Pathophysiology of severe gallstone pancreatitis:A new paradigm

Severe gallstone pancreatitis(GSP)refractory to maximum conservative therapy has wide clinical variations,and its pathophysiology remains controversial.This Editorial aimed to investigate the pathophysiology of severe disease based on Opie’s theories of obstruction,the common channel,and duodenal reflux and describe its types.Severe GSP might be a hybrid disease with pathology polarized between acute cholangitis with mild pancreatitis(biliary type)and necrotizing pancreatitis uncomplicated with biliary tract disease(pancreatic type),in which hepatobiliary and pancreatic lesion severity is inversely related to the presence or absence of impacted ampullary stones.Severe GSP is caused by stones that are persistently impacted at the ampulla with biliopancreatic obstruction(biliary type),and probably,stones that are either temporarily lodged at the duodenal orifice or passed into the duodenum,thereby permitting reflux of bile or possible duodenal contents into the pancreas(pancreas type).When the status of the stones and the presence or absence of impacted ampullary stones with biliopancreatic obstruction are determined,the clinical course and outcome can be predicted.Gallstones represent the main cause of acute pancreatitis globally,and clinicians are expected to encounter GSP more often.Awareness of the etiology and pathogenesis of severe disease is mandatory.

Evaluating the accuracy of American Society for Gastrointestinal Endoscopy guidelines in patients with acute gallstone pancreatitis with choledocholithiasis

BACKGROUND Acute gallstone pancreatitis(AGP) is the most common cause of acute pancreatitis(AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gastrointestinal Endoscopy(ASGE) suggested a management algorithm based on probability for choledocholithiasis, recommending additional imaging for patients at intermediate risk and endoscopic retrograde cholangiopancreatography(ERCP) for patients at high risk of choledocholithiasis. In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high risk for choledocholithiasis. Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis.AIM To determine compliance with ASGE guidelines, assess outcomes, and compare 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in AGP.METHODS We conducted a retrospective cohort study of 882 patients admitted with AP to a single tertiary care center from 2008-2018. AP was diagnosed using revised Atlanta criteria and AGP was defined as the presence of gallstones on imaging or with cholestatic pattern of liver injury in the absence of another cause. Patients with chronic pancreatitis and pancreatic malignancy were excluded as were those who went directly to cholecystectomy prior to assessment for choledocholithiasis. Patients were assigned low, intermediate or high risk based on ASGE guidelines. Our primary outcomes of interest were the proportion of patients in the intermediate risk group undergoing magnetic resonance cholangiopancreatography(MRCP) first and the proportion of patients in the high risk group undergoing ERCP directly without preceding imaging. Secondary outcomes of interest included outcome differences based on if guidelines were not adhered to. We then evaluated the diagnostic accuracy of 2019 in comparison to the 2010 ASGE criteria for patients with suspected choledocholithiasis. We performed the t test or Wilcoxon rank sum test, as appropriate, to analyze if there were outcome differences based on if guidelines were not adhered to. Kappa coefficients were calculated to measure the degree of agreement between pairs of variables.RESULTS In this cohort, we identified 235 patients with AGP of which 79 patients were excluded as they went directly to surgery for cholecystectomy without prior MRCP or ERCP. Of the remaining 156 patients, 79 patients were categorized as intermediate risk and 77 patients were high risk for choledocholithiasis according to the 2010 ASGE guidelines. Among 79 intermediate risk patients, 54(68%) underwent MRCP first whereas 25 patients(32%) went directly to ERCP. For the 54 patients with intermediate risk who had MRCP first, 36 patients had no choledocholithiasis while 18 patients had evidence of choledocholithiasis prompting ERCP. Of these patients, ERCP confirmed stone disease in 11 patients. Of the 25 intermediate risk patients who directly underwent ERCP, 18 patients had stone disease. One patient with a normal ERCP developed post ERCP pancreatitis. Patients undergoing MRCP in this group had a significantly longer length of stay(5.0 vs 4.0 d, P = 0.02). In the high risk group, 64 patients(83%) had ERCP without preceding imaging, of which, 53 patients had findings consistent with choledocholithiasis, of which 13 patients(17%) underwent MRCP before ERCP, all of which showed evidence of stone disease. Furthermore, all of these patients ultimately had an ERCP, of which 8 patients had evidence of stones and 5 had normal examination.RESULTS Our cohort also demonstrated that 58% of all 156 patients with AGP had confirmed choledocholithiasis(79% of the high risk group and 37% of the intermediate group when risk was assigned based on the 2010 ASGE guidelines). When the updated 2019 ASGE guidelines were applied instead of the original 2010 guidelines, there was moderate agreement between the 2010 and 2019 guidelines(kappa = 0.46, 95%CI: 0.34-0.58). Forty-two of 77 patients were still deemed to be high risk and 35 patients were downgraded to intermediate risk. Thirty-five patients who were originally assigned high risk were reclassified as intermediate risk. For these 35 patients, 26 patients had ERCP findings consistent with choledocholithiasis and 9 patients had a normal examination. Based on the 2019 criteria, 9/35 patients who were downgraded to intermediate risk had an unnecessary ERCP with normal findings(without a preceding MRCP).CONCLUSION Two-thirds in intermediate risk and 83% in high risk group followed ASGE guidelines for choledocholithiasis. One intermediate-group patient with normal ERCP had post-ERCP AP, highlighting the risk of unnecessary procedures.

Proposal of the term “gallstone cholangiopancreatitis” to specify gallstone pancreatitis that needs urgent endoscopic retrograde cholangiopancreatography

Opie’s“pancreatic duct obstruction”and“common channel”theories are generally accepted as explanations of the mechanisms involved in gallstone acute pancreatitis(AP).Common channel elucidates the mechanism of necrotizing pancreatitis due to gallstones.For pancreatic duct obstruction,the clinical picture of most patients with ampullary stone impaction accompanied by biliopancreatic obstruction is dominated by life-threatening acute cholangitis rather than by AP,which clouds the understanding of the severity of gallstone AP.According to the revised Atlanta classification,it is difficult to consider these clinical features as indications of severe pancreatitis.Hence,the term“gallstone cholangiopancreatitis”is suggested to define severe disease complicated by acute cholangitis due to persistent ampullary stone impaction.It incorporates the terms“cholangitis”and“gallstone pancreatitis.”“Cholangitis”refers to acute cholangitis due to cholangiovenous reflux through the foci of extensive hepatocyte necrosis reflexed by marked elevation in transaminase levels caused by persistent ampullary obstruction.“Gallstone pancreatitis”refers to elevated pancreatic enzyme levels consequent to pancreatic duct obstruction.This pancreatic lesion is characterized by minimal or mild inflammation.Gallstone cholangiopancreatitis may be valuable in clinical practice for specifying gallstone AP that needs urgent endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy.

Early vs late cholecystectomy in mild gall stone pancreatitis: Anupdated meta-analysis and review of literature

BACKGROUND Gallstone pancreatitis is one of the most common causes of acute pancreatitis.Cholecystectomy remains the definitive treatment of choice to prevent recurrence.The rate of early cholecystectomies during index admission remains low due toperceived increased risk of complications.AIMTo compare outcomes including length of stay, duration of surgery, biliarycomplications, conversion to open cholecystectomy, intra-operative, and postoperativecomplications between patients who undergo cholecystectomy duringindex admission as compared to those who undergo cholecystectomy thereafter.METHODSStatistical Method: Pooled proportions were calculated using both Mantel-Haenszel method (fixed effects model) and DerSimonian Laird method (randomeffects model).RESULTSInitial search identified 163 reference articles, of which 45 were selected andreviewed. Eighteen studies (n = 2651) that met the inclusion criteria were includedin this analysis. Median age of patients in the late group was 43.8 years while thatin the early group was 43.6. Pooled analysis showed late laparoscopiccholecystectomy group was associated with an increased length of stay by 88.96 h(95%CI: 86.31 to 91.62) as compared to early cholecystectomy group. Pooled riskdifference for biliary complications was higher by 10.76% (95%CI: 8.51 to 13.01) in the late cholecystectomy group as compared to the early cholecystectomy group.Pooled analysis showed no risk difference in intraoperative complications [riskdifference: 0.41%, (95%CI: -1.58 to 0.75)], postoperative complications [riskdifference: 0.60%, (95%CI: -2.21 to 1.00)], or conversion to open cholecystectomy[risk difference: 1.42%, (95%CI: -0.35 to 3.21)] between early and latecholecystectomy groups. Pooled analysis showed the duration of surgery to beprolonged by 39.11 min (95%CI: 37.44 to 40.77) in the late cholecystectomy groupas compared to the early group.CONCLUSIONIn patients with mild gallstone pancreatitis early cholecystectomy leads to shorterhospital stay, shorter duration of surgery, while decreasing the risk of biliarycomplications. Rate of intraoperative, post-operative complications and chances ofconversion to open cholecystectomy do not significantly differ whethercholecystectomy was performed early or late.