379-400.
19. Diehl AK, Holleman DR Jr, Chapman JB, Schwesinger WH, Kurtin WE. Gallstone size and risk of pancreatitis. Arch Intern Med 1997;157:1674-78.
20. Soto JA, Barish MA, Alvarez O, Medina S. Detection of choledocholithiasis with MR cholangiography: comparison of three-dimensional fast spin-echo and single- and multisection half-Fourier rapid acquisition with relaxation enhancement sequences. Radiology 2000;215:737-45.
21. Alexakis N, Neoptolemos JP. Algorithm for the diagnosis and treatment of acute biliary pancreatitis. Scand J Surg 2005;94:124-29.
22. Kimura Y, Arata S, Takada T, Hirata K, Yoshida M, Mayumi T, et al. Gallstone-induced acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17:60-9.
23. Gislason H, Horn A, Hoem D, Andrén-Sandberg A, Imsland AK, Søreide O, et al. Acute pancreatitis in Bergen, Norway. A study on incidence, etiology and severity. Scand J Surg 2004;93:29-33.
24. Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acute pancreatitis. N Engl J Med 1992;27:589-93.
25. Jüngst C, Kullak-Ublick GA, Jüngst D. Gallstone disease: Microlithiasis and sludge. Best Pract Res Clin Gastroenterol 2006;20:1053-62.
26. Lerch MM, Saluja AK, Rünzi M, Dawra R, Saluja M, Steer ML. Pancreatic duct obstruction triggers acute necrotizing pancreatitis in the opossum. Gastroenterology 1993;104:853-61.
27. Wang GJ, Gao CF, Wei D, Wang C, Ding SQ. Acute pancreatitis: etiology and common pathogenesis. World J Gastroenterol 2009;28:1427-30.
28. Johnson C, Lévy P. Detection of gallstones in acute pancreatitis: when and how? Pancreatology 2010;10:27-32.
29. Dholakia K, Pitchumoni CS, Agarwal N. How often are liver function tests normal in acute biliary pancreatitis? J Clin Gastroenterol 2004;38:81-3.
30. Acosta JM, Ledesma CL.Gallstone migration as a cause of acute pancreatitis. N Engl J Med 1974;28:484-7.
31. McCutcheon AD. A fresh approach to the pathogenesis of pancreatitis. Gut 1968;9:296-310.
32. Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology 1990;174:331-6.
33. Wada K, Takada T, Hirata K, Mayumi T, Yoshida M, Yokoe M, et al. Treatment strategy for acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17:79-86
34. Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974;139:69-81.
35. Brunicardi FC( Editor-in Chief). Schwartz’s Principles of Surgery. Chapter 33 Pancreas Fisher WE, Andersen DK, Jr. Bell RH, Saluja AK, Brunicardi FC. Mc Graw Hill Medical. Houston, Texas. Ninth Edition. 2010. p: 1167-1243.
36. Larvin M, McMahon MJ. APACHE-II score for assessment and monitoring of acute pancreatitis. Lancet 1989;22:201-5.
37. Brisinda G, Maria G, Ferrante A, Civello IM. Evaluation of prognostic factors in patients with acute pancreatitis. Hepatogastroenterology 1999;46:1990-7.
38. Johnson CD, Toh SK, Campbell MJ. Combination of APACHE-II score and an obesity score (APACHE-O) for the prediction of severe acute pancreatitis. Pancreatology 2004;4:1-6.
39. Banks PA, Freeman ML. Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101:2379-2400.
40. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62(1):102-11.
41. Bradley EL 3rd. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch Surg 1993;128(5):586-90.
42. Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut 2008;57:1698-703.
43. Bank S, Wise L, Gersten M. Risk factors in acute pancreatitis. Am J Gastroenterol 1983;78:637-40.
44. Agarwal N, Pitchumoni CS. Simplified prognostic criteria in acute pancreatitis. Pancreas 1986;1:69-73.
45. Wada K, Takada T, Hirata K, Mayumi T, Yoshida M, Yokoe M, et al. Treatment strategy for acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17:79-86.
46. Forsmark CE, Baillie J. AGA Institute Clinical Practice and Economics Committee; AGA Institute Governing Board. AGA Institute technical review on acute pancreatitis. Gastroenterology 2007;132:2022-44.
47. Gianotti L, Meier R, Lobo DN, Bassi C, Dejong CH, Ockenga J, et al. ESPEN Guidelines on Parenteral Nutrition: pancreas. Clin Nutr 2009;28:428-35.
48. Stevens T, Parsi MA, Walsh RM. Acute pancreatitis: problems in adherence to guidelines. Cleve Clin J Med 2009;76:697-704.
49. Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut 2004;53:1340-4.
50. Muddana V, Whitcomb DC, Papachristou GI. Current management and novel insights in acute pancreatitis. Expert Rev Gastroenterol Hepatol 2009;3:435-44.
51. American Gastroenterological Association (AGA) Institute on “Management of Acute Pancreatits” Clinical Practice and Economics Committee; AGA Institute Governing Board. AGA Institute medical position statement on acute pancreatitis. Gastroenterology 2007;132:2019-21.
52. Petrov MS, Pylypchuk RD, Uchugina AF. A systematic review on the timing of artificial nutrition in acute pancreatitis. Br J Nutr 2009;101:787-93.
53. Spanier BW, Bruno MJ, Mathus-Vliegen EM. Enteral nutrition and acute pancreatitis: a review. Gastroenterol Res Pract 2011;2011. pii: 857949.
54. Senol A, Saritas U, Demirkan H. Efficacy of intramuscular diclofenac and fluid replacement in prevention of post-ERCP pancreatitis. World J Gastroenterol 2009;28:3999-4004.
55. Nguyen GC, Rosenberg M, Chong RY, Chong CA. Early cholecystectomy and ERCP are associated with reduced readmissions for acute biliary pancreatitis: a nationwide, population-based study. Gastrointest Endosc 2012;75:47-55.
56. Bouwense SA, Besselink MG, van Brunschot S, Bakker OJ, van Santvoort HC, Schepers NJ, et al.( Collaborators 42); Dutch Pancreatitis Study Group. Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial. Trials 2012;26:225-35.
57. Isenmann R, Schwarz M, Rau B, Trautmann M, Schober W, Beger HG. Characteristics of infection with Candida species in patients with necrotizing pancreatitis. World J Surg 2002;26:372-6.
58. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet. 2008;12:143-52.
59. Valderrama R, Pérez-Mateo M, Navarro S, Vázquez N, Sanjosé L, Adrián MJ, et al. Multicenter double-blind trial of gabexate mesylate (FOY) in unselected patients with acute pancreatitis. Digestion 1992;51:65-70.
60. Chen HM, Chen JC, Hwang TL, Jan YY, Chen MF. Prospective and randomized study of gabexate mesilate for the treatment of severe acute pancreatitis with organ dysfunction. Hepatogastroenterology 2000;47:1147-50.
61. Bang UC, Semb S, Nojgaard C, Bendtsen F. Pharmacological approach to acute pancreatitis. World J Gastroenterol. 2008; 21:2968-76.
62. Uhl W, Büchler MW, Malfertheiner P, Beger HG, Adler G, Gaus W. A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis. Gut 1999;45:97-104.
63. Andriulli A, Leandro G, Clemente R, Festa V, Caruso N, Annese V, et al. Meta-analysis of somatostatin, octreotide and gabexate mesilate in the therapy of acute pancreatitis. Aliment Pharmacol Ther 1998;12:237-45.
64. De Rai P, Zerbi A, Castoldi L, Bassi C, Frulloni L, Uomo G, et al. (Collaborator 120). Surgical management of acute pancreatitis in Italy: lessons from a prospective multicentre study. HPB (Oxford) 2010;12:597-604.
65. Yetim İ, Özkan OV, Diner G, Yılmaz A, Gökçe C, Kaya H. Hipertrigliseridemi sonucu gelişen nekrotizan pankreatit: Olgu sunumu. J Clin Anal Med 2011;2(3):124-6.
66. Yaylak F, Zeybek N, Altınel Ö, Çelik A, Yuruker Ss. Hepato-Pankreato-Bilier Komplikasyonların nadir bir nedeni olarak Ascaris Lumbricoides: İki vakanın sunumu ve kısa bir literatür derlemesi. J Clin Anal Med 2011; 2(3):124-6.
67. Gouzi JL, Bloom E, Julio C, Labbé F, Sans N, el Rassi Z, et al. Percutaneous drainage of infected pancreatic necrosis: an alternative to surgery. Chirurgie 1999;124:31-7.
68. Mathew A, Biswas A, Meitz KP. Endoscopic necrosectomy as primary treatment for infected peripancreatic fluid collections (with video). Gastrointest Endosc 2008;68:776-82.
69. Bucher P, Pugin F, Morel P. Minimally invasive necrosectomy for infected necrotizing pancreatitis. Pancreas 2008;36:113-9.
70. Parekh D. Laparoscopic-assisted pancreatic necrosectomy: A new surgical option for treatment of severe necrotizing pancreatitis. Arch Surg 2006;141:895-902.
71. Alimoglu O, Ozkan OV, Sahin M, Akcakaya A, Eryilmaz R, Bas G. Timing of cholecystectomy for acute biliary pancreatitis: outcomes of cholecystectomy on first admission and after recurrent biliary pancreatitis. World J Surg 2003;27:256-9.
72. van Baal MC, Besselink MG, Bakker OJ, van Santvoort HC, Schaapherder AF, Nieuwenhuijs VB, et al. Dutch Pancreatitis Study Group. Timing of cholecystectomy after mild biliary pancreatitis: a systematic review. Ann Surg 2012;255:860-6.
73. Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch PG, et al. International Association of Pancreatology. IAP Guidelines for the Surgical Management of Acute Pancreatitis. Pancreatology 2002;2:565-73.
74. Toouli J, Brooke-Smith M, Bassi C, Carr-Locke D, Telford J, Freeny P, et al. Working Party of the Program Commitee of the Bangkok World Congress of Gastroenterology 2002. Guidelines for the management of acute pancreatitis. J Gastroenterol Hepatol 2002 ;17 (Suppl):S15-39.
75. van Geenen EJ, Mulder CJ, van der Peet DL, Fockens P, Bruno MJ. Endoscopic treatment of acute biliary pancreatitis: a national survey among Dutch gastroenterologists. Scand J Gastroenterol 2010;45:1116-20.
76. Petrov MS, van Santvoort HC, Besselink MG, van der Heijden GJ, van Erpecum KJ, Gooszen HG. Early endoscopic retrograde cholangiopancreatography versus conservative management in acute biliary pancreatitis without cholangitis: a meta-analysis of randomized trials. Ann Surg 2008;247:250-7.
77. Sharma VK, Howden CW. Metaanalysis of randomized controlled trials of endoscopic retrograde cholangiography and endoscopic sphincterotomy for the treatment of acute biliary pancreatitis. Am J Gastroenterol 1999;94:3211-4.
78. van Santvoort HC, Besselink MG, de Vries AC, Boermeester MA, Fischer K, Bollen TL, et al. Dutch Acute Pancreatitis Study Group. Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: a prospective multicenter study. Ann Surg 2009;250(1):68-75.
79. Yeung YP, Lo SF, Yip AW. Role of ERCP in the management of predicted mild acute biliary pancreatitis. Asian J Surg 2003;26:197-201.
80. Kapetanos DJ. ERCP in acute biliary pancreatitis. World J Gastrointest Endosc. 2010 16;2(1):25-8.
81. Fusaroli P, Kypraios D, Caletti G, Eloubeidi MA. Pancreatico-biliary endoscopic ultrasound: a systematic review of the levels of evidence, performance and outcomes. World J Gastroenterol 2012;28:4243-56.
82. Romagnuolo J, Currie G. Calgary Advanced Therapeutic Endoscopy Center study group. Noninvasive vs. selective invasive biliary imaging for acute biliary pancreatitis: an economic evaluation by using decision tree analysis. Gastrointest Endosc 2005;61:86-97.
83. Okan I, Bas G, Sahin M, Alimoglu O, Eryilmaz R, Ozkan OV, et al. Diagnostic value of MRCP in biliary pancreatitis: result of long-term follow-up. Acta Chir Belg 2012;112:359-64.