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The management of gallstone pancreatitis in the era of laparoscopic cholecystectomy
The Management of Gallstone Pancreatitis the Era of Laparoscopic Cholecystectomy Thomas
R. Kelly, MD, Dsc, FACS,*
Akron,
W
hen we wrote an editorial opinion 5 years ago on the proper timing of surgery in gallstone pancreatitis, we never dreamed how much the advent of laparoscopic cholecystectomy in 1989 would change current management. For the traditional open cholecystectomy and cholangiogram we recommended a delay of at least 3 days in the more severe cases to allow acute symptoms to subside, but operation before hospital charge.’ Now immediate endoscopic retrograde cholangiopancreatography (ERCP) is being widely urged to abort the acute attack. It is also being performed with increasing frequency because laparoscopic cholecystectomy is planned. The indications for urgent ERCP are very limited in gallstone pancreatitis. In the retrospective reviews of experience with this procedure, including sphincterotomy and stone extraction if needed, the benefits are uncertain and the complication rate is the expected 3-4%. Two comprehensive, prospective, and randomized studies of early ERCP have been published. In both studies the cases were stratified into mild and severe groups. Both included sphincteroplasty and stone extraction whenever stones were encountered. In both studies early ERCP did not alter the course of mild pancreatitis. In severe pancreatitis, Fan and colleagues found fewer bouts of septic cholangitis (0% vs 12%) when ERCP was performed within the first 24 hours. This was the only statistically significant benefit. This study was conducted in Hong Kong, where many patients have large soft primary stones in the common duct, so that these results may not be applicable to a non-Asian population. Neoptolemos and colleagues conducted their studies in England, where ERCP within 72 hours reduced complications significantly ( 18% of 22 cases having ERCP, vs 54% of 24 cases treated conventionally), but only in the severe cases.“’ These are relatively small numbers, so that more time and cases are needed. These results differ from the results in a randomized study of timing for open cholecystectomy. In both severe and mild cases the removal of an impacted ampullary stone did not ameliorate the progression of the pancreatitis.4
Am J Surg. 1996;172:225-227 From the Department of Surgery, Northeastern Ohio Universities, College of Medicine, Akron City Hospital, Akron USA; and the Department of Surgery, Wright State University School of Medicine, Dayton, Ohio. Requests for reprints should be addressed to Dan W. Elliott, MD, Department of Surgery, Wright State University, Miami Valley Hospital, 7th Floor, CHE Building, 1 Wyoming Street, Dayton, Ohio 45409. Manuscript submitted August 15, 1995 and accepted September 14, 1995. * Dr. Kelly died April 23, 1996.
0 1996 by Excerpta All rights reserved.
Medica,
Inc.
in
Ohio, Dan W. Elliott, MD, FACS, Dayton, Ohio
The endoscopist may advise that early ERCP to remove stones is necessary to keep from “blowing the chance” to abort the pancreatitis, but this is wrong. Septic cholangitis, not gallstone pancreatitis, is the one indication for immediate ERCP. As Fan and colleagues have shown, patients with septic cholangitis occasionally have an elevated amylase and must be suspected of having pancreatitis as well. In these patients an impacted ampullary stone was regularly found at ERCP and removed with benefit.* If such a stone cannot be removed the manipulation and injections of dye will make the sepsis worse and prompt open operation is needed. The combination of cholangitis and pancreatitis is uncommon, probably because the pathophysiology of the two diseases are different. With cholangitis the stone is larger, usually blocks the entire ampulla of Vater, and remains impacted until removed. In gallstone pancreatitis it is reasonable to assume the stones are smaller, and impact only briefly if at all, because most of them pass spontaneously into the duodenum and can be strained from the stools. The percent of patients found to harbor residual stones in the common duct declines steadily each day that passes hetween onset and operation. This also suggests that these stones are passing spontaneously as the attack subsides, but no one can be sure that all have passed. Therefore a cholangiogram is always needed when the gallbladder is removed. Any stones still rattling around in the common bile duct are not the stones that caused this attack. They are the followers that will cause the subsequent bouts if not removed. A small number of patients with severe attacks develop pancreatic necrosis and require later debridement, lavage, and drainage of infected necrotic tissue. This was not altered by early open operation to remove the stones left behind in the common duct. Autopsied patients who died of gallstone pancreatitis commonly had a necrotic pancreas without an impacted ampullary stone.4 Presumably the stone passed early in the course of the disease but the damage to the pancreas had been done. Most of the little we know about the cause of gallstone pancreatitis comes from animal studies. These show that the primary determinant of the severity of pancreatic inflammation is the initial exocrine leak into the parenchyma of the gland. The fact that early stone removal by operation does not alter the course of pancreatitis lends support to this concept. Whether or not early ERCP can reduce pancreatic necrosis as Neoptolemos believes’ remains to be seen. For the present, early or immediate ERCP should be limited to the severe cases, those with septic cholangitis, and those not improving as expected. At laparoscopic cholecystectomy a cholangiogram should regularly be performed to determine whether any stones re0002-961 O/96/$1 PII SOOO2-9610(96)00104-3
5.00
225
main. This will be negative most of the time when operation has been delayed to allow recovery from the acute symptoms. However, if stones are present these can usually be removed by laparoscopic techniques, which are improving and still evolving.6 If unsuccessful, postoperative ERCP and sphincterotomy or open choledochotomy is indicated. Emergency or preoperative ERCP should become infrequent, and postoperative ERCP performed only when needed for known therapeutic reasons. In the overwhelming majority of cases the necessary definitive surgery can be performed by the same surgeon at the same time in the same setting. In the future, laparoscopic cholecystectomy combined with laparoscopic cholangiography and bile duct clearance will probably become as commonplace as open cholecystectomy and common bile duct exploration has been in the past.’
REFERENCES 1. Kelly TR, Elliott DW. Proper timing of surgery for gallstone pancreatitis. AmJ Surg. 1990;159:361-362. 2. Fan TS, Lai ECS, Mok FPT, et al. Early treatment of acute biliary pancreatitis by endoscopic papillotomy. NEJM. 1993;328:228-232. 3. Neoptolemos JP, Carr-Locke DL, London NJ, et al. Controlled trial of urgen endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lmcet. 1988;29:979-983. 4. Kelly TR, Wagner DS. Gallstone pancreatitis: a prospective randomized trial of the timing of surgery. Surgery. 1988;104:600-605. 5. Neoptolemos JP. Endoscopic sphinceterotomy in acute gallstone pancreatitis. Br J Surg. 1993;80:547-549. 6. Roush TS, Traverso LW. Management and long-term follow-up of patients with positive cholangiograms during laparoscopic cholecystectomy. Am J Lug. 1995;169:484-487. 7. Soper NJ, Brunt M, Gallery Ml’, et al. Role of laparoscopic cholecystectomy in the management of gallstone pancreatitis. Am J Surg. 1994;167:42-51.
EDITORIAL
COMMENT
The patient presenting with gallstone pancreatitis has traditionally been treated with open cholecystectomy and cholangiogram following resolution of the acute pancreatitis, but usually during the same hospitalization. Presently, the patient may be treated with preoperative ERCP and removal of stones, intraoperatively with laparoscopic or open common bile duct exploration, or postoperatively with ERCP and stone removal for those identified as having common duct stones during laparoscopic cholecystectomy. There are even those who recommend leaving stones identified at laparoscopic cholangiography in place for spontaneous passage, if they are small. Preoperative ERCP for gallstone pancreatitis is of unclear value in patients with mild or resolving pancreatitis, but this is not the case for severe and/or worsening gallstone pancreatitis. There are prospective randomized data from controlled clinical trials that demonstrate markedly reduced mortality if preoperative urgent ERCP is performed in this select group of patients. Neoptolemos et al, in the United Kingdom, studied 121 patients with urgent ERCP being performed in 59 patients within 72 hours in one group treated with urgent ERCP compared with 62 patients in another group treated conservatively with observation and subsequent cholecystectomy. There were fewer complications and a lower mortality among patients treated with urgent ERCP. This was partic226
THE AMERICAN
JOURNAL
OF
SURGERY”
VOLUME
172
ularly notable among those in whom the pancreatitis was severe. Among the 53 patients with severe pancreatitis, 6 of 25 treated with urgent ERCP had complications with 1 death (24% morbidity and 1.7% mortality), while those undergoing conventional treatment had complications in 17 of 28 with 5 deaths (61% morbidity and 17.9% mortality). Hospital stay was significantly shortened in the ERCP group (median, 9.5 vs 17 days).’ A second prospective randomized trial from San Diego demonstrated similar results in 70 consecutive patients. In this paper, no complications were attributal to ERCP or endoscopic sphincterotomy, and the 2 deaths in the series occurred in patients who had undergone conventional treatment without ERCP.’ In the subset of patients who present with both acute pancreatitis and cholangitis, there is again definite evidence that early ERCP may reduce morbidity and mortality. Among patients with urgent preoperative ERCP, the mortality rate was 4%, while it was 33% among those treated without ERCP.’ Fan et al also report a benefit of obtaining early ERCP in the course of severe acute gallstone pancreatitis agam with benefit limited to certain subsets of the patients.4 Another study that would suggest that ERCP might be useful in reducing mortality and severe gallstone pancreatitis comes from autopsy data. Carter reported a postmortem series of 132 cases of fatal acute pancreatitis. One-third of these cases were first diagnosed as being of gallstone etiology at the time of the postmortem.5 Earlier identification of the gallstone etiology may have allowed intervention and improved outcome in severe pancreatitis. It is sometimes difficult to identify the biliary origin of pancreatitis with noncholangiographic studies. In a series of 50 patients assessed with respect to biliary origin of pancreatitis, CT and ultrasound could not reliably make the diagnosis of biliary origin of the pancreatitis.6 Lux et al also demonstrated the relative inability of standard laboratory tests and ultrasound to differentiate biliary and alcoholic pancreatitis7 In this study of 44 patients, half with biliary and half with alcoholic origin of the disease, laboratory tests were not useful in discriminating alcoholic vs gallstone pancreatitis patients, and ultrasound was found to have a 68% sensitivity. Given the fact that ERCP can be used for immediate therapeutic intervention, with improved outcome, it is clearly a useful test for those with severe and/or worsening pancreatitis suspected to be of gallstone etiology. In summary, while a variety of approaches may be successful for mild or improving pancreatitis, those with severe and/or worsening pancreatitis, especially those suspected to be of gallstone etiology, should probably undergo urgent ERCP. Given the inability of ultrasound and laboratory determinants to entirely differentiate gallstone and alcoholic pancreatitis, it may be wise to extend this indication to all patients with severe and/or worsening pancreatitis. In patients with a mild or resolving pancreatitis, it is currently our approach to avoid preoperative ERCP and proceed directly with laparoscopic cholecystectomy and cholangiog raphy. Management of identified stones would depend on local expertise, but either laparoscopic common duct stone removal or postoperative ERCP with stone removal are acceptable alternatives. I do not personally feel that it is wise to leave identified stones for postoperative spontaneous pasSEPTEMBER
1996
1 MANAGEMENT
sage. In our new era of laparoscopic surgery, this is clearly an evolving field and further extensive prospective studies will be necessary to entirelv delineate the best management for these Datients. It is cldar that the last chapter Las not been written in the management of common bile duct stones and gallstone pancreatitis. Gary C. Vitale, MD Department of Surgery University of Louisville Louisville, Kentucky
REFERENCES 1. Pitt HA, Gomes AS, Lois JF, Mann LL, Deutsch LS, Longmire WP, Jr. Does preoperative hiliary drainage reduce operative risk or increase hospital cost? Ann Sq. 1985;201:545-553.
THE
AMERICAN
OF
GALLSTONE
PANCREATITIS/KELLY
AND
ELLIOT
2. Seyrig JA, Liguory C, Medun B, Ink 0, Buffet C. Endoscopy in tumors of the Oddi region. Diagnostic and therapeutic possibilities. Gastroenterol Clin Bd 1985;9:103-108. 3. Huibregtse K, Schneider B, Rauws E, Tyrgat GN. Carcmoma of the ampulla of Vater. The role of endoscoplc drainage. Slnrg Endosc. 1987;1:79-52. 4. Fan ST, Lai ECS, Mok FPT, et al. Early treatment of acute biliary pancreatitis by endoscoplc pap&>tomy. NE/M. 1991;328:228-232. 5. Nakao NL, Siegal JH, Stenger R], Gelh AM. Tumours of the ampulla of Vater: early diagnosis by intra-ampullary biopsy during endoscopx cannulatlon. Two case presentations and a rewew of the literature. Gastroenterolqy. 1982;83:459-464. 6. Safrany L. Duodenoscopy and hiopsy: irxernational workshop. In: Classen M, Geenen J, Kawai K, eds. T/w Papila of Vater ad Its Diseases. Baden-Baden: Witzstrock, 197966-T 1. 7. Bourgeois N, Dunham F, Verhest A, Cremer M. Endoscopic biopsies of the papilla of Vater at the time of endoscopic sphincterotomy: difficulties m interpretation. Gastrointest Edosc. 1984;30:163-166.
JOURNAL
OF SURGERY@
VOLUME
172
SEPTEMBER
1996
227
R. Kelly, MD, Dsc, FACS,*
Akron,
W
hen we wrote an editorial opinion 5 years ago on the proper timing of surgery in gallstone pancreatitis, we never dreamed how much the advent of laparoscopic cholecystectomy in 1989 would change current management. For the traditional open cholecystectomy and cholangiogram we recommended a delay of at least 3 days in the more severe cases to allow acute symptoms to subside, but operation before hospital charge.’ Now immediate endoscopic retrograde cholangiopancreatography (ERCP) is being widely urged to abort the acute attack. It is also being performed with increasing frequency because laparoscopic cholecystectomy is planned. The indications for urgent ERCP are very limited in gallstone pancreatitis. In the retrospective reviews of experience with this procedure, including sphincterotomy and stone extraction if needed, the benefits are uncertain and the complication rate is the expected 3-4%. Two comprehensive, prospective, and randomized studies of early ERCP have been published. In both studies the cases were stratified into mild and severe groups. Both included sphincteroplasty and stone extraction whenever stones were encountered. In both studies early ERCP did not alter the course of mild pancreatitis. In severe pancreatitis, Fan and colleagues found fewer bouts of septic cholangitis (0% vs 12%) when ERCP was performed within the first 24 hours. This was the only statistically significant benefit. This study was conducted in Hong Kong, where many patients have large soft primary stones in the common duct, so that these results may not be applicable to a non-Asian population. Neoptolemos and colleagues conducted their studies in England, where ERCP within 72 hours reduced complications significantly ( 18% of 22 cases having ERCP, vs 54% of 24 cases treated conventionally), but only in the severe cases.“’ These are relatively small numbers, so that more time and cases are needed. These results differ from the results in a randomized study of timing for open cholecystectomy. In both severe and mild cases the removal of an impacted ampullary stone did not ameliorate the progression of the pancreatitis.4
Am J Surg. 1996;172:225-227 From the Department of Surgery, Northeastern Ohio Universities, College of Medicine, Akron City Hospital, Akron USA; and the Department of Surgery, Wright State University School of Medicine, Dayton, Ohio. Requests for reprints should be addressed to Dan W. Elliott, MD, Department of Surgery, Wright State University, Miami Valley Hospital, 7th Floor, CHE Building, 1 Wyoming Street, Dayton, Ohio 45409. Manuscript submitted August 15, 1995 and accepted September 14, 1995. * Dr. Kelly died April 23, 1996.
0 1996 by Excerpta All rights reserved.
Medica,
Inc.
in
Ohio, Dan W. Elliott, MD, FACS, Dayton, Ohio
The endoscopist may advise that early ERCP to remove stones is necessary to keep from “blowing the chance” to abort the pancreatitis, but this is wrong. Septic cholangitis, not gallstone pancreatitis, is the one indication for immediate ERCP. As Fan and colleagues have shown, patients with septic cholangitis occasionally have an elevated amylase and must be suspected of having pancreatitis as well. In these patients an impacted ampullary stone was regularly found at ERCP and removed with benefit.* If such a stone cannot be removed the manipulation and injections of dye will make the sepsis worse and prompt open operation is needed. The combination of cholangitis and pancreatitis is uncommon, probably because the pathophysiology of the two diseases are different. With cholangitis the stone is larger, usually blocks the entire ampulla of Vater, and remains impacted until removed. In gallstone pancreatitis it is reasonable to assume the stones are smaller, and impact only briefly if at all, because most of them pass spontaneously into the duodenum and can be strained from the stools. The percent of patients found to harbor residual stones in the common duct declines steadily each day that passes hetween onset and operation. This also suggests that these stones are passing spontaneously as the attack subsides, but no one can be sure that all have passed. Therefore a cholangiogram is always needed when the gallbladder is removed. Any stones still rattling around in the common bile duct are not the stones that caused this attack. They are the followers that will cause the subsequent bouts if not removed. A small number of patients with severe attacks develop pancreatic necrosis and require later debridement, lavage, and drainage of infected necrotic tissue. This was not altered by early open operation to remove the stones left behind in the common duct. Autopsied patients who died of gallstone pancreatitis commonly had a necrotic pancreas without an impacted ampullary stone.4 Presumably the stone passed early in the course of the disease but the damage to the pancreas had been done. Most of the little we know about the cause of gallstone pancreatitis comes from animal studies. These show that the primary determinant of the severity of pancreatic inflammation is the initial exocrine leak into the parenchyma of the gland. The fact that early stone removal by operation does not alter the course of pancreatitis lends support to this concept. Whether or not early ERCP can reduce pancreatic necrosis as Neoptolemos believes’ remains to be seen. For the present, early or immediate ERCP should be limited to the severe cases, those with septic cholangitis, and those not improving as expected. At laparoscopic cholecystectomy a cholangiogram should regularly be performed to determine whether any stones re0002-961 O/96/$1 PII SOOO2-9610(96)00104-3
5.00
225
main. This will be negative most of the time when operation has been delayed to allow recovery from the acute symptoms. However, if stones are present these can usually be removed by laparoscopic techniques, which are improving and still evolving.6 If unsuccessful, postoperative ERCP and sphincterotomy or open choledochotomy is indicated. Emergency or preoperative ERCP should become infrequent, and postoperative ERCP performed only when needed for known therapeutic reasons. In the overwhelming majority of cases the necessary definitive surgery can be performed by the same surgeon at the same time in the same setting. In the future, laparoscopic cholecystectomy combined with laparoscopic cholangiography and bile duct clearance will probably become as commonplace as open cholecystectomy and common bile duct exploration has been in the past.’
REFERENCES 1. Kelly TR, Elliott DW. Proper timing of surgery for gallstone pancreatitis. AmJ Surg. 1990;159:361-362. 2. Fan TS, Lai ECS, Mok FPT, et al. Early treatment of acute biliary pancreatitis by endoscopic papillotomy. NEJM. 1993;328:228-232. 3. Neoptolemos JP, Carr-Locke DL, London NJ, et al. Controlled trial of urgen endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lmcet. 1988;29:979-983. 4. Kelly TR, Wagner DS. Gallstone pancreatitis: a prospective randomized trial of the timing of surgery. Surgery. 1988;104:600-605. 5. Neoptolemos JP. Endoscopic sphinceterotomy in acute gallstone pancreatitis. Br J Surg. 1993;80:547-549. 6. Roush TS, Traverso LW. Management and long-term follow-up of patients with positive cholangiograms during laparoscopic cholecystectomy. Am J Lug. 1995;169:484-487. 7. Soper NJ, Brunt M, Gallery Ml’, et al. Role of laparoscopic cholecystectomy in the management of gallstone pancreatitis. Am J Surg. 1994;167:42-51.
EDITORIAL
COMMENT
The patient presenting with gallstone pancreatitis has traditionally been treated with open cholecystectomy and cholangiogram following resolution of the acute pancreatitis, but usually during the same hospitalization. Presently, the patient may be treated with preoperative ERCP and removal of stones, intraoperatively with laparoscopic or open common bile duct exploration, or postoperatively with ERCP and stone removal for those identified as having common duct stones during laparoscopic cholecystectomy. There are even those who recommend leaving stones identified at laparoscopic cholangiography in place for spontaneous passage, if they are small. Preoperative ERCP for gallstone pancreatitis is of unclear value in patients with mild or resolving pancreatitis, but this is not the case for severe and/or worsening gallstone pancreatitis. There are prospective randomized data from controlled clinical trials that demonstrate markedly reduced mortality if preoperative urgent ERCP is performed in this select group of patients. Neoptolemos et al, in the United Kingdom, studied 121 patients with urgent ERCP being performed in 59 patients within 72 hours in one group treated with urgent ERCP compared with 62 patients in another group treated conservatively with observation and subsequent cholecystectomy. There were fewer complications and a lower mortality among patients treated with urgent ERCP. This was partic226
THE AMERICAN
JOURNAL
OF
SURGERY”
VOLUME
172
ularly notable among those in whom the pancreatitis was severe. Among the 53 patients with severe pancreatitis, 6 of 25 treated with urgent ERCP had complications with 1 death (24% morbidity and 1.7% mortality), while those undergoing conventional treatment had complications in 17 of 28 with 5 deaths (61% morbidity and 17.9% mortality). Hospital stay was significantly shortened in the ERCP group (median, 9.5 vs 17 days).’ A second prospective randomized trial from San Diego demonstrated similar results in 70 consecutive patients. In this paper, no complications were attributal to ERCP or endoscopic sphincterotomy, and the 2 deaths in the series occurred in patients who had undergone conventional treatment without ERCP.’ In the subset of patients who present with both acute pancreatitis and cholangitis, there is again definite evidence that early ERCP may reduce morbidity and mortality. Among patients with urgent preoperative ERCP, the mortality rate was 4%, while it was 33% among those treated without ERCP.’ Fan et al also report a benefit of obtaining early ERCP in the course of severe acute gallstone pancreatitis agam with benefit limited to certain subsets of the patients.4 Another study that would suggest that ERCP might be useful in reducing mortality and severe gallstone pancreatitis comes from autopsy data. Carter reported a postmortem series of 132 cases of fatal acute pancreatitis. One-third of these cases were first diagnosed as being of gallstone etiology at the time of the postmortem.5 Earlier identification of the gallstone etiology may have allowed intervention and improved outcome in severe pancreatitis. It is sometimes difficult to identify the biliary origin of pancreatitis with noncholangiographic studies. In a series of 50 patients assessed with respect to biliary origin of pancreatitis, CT and ultrasound could not reliably make the diagnosis of biliary origin of the pancreatitis.6 Lux et al also demonstrated the relative inability of standard laboratory tests and ultrasound to differentiate biliary and alcoholic pancreatitis7 In this study of 44 patients, half with biliary and half with alcoholic origin of the disease, laboratory tests were not useful in discriminating alcoholic vs gallstone pancreatitis patients, and ultrasound was found to have a 68% sensitivity. Given the fact that ERCP can be used for immediate therapeutic intervention, with improved outcome, it is clearly a useful test for those with severe and/or worsening pancreatitis suspected to be of gallstone etiology. In summary, while a variety of approaches may be successful for mild or improving pancreatitis, those with severe and/or worsening pancreatitis, especially those suspected to be of gallstone etiology, should probably undergo urgent ERCP. Given the inability of ultrasound and laboratory determinants to entirely differentiate gallstone and alcoholic pancreatitis, it may be wise to extend this indication to all patients with severe and/or worsening pancreatitis. In patients with a mild or resolving pancreatitis, it is currently our approach to avoid preoperative ERCP and proceed directly with laparoscopic cholecystectomy and cholangiog raphy. Management of identified stones would depend on local expertise, but either laparoscopic common duct stone removal or postoperative ERCP with stone removal are acceptable alternatives. I do not personally feel that it is wise to leave identified stones for postoperative spontaneous pasSEPTEMBER
1996
1 MANAGEMENT
sage. In our new era of laparoscopic surgery, this is clearly an evolving field and further extensive prospective studies will be necessary to entirelv delineate the best management for these Datients. It is cldar that the last chapter Las not been written in the management of common bile duct stones and gallstone pancreatitis. Gary C. Vitale, MD Department of Surgery University of Louisville Louisville, Kentucky
REFERENCES 1. Pitt HA, Gomes AS, Lois JF, Mann LL, Deutsch LS, Longmire WP, Jr. Does preoperative hiliary drainage reduce operative risk or increase hospital cost? Ann Sq. 1985;201:545-553.
THE
AMERICAN
OF
GALLSTONE
PANCREATITIS/KELLY
AND
ELLIOT
2. Seyrig JA, Liguory C, Medun B, Ink 0, Buffet C. Endoscopy in tumors of the Oddi region. Diagnostic and therapeutic possibilities. Gastroenterol Clin Bd 1985;9:103-108. 3. Huibregtse K, Schneider B, Rauws E, Tyrgat GN. Carcmoma of the ampulla of Vater. The role of endoscoplc drainage. Slnrg Endosc. 1987;1:79-52. 4. Fan ST, Lai ECS, Mok FPT, et al. Early treatment of acute biliary pancreatitis by endoscoplc pap&>tomy. NE/M. 1991;328:228-232. 5. Nakao NL, Siegal JH, Stenger R], Gelh AM. Tumours of the ampulla of Vater: early diagnosis by intra-ampullary biopsy during endoscopx cannulatlon. Two case presentations and a rewew of the literature. Gastroenterolqy. 1982;83:459-464. 6. Safrany L. Duodenoscopy and hiopsy: irxernational workshop. In: Classen M, Geenen J, Kawai K, eds. T/w Papila of Vater ad Its Diseases. Baden-Baden: Witzstrock, 197966-T 1. 7. Bourgeois N, Dunham F, Verhest A, Cremer M. Endoscopic biopsies of the papilla of Vater at the time of endoscopic sphincterotomy: difficulties m interpretation. Gastrointest Edosc. 1984;30:163-166.
JOURNAL
OF SURGERY@
VOLUME
172
SEPTEMBER
1996
227