Schematic presentation of the alternative treatment options and their outcomes is depicted in Figure 1.
Patients fit for surgery
Index cholecystectomy: The British Society of Gastroenterology guidelines underline that, in patients with severe acute pancreatitis, cholecystectomy should be postponed until all signs of systemic disorders have resolved. Furthermore, the American College of Gastroenterology guidelines state that, in order to avoid contamination in patients with necrotizing biliary acute pancreatitis, cholecystectomy should be delayed until the inflammatory process has subsided, and fluid collections have resolved or become stable.
An increased incidence of contaminated collections is observed when performing early cholecystectomy after moderate to severe pancreatitis. Cholecystectomy is typically delayed in patients with severe acute pancreatitis until a later time during index admission or after discharge, even weeks or months after the pancreatitis episode, or, if pancreatic necrosis is present, cholecystectomy can be performed along with necrosectomy[13,21,22,51].
Initial ERCP and sphincterotomy: In patients who did not undergo cholecystectomy, the risk of recurrent pancreatitis was significant, 8.2% in patients who had ERCP and 17.1% in patients with no intervention, after a median follow-up of 2.3 years. Despite the fact that ERCP substantially prevents recurrent pancreatitis, it does not prevent acute cholecystitis and biliary colic. The value of ERCP in patients with acute biliary pancreatitis and concomitant cholangitis is well recognized[5,6,25,33], whereas, the role and timing of ERCP with sphincterotomy in patients with predicted severe biliary pancreatitis without cholangitis or a high suspicion of a persistent common bile duct stone remains subject to debate.
A recurrent rate of acute biliary pancreatitis, between 0% and 7% was observed in patients who had ERCP and sphincterotomy at index admission but did not receive cholecystectomy[8,19,47,48,50,52]. The risk of recurrent pancreatitis was reduced after sphincterotomy[7,9,19,48,49]. There is ample evidence to support the belief that sphincterotomy at index admission with interval cholecystectomy is a safe and accurate practice and is considered an alternative to index cholecystectomy in patients with severe biliary pancreatitis[13,21,47,48,50,53]. In a retrospective study, no readmissions with recurrent acute pancreatitis or biliary symptoms were observed in patients with severe biliary pancreatitis that had ERCP and sphincterotomy as definitive treatment in patients not fit for cholecystectomy, during median follow-up of 3.1 years. A second retrospective study including patients with moderately severe pancreatitis reported that, after ERCP, no episodes of recurrent pancreatitis were detected while waiting for interval cholecystectomy. Interval laparoscopic cholecystectomy has the potential of recurrent biliary events and additional hospital stay related to a second admission[22,45]. Wilson et al concluded that patients with moderate to severe acute biliary pancreatitis should undergo interval cholecystectomy at a later time, weeks or months after recovering from the initial episode, depending on the patients’ clinical condition, provided the patient underwent ERCP and sphincterotomy at index admission. A large population-based study provided evidence that cholecystectomy and ERCP at index admission were associated with significantly reduced 12-mo readmission rates for acute biliary pancreatitis.
Initial interval cholecystectomy: Patients with no fluid collections can undergo cholecystectomy after the inflammatory process has subsided and the clinical condition has improved. Laparoscopic cholecystectomy at index admission is technically demanding and, due to the inflammatory process, it is frequently converted to an open procedure. Interval cholecystectomy probably increases the success rate of laparoscopic cholecystectomy and makes it safer for patients with decreased morbidity[21,24]. Although interval cholecystectomy allows the inflammatory response to resolve, it has been demonstrated that it cannot lessen severe adhesions, elude difficult dissection of the cystic duct and artery in Calot’s triangle, or avoid bleeding, thus resulting in a prolonged operating time.
As pseudocyst formation may occur in patients recovering from an acute episode of severe biliary pancreatitis, cholecystectomy can be combined with procedures for internal drainage of pseudocysts if they do not resolve after 6 wk, thus avoiding a possible second procedure to drain a pseudocyst. Timing of interval cholecystectomy varies among studies and it has been reported that patients with severe biliary pancreatitis underwent interval cholecystectomy within 6 mo. In a multicenter study including 523 patients with biliary pancreatitis, fewer operative complications during cholecystectomy were observed between 4 and 7 wk after discharge, and higher at index admission up to 2 wk after discharge. Since delaying surgery further than 2 wk after discharge has no apparent unfavorable effect, and delaying definitive management after 12 wk has no prominent advantage, definitive management within 3 mo of admission may decrease recurrent biliary events, readmission rates and operative risk. In patients recovering from an episode of acute pancreatitis and a small pseudocyst with mild symptoms, cholecystectomy can be delayed for a further 3 mo, since spontaneous resolution of the pseudocyst may still occur.
Management of pseudocysts and walled-off necrosis according to management plans: Most of the fluid collections generally resolve spontaneously without the need for further intervention, but 5%-16% of patients with severe acute pancreatitis will develop a pseudocyst > 4 wk after onset of pancreatitis[57,58]. The prevalence in biliary pancreatitis is 6%-8%. A pseudocyst will also develop in 8% of patients who have undergone necrosectomy. In a recent prospective multicenter study including 302 patients with acute pancreatitis, pancreatic pseudocysts developed in 6.3% of patients after 4-6 wk. A decrease in size or spontaneous resolution of pseudocysts was observed in an elevated percentage of patients that increased to 84.2% with conservative management.
Italian Association for the study of the Pancreas consensus guidelines on severe acute pancreatitis point out that size < 4 cm is a predictor of spontaneous resolution. Furthermore, a prospective study including 369 patients found that prognostic factors for spontaneous resolution of pancreatic pseudocysts after an episode of acute pancreatitis were mild or presented no symptoms and a maximum pseudocyst diameter < 4 cm. A large pseudocyst size itself does not necessitate drainage, although pseudocysts > 6 cm persisting for > 6 wk tend to be symptomatic and have a low likelihood of resolution[11,12]. The American College of Radiology appropriateness criteria in 2009 recommend drainage of complicated pseudocysts ≥ 5 cm that are rapidly enlarging, obstructing, and infected. According to the American College of Gastroenterology guidelines of 2013, asymptomatic pseudocysts and pancreatic or extrapancreatic necrosis regardless of size, location, or extension do not require intervention. The asymptomatic patient is a controversial issue. A wait-and-see policy can be adopted in patients with asymptomatic pseudocysts or minimally symptomatic patients, even after the 6 wk that are required for maturation of a pseudocyst[61,62]. Indications for intervention are symptomatic pseudocysts with persistent pain, nausea and vomiting, or complications, such as infection, gastric or duodenal outlet obstruction, biliary obstruction, rupture and rapidly enlarging cysts[16,63].
Integrity of the main pancreatic duct and awareness of the available techniques help in applying the most appropriate intervention, among endoscopic, surgical and image-guided percutaneous techniques. Pancreatic ductal anatomy is clearly associated with the outcome of pseudocysts managed by percutaneous drainage, with favorable outcomes in patients with normal ducts, and satisfactory outcomes in patients with stricture but no cyst-duct communication. Percutaneous drainage is associated with a high recurrence rate and risk of secondary infection and formation of a pancreatic fistula; thus, it is best applied to infected pseudocysts or patients not suitable for an endoscopic or surgical procedure. Percutaneous drainage alone is associated with therapeutic rates ranging from 14% to 32%, therefore it is usually performed as a temporary measure before endoscopic or surgical management[17,65].
Successful drainage can be achieved with the endoscopic approach in 82%-100% of pancreatic pseudocysts, with complications ranging from 5% to 16% and recurrence rates up to 18%[16,66]. Due to high success rates and low complications rates, the endoscopic approach emerges as the most efficient method. Transpapillary drainage has been used for pancreatic pseudocysts communicating with the main pancreatic duct but it is associated with ERCP-related complications, contamination of the pseudocyst, and insufficient drainage of large cysts[16,61]. Pseudocysts > 4 cm require transmural drainage, preferably with EUS guidance but conventional endoscopy also offers good results. Transmural drainage has gradually become the preferred therapeutic approach for managing pseudocysts, including the advantages of cystogastrostomy or cystoduodenostomy (internal drainage). A recent multicenter retrospective study found that transpapillary drainage of pseudocysts in patients undergoing EUS-guided transmural drainage added no benefit to outcomes and adversely affected resolution of the pseudocyst.
Transmural drainage can be carried out either by direct endoscopy or by EUS guidance. Endoscopy by EUS guidance is increasingly used in particular for pseudocysts in which there is no definitive luminal bulge, or when managing patients with portal hypertension or coagulopathy. A recent systematic review reported mean technical and clinical success rates of 97% and 90%, respectively, mean overall recurrence rate of 8%, and overall complication rate of 17% for EUS-guided drainage. A meta-analysis comparing EUS-guided drainage with conventional transmural drainage for pseudocyst found that technical success rate was significantly higher for EUS-guided drainage but not superior to conventional transmural drainage in terms of short- and long-term success, and overall complications were similar in both groups. A randomized trial comparing patients undergoing EUS-guided drainage with conventional transmural drainage for pseudocysts found a technical success rate of 100% and 33%, respectively. A second randomized trial also found a higher technical success rate for patients undergoing EUS-guided drainage than for conventional endoscopic drainage (94% vs 72%). While high clinical success rates have been reported when draining pseudocysts with endoscopic procedures, clinical success rates for walled-off necrosis are relatively poor due to the presence of solid material. Multiple transluminal gateway treatment is suggested for walled-off necrosis, thus avoiding the need for surgery or endoscopic necrosectomy or other more complex procedures. Endoscopic procedures for pseudocyst drainage are technically feasible only if access to the pseudocyst through the gastric or duodenal wall can be achieved; at present performance of an endoscopic cystjejunostomy is not possible. Patients requiring more complex management of their pseudocyst are not candidates for endoscopic procedures. Another limitation of the endoscopic approach is the inability to perform an additional cholecystectomy when necessary, as patients with biliary pancreatitis require open or laparoscopic cholecystectomy.
Surgical cystogastrostomy or cystojejunostomy has been the traditional approach for pseudocyst management and is still the preferred treatment in most centers with a success rate of 94%-99%[4,74]. Open or laparoscopic surgical drainage should be applied after failure of endoscopic methods, for recurrence after a successful endoscopic drainage, and in patients who do not meet the criteria for endoscopic or percutaneous drainage. Moreover, percutaneous and endoscopic techniques, if not therapeutic, can serve as a bridge to surgery and improve patients’ local and general condition. Laparoscopy is a minimally invasive method that achieves sufficient internal drainage and debridement of necrotic tissue, with good results and minimal morbidity. In a large series on laparoscopic cystogastrostomy, the authors conclude that laparoscopy has a significant role in the surgical management of pseudocysts, with favorable outcomes. A retrospective study and a randomized trial, both by Varadarajulu et al[74,76], comparing EUS-guided drainage with open surgical cystogastrostomy found no significant difference in pseudocyst recurrence between the two groups. A drawback of these studies is the implementation of open surgery.
In patients with pseudocysts who have recovered from an acute episode of moderate to severe biliary pancreatitis, interval cholecystectomy should be delayed until the pseudocyst resolves. If it persists for > 6 wk, operative pseudocyst drainage can be performed safely at this time with concurrent cholecystectomy, thus minimizing the risk for a second interventional procedure.