Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach

Scandinavian Journal of Surgery 99: 81 85, 2010 Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach C. T. Wilson, M. A. de Moya Department of Trauma, Emergency Surgery, and Critical Care, Massachusetts General Hospital, Boston, MA, U.S.A. Abstract Background and Aims: The management of gallstone pancreatitis, in particular timing of cholecystectomy, has evolved substantially over the last decade. The trend has been toward earlier cholecystectomy. We review current literature regarding the timing of cholecystectomy in the context of gallstone pancreatitis. Materials and Methods: The authors performed a literature search in PubMed for relevant articles in the English language with greatest weight given to prospective trials compared to observational studies and previous reviews. Results: The literature search yielded 59 articles discussing cholecystectomy in the context of gallstone pancreatitis. Most were retrospective studies or reviews, but there were nine prospective observational studies and two randomized control trials. For mild gallstone pancreatitis, laparoscopic cholecystectomy within 48 hours of presentation (without normalization of pancreatic enzymes or absence of abdominal pain) has been shown to shorten hospital stay without increased morbidity or mortality. Routine preoperative ERCP is unnecessary for patients with mild disease. For more severe disease, timing of cholecystectomy is governed by clinical status. Interval cholecystectomy (>2 weeks after index admission) can be safely done with low risk of recurrence if the patient has had ERCP and sphincterotomy at index admission. Conclusion: Patients with mild gallstone pancreatitis should have cholecystectomy during index admission within 48 hours of arrival, but patients with more severe disease will require cholecystectomy at a later time, depending on the clinical circumstances. Sphincterotomy should be done as soon as possible if cholecystectomy is not feasible early in course. Key words: Gallstone pancreatitis; cholecystectomy; review; standard of care; length of stay; sphincterotomy; patient safety Introduction Acute gallstone pancreatitis is a common condition throughout the world marked by pancreatic inflammation caused by gallstones. While initial treatment Correspondence: Marc de Moya, M.D. 165 Cambridge Street, Suite 810 Boston, MA 02114, U.S.A. Email: mdemoya@partners.org of gallstone pancreatitis is supportive, definitive treatment of gallstone pancreatitis to prevent recurrence requires cholecystectomy to remove the source of gallstones. Without definitive treatment, the recurrence rate of gallstone pancreatitis is as high as 60% (1). ERCP and sphincterotomy can also prevent gallstones from causing recurrent pancreatitis, but will not prevent other complications of cholelithiasis, namely, cholecystitis. Historically, cholecystectomy for gallstone pancreatitis has often been delayed from the index hos-

82 C. T. Wilson, M. A. de Moya pitalization to allow the patient to recover from the physiologic insult of the inciting pancreatitis. However, in the last decade, the standard of care for the timing of cholecystectomy now trends toward earlier intervention. Here, the authors review the most current literature regarding timing of cholecystectomy in the context of gallstone pancreatitis. Materials and methods The authors performed a literature search using PubMed using search terms gallstone, cholelithiasis, pancreatitis, and cholecystectomy. Search results were included in the review if they were in English, and had observational or prospective data regarding the timing of cholecystectomy for gallstone pancreatitis. The greatest weight was given to prospective data, in particular to randomized control trials, but all data was considered. Results PubMed search of the above listed search terms initially yielded 816 results. Review of these results yielded 59 English language articles with data related to timing of cholecystectomy for gallstone pancreatitis. Of these 59 articles, most were based on observational data, but there were nine prospective studies and 2 randomized control trials. Prior to widespread adoption of laparoscopic cholecystectomy there was controversy over the timing of cholecystectomy for gallstone pancreatitis. Historically, the standard of care had been to delay cholecystectomy until at least 2 weeks after onset of gallstone pancreatitis, but in the late 1970 s, this convention was challenged. Several authors published reports of safely doing cholecystectomy for mild gallstone pancreatitis during the index admission (1 4). Even initially, after the laparoscopic cholecystectomy became accepted for elective cholecystectomy, some argued that open cholecystectomy was required if cholecystectomy was to be done within 2 weeks of gallstone pancreatitis due to inflammation. In a 2003 study, elective delayed laparoscopic cholecystectomy had better outcomes than early open cholecystectomy. There was essentially no mortality seen in elective laparoscopic surgery done 15 days after onset of pancreatitis compared to 5% mortality for early open cholecystectomy done within 15 days of onset of symptoms (5). Additionally, when laparoscopic cholecystectomy was used for early intervention after onset of mild gallstone pancreatitis, the procedure was also found to be safe. One of the first studies to document the safety of early laparoscopic cholecystectomy was a 1995 retrospective study showing safety in 122 patients with mild pancreatitis with low rate of conversion and postoperative complications. This same study looked at 20 patients with more severe gallstone pancreatitis, and found an unacceptable rate of complication associated with early laparoscopic cholecystectomy (6). MILD PANCREATITS The largest recent body of literature regarding gallstone pancreatitis and timing of cholecystectomy exists for mild pancreatitis. Mild pancreatitis has multiple definitions, however, many of the studies use the relatively standard definition of pancreatitis with a Ranson score 3 (Fig. 1.) Fig. 1. Treatment algorithm.

Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach 83 Most studies looking at timing of cholecystectomy for mild gallstone pancreatitis, have tried to answer the question of whether it is better to remove the gallbladder during the index hospitalization or delay cholecystectomy for variable amounts of time postdischarge. One of the most important outcomes in these studies is the incidence of recurrent gallstone pancreatitis. The likelihood that recurrent gallstone pancreatitis occurs is thought to increase as the interval between onset of gallstone pancreatitis and cholecystectomy increases. One of the largest observational studies (with more than 8000 patients) to look at this question was one using the nationwide register data in Sweden from 1988 2003. In this study, four groups were compared; Group 1 had cholecystectomy during index stay, Group 2 had cholecystectomy within 30 days of index admission, Group 3 had sphincterotomy within 30 days of index admission, but no cholecystectomy, and Group 4 had neither sphincterotomy nor cholecystectomy. The findings of the studies showed that Group 1 had a slightly longer length of stay compared to Group 2, but had much fewer readmissions for biliary complications. Furthermore, the study found that 31% of patients in Group 3 (who had sphincterotomy within 30 days of index admission) required cholecystectomy within a year of the index admission, presumably for cholecystitis (7). Similar to the study above, most observational data has supported doing laparoscopic cholecystectomy within 2 weeks of the index admission to prevent gallstone pancreatitis recurrence and shorten overall hospital stay (1, 8, 9). One of these studies, done in 2003, showed a 20% rate of recurrence in those patients who were managed with cholecystectomy more than 2 weeks after onset of pancreatitis (8). Although most prospective data is poorly powered, and sparse, there are a handful of small prospective studies that have also confirmed that for mild disease, early cholecystectomy is beneficial compared to delaying surgery beyond 2 weeks (10, 11). One study even showed that the reduction in recurrences made early cholecystectomy cost effective (12). Some studies have even suggested that 2 weeks after index admission is too long to wait with unacceptably high rates of recurrence of gallstone pancreatitis. These authors argue that cholecystectomy should be done during the index admission, and the evidence suggests that this is a safe practice without increased risk of complications related to earlier cholecystectomy (8). One 2008 study, showed that even with a standard of care of targeting cholecystectomy within 2 weeks of index admission, that there was still a 33% rate of biliary related complications including a 13% recurrent pancreatitis rate (13). From there, other studies have argued that even during the index admission the laparoscopic cholecystectomy should take place earlier in the course. In fact, the most scientific prospective studies regarding the timing of cholecystectomy for mild gallstone pancreatitis have been those that have attempted to answer this question. There were two prospective studies done that show a decreased length of stay could be achieved safely by performing laparoscopic cholecystectomy for mild gallstone pancreatitis before serum pancreatic enzymes were normal and before abdominal pain had totally resolved (14,15). These study findings were confirmed by a recent randomized clinical trial comparing laparoscopic cholecystectomy within 48 hours of admission for mild gallstone pancreatitis (Ranson Score 3) to delaying the laparoscopic cholecystectomy until enzymes and abdominal exam was normal. The trial demonstrated a shorter length of stay for the patient who had laparoscopic cholecystectomy within 48 hours regardless of abdominal pain or persistent enzyme abnormalities with no increase in perioperative complication or technical difficulty (16). MODERATE TO SEVERE PANCREATITIS Timing of cholecystectomy in patients with more severe cases of gallstone pancreatitis differs substantially from those with mild disease. These patients often have contraindications to surgery from various physiologic derangements from the inflammatory response of the severe pancreatitis. Review of the literature reveals that there is less controversy over timing of cholecystectomy for these patients. That is because the standard of care for moderate to severe cases of gallstone pancreatitis is to do early ERCP and sphincterotomy which makes the timing of the cholecystectomy more flexible, since presumably these patients are at low risk of recurrent gallstone pancreatitis. The evidence reviewed would support that sphincterotomy during the index admission with interval cholecystectomy is a safe and desirable practice (9, 11, 17 20). Some would suggest that an interval cholecystectomy is not needed after a sphincterotomy. However, patients who have had sphincterotomy are still at risk of developing biliary complications (13). As mentioned above in the Swedish study, 31% of the patients with sphincterotomy within 30 days of the index admission required cholecystectomy within the year, likely from cholecystitis, but possible from recurrent gallstone pancreatitis (7). The risk of gallstone pancreatitis recurrence after sphincterotomy is 0 2% (1, 11). In severe cases of pancreatitis, fluid collections may form (pseudocysts or pancreatic necrosis) and may eventually require operative drainage/management of the fluid collections. Multiple studies have endorsed that it is safest to perform early sphincterotomy in these patients, and delay cholecystectomy until after the fluid collections have resolved, been drained percutaneously, or at the time of operative intervention for collections (18, 21). PREGNANCY One group of patients that a more conservative approach to management of gallstone pancreatitis is often suggested is pregnant patients. While conservative supportive therapy during pregnancy and waiting until delivery to treat patients surgically makes intuitive sense, the evidence would suggest that ERCP and laparoscopic cholecystectomy are well tol-

84 C. T. Wilson, M. A. de Moya erated in pregnant women (22). Furthermore, one 2008 study reported that for patients with gallstone pancreatitis, the fetal mortality rate for conservative vs surgical (laparoscopic cholecystectomy or sphincterotomy group) therapy was 8% versus 2.6% (23). ELDERLY The elderly is another group of patients that a more conservative approach has often been advocated given higher potential complications of surgical treatment. However, like in pregnant patients, laparoscopic cholecystectomy has proven to be well tolerated. Risk of postoperative complications is higher than younger patients have (22 27%), and length of stay is also substantially longer than for younger patients, but the mortality rate is extremely low in the published studies looking at laparoscopic cholecystectomy in patients over the age of 80 (24 25). BILLIARY IMAGING One remaining question related to timing and appropriateness of cholecystectomy for gallstone pancreatitis is what imaging or preoperative work-up should be done to assess for common bile duct stones. Most authors recommend that a patient with choledocholithiasis should proceed to ERCP and sphincterotomy prior to laparoscopic cholecystectomy, and that certainly any evidence of biliary sepsis is a reason to proceed to sphincterotomy expeditiously (1, 18, 26, 27). However, for patients with no evidence of biliary sepsis, who also have mild gallstone pancreatitis, review of the literature shows various approaches to imaging. One approach to imaging the biliary system in patients with mild gallstone pancreatitis is to perform an ERCP on all patients prior to laparoscopic cholecystectomy. This was studied in a randomized control trial comparing routine preoperative ERCP to selective postoperative ERCP for patients with mild gallstone pancreatitis. There was no demonstrable clinical benefit to routine preoperative ERCP, but cost and hospital length of stay increased with this practice (28). While this study shows routine ERCP to be costly and of no benefit, the same researchers investigated the idea of a cheaper more routine preoperative test to determine those patients who might benefit from preoperative ERCP (so called selective preoperative ERCP). They showed that a level of bilirubin greater than 4 mg/dl on hospital day 2 reliably predicted choledocholithiasis, and that using this finding as an indication for ERCP minimized unnecessary procedures (29). Perhaps the most common practice for imaging the biliary system in patients with mild gallstone pancreatitis is to perform an intraoperative cholangiogram at the time of laparoscopic cholecystectomy. Surprisingly however, the studies that have looked at performing routine intraoperative cholangiogram for mild gallstone pancreatitis have shown little benefit (in terms of reducing the incidence of retained common bile duct stones). Two studies have shown that intraoperative cholangiogram does not alter management in the setting of normal preoperative imaging (normal common bile duct on ultrasound) and lab work (serum bilirubin < 1.4 mg/dl) (30, 31). One imaging modality that is promising, but has not yet become common practice, is magnetic resonance cholangiopancreatography (MRCP). At least two studies have shown that MRCP is highly accurate in the preoperative detection of common bile duct stones (32, 33). Of course MRCP has no therapeutic role, so patients who were identified to have common bile duct stones on preoperative imaging still required ERCP and sphincterotomy prior to laparoscopic cholecystectomy. Of note, these studies did not look at hospital cost or length of stay with routine preoperative MRCP. Finally, one group argues that preoperative imaging is entirely not needed for mild gallstone pancreatitis and that all patients should proceed to laparoscopic cholecystectomy expeditiously with intraoperative cholangiogram. This group has excellent experience with laparoscopic common bile duct exploration, and show that if this procedure is available, preoperative ERCP is of no value, and postoperative ERCP is also exceedingly rare (34). Discussion Management of gallstone pancreatitis has evolved substantially as laparoscopic cholecystectomy has become more widespread in its use. Of note the timing of cholecystectomy has become much earlier in the course of the management, especially for patients with mild pancreatitis. For patients with mild gallstone pancreatitis (Ranson score 3), who have no evidence of biliary obstruction (normal serum bilirubin, and normal common bile duct caliber), laparoscopic cholecystectomy within 48 hours of admission is safe and decreases hospital length of stay (even with persistent abdominal pain and elevated serum pancreatic enzymes). Most importantly, this practice makes recurrent gallstone pancreatitis exceedingly unlikely. These patients do not need routine preoperative ERCP, and even intraoperative cholangiogram may be largely unhelpful. MRCP does accurately predict patients who have persistent common bile duct stones, but the value of the additional information given cost and availability of MRCP is questionable. If suspicion of retained common bile duct stones is high enough to warrant MRCP, then ERCP is probably a better choice since sphincterotomy will be possible if retained stones are confirmed on the diagnostic portion of the exam. Patients who would benefit from preoperative ERCP are those with a dilated common bile duct on admission ultrasound or those with an elevated serum bilirubin (> 4 mg/dl) on hospital day 2 of their course. Finally, if the surgeons are comfortable with laparoscopic common bile duct exploration, then preoperative ERCP can be omitted entirely, and reserved for the very minority of patients whose common bile duct stones cannot be cleared by the surgeons at the time of cholecystectomy.

Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach 85 Those patients with relatively strong contraindications to general anesthesia or those with a history of previous abdominal pathology that may make cholecystectomy technically challenging may benefit from sphincterotomy alone (which can be done under light sedation). However, the evidence supports that laparoscopic cholecystectomy is well tolerated even by people with comorbid conditions. Elderly patients and pregnant patients during their second trimester with mild gallstone pancreatitis may benefit from laparoscopic cholecystectomy within 48 hours of admission unless there are other more complicating comorbidities present. For patients with severe gallstone pancreatitis, the timing of cholecystectomy will depend on the clinical course. Patients who are in shock from pancreatitis should not undergo cholecystectomy. 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