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 to- ward earlier cholecystectomy. We review current literature regarding the timing of chole- cystectomy in the context of gallstone pancreatitis. Materials and Methods: The authors performed a literature search in PubMed for rel- evant 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 pre- operative 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 Scandinavian Journal of Surgery 99: 81–85, 2010 Correspondence: Marc de Moya, M.D. 165 Cambridge Street, Suite 810 Boston, MA 02114, U.S.A. Email: [email protected] of gallstone pancreatitis is supportive, definitive treatment of gallstone pancreatitis to prevent recur- rence requires cholecystectomy to remove the source of gallstones. Without definitive treatment, the recur- rence rate of gallstone pancreatitis is as high as 60% (1). ERCP and sphincterotomy can also prevent gall- stones from causing recurrent pancreatitis, but will not prevent other complications of cholelithiasis, namely, cholecystitis. Historically, cholecystectomy for gallstone pan- creatitis has often been delayed from the index hos- INTRODUCTION Acute gallstone pancreatitis is a common condition throughout the world marked by pancreatic inflam- mation caused by gallstones. While initial treatment
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Cholecystectomy for Acute Gallstone Pancreatitis: Early Vs Delayed ApproachC. 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 to- ward earlier cholecystectomy. We review current literature regarding the timing of chole- cystectomy in the context of gallstone pancreatitis.
Materials and Methods: the authors performed a literature search in pubmed for rel- evant 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 pre- operative 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
Scandinavian Journal of Surgery 99: 81–85, 2010
Correspondence: Marc de Moya, M.D. 165 Cambridge Street, Suite 810 Boston, MA 02114, U.S.A. Email: [email protected]
of gallstone pancreatitis is supportive, definitive treatment of gallstone pancreatitis to prevent recur- rence requires cholecystectomy to remove the source of gallstones. Without definitive treatment, the recur- rence rate of gallstone pancreatitis is as high as 60% (1). ERCP and sphincterotomy can also prevent gall- stones from causing recurrent pancreatitis, but will not prevent other complications of cholelithiasis, namely, cholecystitis.
Historically, cholecystectomy for gallstone pan- creatitis has often been delayed from the index hos-
InTRoDUCTIon
Acute gallstone pancreatitis is a common condition throughout the world marked by pancreatic inflam- mation caused by gallstones. While initial treatment
82 C. T. Wilson, M. A. de Moya
pitalization to allow the patient to recover from the physiologic insult of the inciting pancreatitis. How- ever, in the last decade, the standard of care for the timing of cholecystectomy now trends toward earlier intervention. Here, the authors review the most cur- rent 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”, “pancrea- titis”, and “cholecystectomy”. Search results were included in the review if they were in English, and had observa- tional or prospective data regarding the timing of cholecys- tectomy for gallstone pancreatitis. The greatest weight was given to prospective data, in particular to randomized con- trol trials, but all data was considered.
RESUlTS
PubMed search of the above listed search terms ini- tially yielded 816 results. Review of these results yielded 59 English language articles with data related to timing of cholecystectomy for gallstone pancreati- tis. of these 59 articles, most were based on observa- tional data, but there were nine prospective studies and 2 randomized control trials.
Prior to widespread adoption of laparoscopic cholecystectomy there was controversy over the tim- ing of cholecystectomy for gallstone pancreatitis. His- torically, the standard of care had been to delay chole- cystectomy until at least 2 weeks after onset of gall- stone pancreatitis, but in the late 1970’s, this conven-
tion was challenged. Several authors published re- ports of safely doing cholecystectomy for mild gall- stone pancreatitis during the index admission (1–4).
Even initially, after the laparoscopic cholecystec- tomy 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 pan- creatitis 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 pa- tients with mild pancreatitis with low rate of conver- sion and postoperative complications. This same study looked at 20 patients with more severe gall- stone pancreatitis, and found an unacceptable rate of complication associated with early laparoscopic cholecystectomy (6).
MIlD PAnCREATITS
The largest recent body of literature regarding gall- stone pancreatitis and timing of cholecystectomy ex- ists for mild pancreatitis. Mild pancreatitis has mul- tiple definitions, however, many of the studies use the relatively standard definition of pancreatitis with a Ranson score ≤ 3 (Fig. 1.)
Fig. 1. Treatment algorithm.
83Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach
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 post- discharge. 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 inter- val between onset of gallstone pancreatitis and chole- cystectomy 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 sphinctero- tomy within 30 days of index admission, but no cholecystectomy, and Group 4 had neither sphinc- terotomy 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. Fur- thermore, 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 chole- cystitis (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 pa- tients 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 chole- cystectomy is beneficial compared to delaying sur- gery beyond 2 weeks (10, 11). one study even showed that the reduction in recurrences made early chole- cystectomy cost effective (12).
Some studies have even suggested that 2 weeks after index admission is too long to wait with unac- ceptably high rates of recurrence of gallstone pan- creatitis. 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 cholecystec- tomy 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 chole- cystectomy should take place earlier in the course. In fact, the most scientific prospective studies regarding the timing of cholecystectomy for mild gallstone pan- creatitis 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 be- fore serum pancreatic enzymes were normal and be- fore abdominal pain had totally resolved (14,15). These study findings were confirmed by a recent ran- domized clinical trial comparing laparoscopic chole- cystectomy 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 lap- aroscopic cholecystectomy within 48 hours regardless of abdominal pain or persistent enzyme abnormali- ties with no increase in perioperative complication or technical difficulty (16).
MoDERATE To SEVERE PAnCREATITIS
Timing of cholecystectomy in patients with more se- vere cases of gallstone pancreatitis differs substan- tially from those with mild disease. These patients often have contraindications to surgery from various physiologic derangements from the inflammatory re- sponse of the severe pancreatitis. Review of the lit- erature reveals that there is less controversy over tim- ing 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 chole- cystectomy more flexible, since presumably these pa- tients are at low risk of recurrent gallstone pancreati- tis. The evidence reviewed would support that sphincterotomy during the index admission with in- terval cholecystectomy is a safe and desirable practice (9, 11, 17–20).
Some would suggest that an interval cholecystec- tomy is not needed after a sphincterotomy. However, patients who have had sphincterotomy are still at risk of developing biliary complications (13). As men- tioned above in the Swedish study, 31% of the pa- tients with sphincterotomy within 30 days of the in- dex admission required cholecystectomy within the year, likely from cholecystitis, but possible from re- current gallstone pancreatitis (7). The risk of gall- stone 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 en- dorsed that it is safest to perform early sphinctero- tomy 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 ap- proach to management of gallstone pancreatitis is often suggested is pregnant patients. While conserva- tive supportive therapy during pregnancy and wait- ing 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 sphinc- terotomy 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 treat- ment. However, like in pregnant patients, laparo- scopic cholecystectomy has proven to be well toler- ated. Risk of postoperative complications is higher than younger patients have (22–27%), and length of stay is also substantially longer than for younger pa- tients, but the mortality rate is extremely low in the published studies looking at laparoscopic cholecys- tectomy in patients over the age of 80 (24–25).
BIllIARY IMAGInG
one remaining question related to timing and ap- propriateness of cholecystectomy for gallstone pan- creatitis is what imaging or preoperative work-up should be done to assess for common bile duct stones. Most authors recommend that a patient with chole- docholithiasis should proceed to ERCP and sphinc- terotomy prior to laparoscopic cholecystectomy, and that certainly any evidence of biliary sepsis is a rea- son to proceed to sphincterotomy expeditiously (1, 18, 26, 27). However, for patients with no evidence of biliary sepsis, who also have mild gallstone pan- creatitis, review of the literature shows various ap- proaches to imaging.
one approach to imaging the biliary system in pa- tients with mild gallstone pancreatitis is to perform an ERCP on all patients prior to laparoscopic chole- cystectomy. This was studied in a randomized control trial comparing routine preoperative ERCP to selec- tive postoperative ERCP for patients with mild gall- stone pancreatitis. There was no demonstrable clini- cal 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 inves- tigated the idea of a cheaper more routine preopera- tive test to determine those patients who might ben- efit from preoperative ERCP (so called selective pre- operative ERCP). They showed that a level of biliru- bin greater than 4 mg/dl on hospital day 2 reliably predicted choledocholithiasis, and that using this finding as an indication for ERCP minimized unnec- essary procedures (29).
Perhaps the most common practice for imaging the biliary system in patients with mild gallstone pan- creatitis is to perform an intraoperative cholangio- gram 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 com- mon bile duct stones). Two studies have shown that intraoperative cholangiogram does not alter manage-
ment 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 reso- nance cholangiopancreatography (MRCP). At least two studies have shown that MRCP is highly accu- rate in the preoperative detection of common bile duct stones (32, 33). of course MRCP has no thera- peutic role, so patients who were identified to have common bile duct stones on preoperative imaging still required ERCP and sphincterotomy prior to lap- aroscopic 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 imag- ing is entirely not needed for mild gallstone pancrea- titis and that all patients should proceed to laparo- scopic cholecystectomy expeditiously with intraop- erative cholangiogram. This group has excellent ex- perience with laparoscopic common bile duct explo- ration, 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 tim- ing of cholecystectomy has become much earlier in the course of the management, especially for patients with mild pancreatitis.
For patients with mild gallstone pancreatitis (Ran- son score ≤ 3), who have no evidence of biliary ob- struction (normal serum bilirubin, and normal com- mon bile duct caliber), laparoscopic cholecystectomy within 48 hours of admission is safe and decreases hospital length of stay (even with persistent abdomi- nal pain and elevated serum pancreatic enzymes). Most importantly, this practice makes recurrent gall- stone pancreatitis exceedingly unlikely. These pa- tients 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 se- rum bilirubin (> 4 mg/dl) on hospital day 2 of their course. Finally, if the surgeons are comfortable with laparoscopic common bile duct exploration, then pre- operative 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.
85Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach
Those patients with relatively strong contraindica- tions to general anesthesia or those with a history of previous abdominal pathology that may make chole- cystectomy technically challenging may benefit from sphincterotomy alone (which can be done under light sedation). However, the evidence supports that lap- aroscopic 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 ad- mission unless there are other more complicating co- morbidities 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. Alternatively, these patients can have urgent sphincterotomy, and an interval cholecystectomy can be done weeks or even months later after they have recovered from their severe pancreatitis. The timing of cholecystec- tomy can also coincide with procedures for internal drainage of pseudocyst or debridement of necrotizing pancreatitis.
The most challenging patients will remain those who have moderate gallstone pancreatitis. For this group of patients, factors, such as age, comorbid con- ditions, social circumstances, and patient preference will guide timing of cholecystectomy, but ultimately as with all clinical decisions, it will be up to the judg- ment of the treating clinician to determine what is the appropriate timing for cholecystectomy.
REFEREnCES
01. lee JK, Ryu JK, Park JK et al: Roles of endoscopic sphinctero- tomy and cholecystectomy in acute biliary pancreatitis. He- patogastroenterol 2008;55(88):1981–1985
02. Elfstrom J: The timing of cholecystectomy in patients with gallstone pancreatitis: a retrospective analysis of 89 patients. Acta Chir Scand 1978;144:487–490
03. Ranson JH: The timing of biliary surgery in acute pancreatitis. Ann Surg 1979;189:654–663
04. Kelly TR: Gallstone pancreatitis: the timing of surgery. Surgery. 1980;88:345–350
05. Bedirli A, Sözüer EM, Sakrak o, Babayi git H, Yilmaz Z. Com- parison of the results of early, delayed and elective surgery in biliary pancreatitis. Turk J Gastroenterol. 2003;14(2):97–101
06. Tang E, Stain, SC, Tang G, et al: Timing of laparoscopic surgery in gallstone pancreatitis. Arch Surg 1995;130(5):496–500
07. Sandzén B, Haapamäki MM, nilsson E, Stenlund HC, oman M: Cholecystectomy and sphincterotomy in patients with mild acute biliary pancreatitis in Sweden 1988–2003: a nationwide register study. BMC Gastroenterol. 2009;9:80
08. McCullough l, Sutherland F, Preshaw R, Kim S: Gallstone pancreatitis: does discharge and readmission for cholecystec- tomy affect outcome? HPB (oxford) 2003;5(2):96–99
09. Uhl W, Müller CA, Krähenbühl l et al: Acute gallstone pan- creatitis: timing of laparoscopic cholecystectomy in mild and severe disease. Surg Endosc 1999;13(11):1070–1076
10. Clarke T, Sohn H, Kelso R et al: Planned early discharge-elec- tive surgical readmission pathway for patients with gallstone pancreatitis. Arch Surg 2008;143(9):901–905
11. Hernandez V, Pascual I, Almela P et al: Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy or endoscopic sphincterotomy. Am J Gastroenterol 2004;99(12): 2417–2423
12. Monkhouse SJ, Court El, Dash I, Coombs nJ: Two-week target for laparoscopic cholecystectomy following gallstone pancrea-
titis is achievable and cost neutral. Br J Surg 2009;96(7):751– 755
13. Ito K, Ito H, Whang EE: Timing of cholecystectomy for biliary pancreatitis: do the data support current guidelines? J Gastro- intest Surg 2008;12(12):2164–2170…
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 to- ward earlier cholecystectomy. We review current literature regarding the timing of chole- cystectomy in the context of gallstone pancreatitis.
Materials and Methods: the authors performed a literature search in pubmed for rel- evant 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 pre- operative 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
Scandinavian Journal of Surgery 99: 81–85, 2010
Correspondence: Marc de Moya, M.D. 165 Cambridge Street, Suite 810 Boston, MA 02114, U.S.A. Email: [email protected]
of gallstone pancreatitis is supportive, definitive treatment of gallstone pancreatitis to prevent recur- rence requires cholecystectomy to remove the source of gallstones. Without definitive treatment, the recur- rence rate of gallstone pancreatitis is as high as 60% (1). ERCP and sphincterotomy can also prevent gall- stones from causing recurrent pancreatitis, but will not prevent other complications of cholelithiasis, namely, cholecystitis.
Historically, cholecystectomy for gallstone pan- creatitis has often been delayed from the index hos-
InTRoDUCTIon
Acute gallstone pancreatitis is a common condition throughout the world marked by pancreatic inflam- mation caused by gallstones. While initial treatment
82 C. T. Wilson, M. A. de Moya
pitalization to allow the patient to recover from the physiologic insult of the inciting pancreatitis. How- ever, in the last decade, the standard of care for the timing of cholecystectomy now trends toward earlier intervention. Here, the authors review the most cur- rent 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”, “pancrea- titis”, and “cholecystectomy”. Search results were included in the review if they were in English, and had observa- tional or prospective data regarding the timing of cholecys- tectomy for gallstone pancreatitis. The greatest weight was given to prospective data, in particular to randomized con- trol trials, but all data was considered.
RESUlTS
PubMed search of the above listed search terms ini- tially yielded 816 results. Review of these results yielded 59 English language articles with data related to timing of cholecystectomy for gallstone pancreati- tis. of these 59 articles, most were based on observa- tional data, but there were nine prospective studies and 2 randomized control trials.
Prior to widespread adoption of laparoscopic cholecystectomy there was controversy over the tim- ing of cholecystectomy for gallstone pancreatitis. His- torically, the standard of care had been to delay chole- cystectomy until at least 2 weeks after onset of gall- stone pancreatitis, but in the late 1970’s, this conven-
tion was challenged. Several authors published re- ports of safely doing cholecystectomy for mild gall- stone pancreatitis during the index admission (1–4).
Even initially, after the laparoscopic cholecystec- tomy 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 pan- creatitis 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 pa- tients with mild pancreatitis with low rate of conver- sion and postoperative complications. This same study looked at 20 patients with more severe gall- stone pancreatitis, and found an unacceptable rate of complication associated with early laparoscopic cholecystectomy (6).
MIlD PAnCREATITS
The largest recent body of literature regarding gall- stone pancreatitis and timing of cholecystectomy ex- ists for mild pancreatitis. Mild pancreatitis has mul- tiple definitions, however, many of the studies use the relatively standard definition of pancreatitis with a Ranson score ≤ 3 (Fig. 1.)
Fig. 1. Treatment algorithm.
83Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach
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 post- discharge. 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 inter- val between onset of gallstone pancreatitis and chole- cystectomy 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 sphinctero- tomy within 30 days of index admission, but no cholecystectomy, and Group 4 had neither sphinc- terotomy 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. Fur- thermore, 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 chole- cystitis (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 pa- tients 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 chole- cystectomy is beneficial compared to delaying sur- gery beyond 2 weeks (10, 11). one study even showed that the reduction in recurrences made early chole- cystectomy cost effective (12).
Some studies have even suggested that 2 weeks after index admission is too long to wait with unac- ceptably high rates of recurrence of gallstone pan- creatitis. 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 cholecystec- tomy 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 chole- cystectomy should take place earlier in the course. In fact, the most scientific prospective studies regarding the timing of cholecystectomy for mild gallstone pan- creatitis 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 be- fore serum pancreatic enzymes were normal and be- fore abdominal pain had totally resolved (14,15). These study findings were confirmed by a recent ran- domized clinical trial comparing laparoscopic chole- cystectomy 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 lap- aroscopic cholecystectomy within 48 hours regardless of abdominal pain or persistent enzyme abnormali- ties with no increase in perioperative complication or technical difficulty (16).
MoDERATE To SEVERE PAnCREATITIS
Timing of cholecystectomy in patients with more se- vere cases of gallstone pancreatitis differs substan- tially from those with mild disease. These patients often have contraindications to surgery from various physiologic derangements from the inflammatory re- sponse of the severe pancreatitis. Review of the lit- erature reveals that there is less controversy over tim- ing 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 chole- cystectomy more flexible, since presumably these pa- tients are at low risk of recurrent gallstone pancreati- tis. The evidence reviewed would support that sphincterotomy during the index admission with in- terval cholecystectomy is a safe and desirable practice (9, 11, 17–20).
Some would suggest that an interval cholecystec- tomy is not needed after a sphincterotomy. However, patients who have had sphincterotomy are still at risk of developing biliary complications (13). As men- tioned above in the Swedish study, 31% of the pa- tients with sphincterotomy within 30 days of the in- dex admission required cholecystectomy within the year, likely from cholecystitis, but possible from re- current gallstone pancreatitis (7). The risk of gall- stone 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 en- dorsed that it is safest to perform early sphinctero- tomy 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 ap- proach to management of gallstone pancreatitis is often suggested is pregnant patients. While conserva- tive supportive therapy during pregnancy and wait- ing 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 sphinc- terotomy 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 treat- ment. However, like in pregnant patients, laparo- scopic cholecystectomy has proven to be well toler- ated. Risk of postoperative complications is higher than younger patients have (22–27%), and length of stay is also substantially longer than for younger pa- tients, but the mortality rate is extremely low in the published studies looking at laparoscopic cholecys- tectomy in patients over the age of 80 (24–25).
BIllIARY IMAGInG
one remaining question related to timing and ap- propriateness of cholecystectomy for gallstone pan- creatitis is what imaging or preoperative work-up should be done to assess for common bile duct stones. Most authors recommend that a patient with chole- docholithiasis should proceed to ERCP and sphinc- terotomy prior to laparoscopic cholecystectomy, and that certainly any evidence of biliary sepsis is a rea- son to proceed to sphincterotomy expeditiously (1, 18, 26, 27). However, for patients with no evidence of biliary sepsis, who also have mild gallstone pan- creatitis, review of the literature shows various ap- proaches to imaging.
one approach to imaging the biliary system in pa- tients with mild gallstone pancreatitis is to perform an ERCP on all patients prior to laparoscopic chole- cystectomy. This was studied in a randomized control trial comparing routine preoperative ERCP to selec- tive postoperative ERCP for patients with mild gall- stone pancreatitis. There was no demonstrable clini- cal 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 inves- tigated the idea of a cheaper more routine preopera- tive test to determine those patients who might ben- efit from preoperative ERCP (so called selective pre- operative ERCP). They showed that a level of biliru- bin greater than 4 mg/dl on hospital day 2 reliably predicted choledocholithiasis, and that using this finding as an indication for ERCP minimized unnec- essary procedures (29).
Perhaps the most common practice for imaging the biliary system in patients with mild gallstone pan- creatitis is to perform an intraoperative cholangio- gram 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 com- mon bile duct stones). Two studies have shown that intraoperative cholangiogram does not alter manage-
ment 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 reso- nance cholangiopancreatography (MRCP). At least two studies have shown that MRCP is highly accu- rate in the preoperative detection of common bile duct stones (32, 33). of course MRCP has no thera- peutic role, so patients who were identified to have common bile duct stones on preoperative imaging still required ERCP and sphincterotomy prior to lap- aroscopic 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 imag- ing is entirely not needed for mild gallstone pancrea- titis and that all patients should proceed to laparo- scopic cholecystectomy expeditiously with intraop- erative cholangiogram. This group has excellent ex- perience with laparoscopic common bile duct explo- ration, 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 tim- ing of cholecystectomy has become much earlier in the course of the management, especially for patients with mild pancreatitis.
For patients with mild gallstone pancreatitis (Ran- son score ≤ 3), who have no evidence of biliary ob- struction (normal serum bilirubin, and normal com- mon bile duct caliber), laparoscopic cholecystectomy within 48 hours of admission is safe and decreases hospital length of stay (even with persistent abdomi- nal pain and elevated serum pancreatic enzymes). Most importantly, this practice makes recurrent gall- stone pancreatitis exceedingly unlikely. These pa- tients 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 se- rum bilirubin (> 4 mg/dl) on hospital day 2 of their course. Finally, if the surgeons are comfortable with laparoscopic common bile duct exploration, then pre- operative 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.
85Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach
Those patients with relatively strong contraindica- tions to general anesthesia or those with a history of previous abdominal pathology that may make chole- cystectomy technically challenging may benefit from sphincterotomy alone (which can be done under light sedation). However, the evidence supports that lap- aroscopic 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 ad- mission unless there are other more complicating co- morbidities 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. Alternatively, these patients can have urgent sphincterotomy, and an interval cholecystectomy can be done weeks or even months later after they have recovered from their severe pancreatitis. The timing of cholecystec- tomy can also coincide with procedures for internal drainage of pseudocyst or debridement of necrotizing pancreatitis.
The most challenging patients will remain those who have moderate gallstone pancreatitis. For this group of patients, factors, such as age, comorbid con- ditions, social circumstances, and patient preference will guide timing of cholecystectomy, but ultimately as with all clinical decisions, it will be up to the judg- ment of the treating clinician to determine what is the appropriate timing for cholecystectomy.
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