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Surgical management of pancreas divisum
Surgical Management of Pancreas Divisum
Marc Cooperman, MD, Columbus, Ohio John J. Ferrara, MD, Columbus, Ohio John J. Fromkes, MD, Columbus, Ohio Larry C. Carey, MD, Columbus, Ohio
The normal adult pancreatic ductal system was well delineated by 16th and 17th century anatomists, culminating with the descriptions by Wirsung and Santorini of the major and minor ducts, respectively. Although later investigators observed various anomalies of ductal anatomy, it was not until 1903 that Opie [I], during investigation of gallstone pancreatitis, noted a 10 percent incidence of an unfused ductal system in an otherwise fused pancreas (Figure 1). Several years later he coined the term pancreas diuisum to describe this anomaly [Z]. Twentieth century anatomists confirmed the existence of this anomaly in 2 to 10 percent of autopsy dissections [3-B]. In the early 1970s endoscopic retrograde cholangiopancreatography achieved widespread use in the diagnosis of pancreatic disease. Unfused pancreatic ductal systems were found in approximately 3 percent of cannulations [9], and the term pancreas diuisum was revived. However, only recently has this anomaly been suggested as an etiologic factor in recurrent pancreatitis [IO-131. Furthermore, Gregg [14] was able to ameliorate symptoms of pancreatitis by operative treatment of pancreas divisum in several patients. Yet the clinical significance of pancreas divisum continues to be controversial. It is our belief that recurrent pancreatitis in patients with this anomaly can be due to stenosis at the entrance of the duct of Santorini into the duodenum and that operative treatment directed there will relieve the disease. This report presents our initial experience with the operative treatment of pancreas divisum.
From The Departments of Surgery and Medicine, The Ohio State University Hospitals, Columbus, Ohio. Requests for reprints should be addressed to Marc Cooperman, MD, Department of Surgery, Ohio State University Hospitals, 410 West Tenth Avenue, Columbus, Ohio 43210. Presented at the 22nd Annual Meeting of The Society for Surgery of the Alimentary Tract, New York, New York, May 19-20, 1981.
Volume 143, January
1932
Patients and Methods
In a 30 month period, 314 endoscopic retrograde cholangiopancreatographic procedures with successful cannulation of the pancreatic duct were performed at the Ohio State University Hospitals. Pancreas divisum, characterized endoscopically by visualization of only the uncinate process when dye is introduced into the duct of Wirsung (Figure 2), was identified in 21 patients (6.7 percent). Sixteen of these patients had previously undergone thorough investigation for epigastric pain. Eight had had at least two documented attacks of acute pancreatitis. All were asymptomatic between illnesses. Two subsequently admitted alcohol abuse and were excluded from further evaluation. In the remaining six patients there were no identifiable etiologic factors other than pancreas divisum to account for pancreatitis. Three of the six had had previous cholecystectomy, and the other three had had normal oral cholecystograms and a normal-appearing gallbladder when endoscopic retrograde cholangiopancreatography was performed. All six patients, one man and five women aged 24 to 67 years, underwent laparotomy. The pancreas appeared grossly normal in all patients. No patient had changes suggestive of chronic pancreatitis. Cholecystectomy was performed in the three patients whose gallbladders had not been previously removed. Cholelithiasis was confirmed in one patient, despite the negative findings on preoperative evaluation, and cholecystectomy only was performed in this patient. No stones were found in the other two gallbladders removed. Sphincteroplasty of the orifice of the duct of Santorini was performed in four patients. The second portion of the duodenum was opened longitudinally and the minor papilla with the orifice of the duct of Santorini was located. The orifice of the duct of Santorini was stenotic in all four patients, admitting only a small lacrimal probe with difficulty. Progressively larger probes were used to dilate the ductal orifice. Dilatation was continued until a size 8 French catheter could he introduced into the duct. A groove director was then inserted into the duct and the ductal orifice was opened with a Pott’s scissors. The ductal and duodenal mucosa was carefully approximated with interrupted sutures of 4-10 polyglycolic acid suture. When sphinctero-
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Superior Mesenteric
Superior Mesenteric
A.
V.
F@te 1. A&M pancreasdemonstratingnoms&n of the &nsal and ventral ductal systems. A. = artery; V. = vein.
plasty was completed, the size 8 French catheter passed easily into the duct of Santorini. In three of the four patier& sphincteroplasty was performed on the duct of Wirsung as well. In the sixth patient, operative pancreatography showed the duct of Santorini to be markedly dilated. Pancreaticojejunostomy rather than sphincteroplasty was performed in this patient. Results All six patients had uncomplicated postoperative courses, and they have now been followed for 7,11, 12,13,18 and 24 months. The patient who had small gallstones and underwent cholecystectomy only has been asymptomatic for 11 months with no further attacks of pancreatitis. Of the four patients undergoing sphincteroplasty of the duct of Santorini, three are doing well at 12,13 and 18 months since operation with no recurrent episodes of pancreatitis. One patient had recurrent pancreatitis after sphincteroplasty and underwent repeat endoscopic retrograde cholangiopancreatography, which demonstrated a stricture at the site of the Santorini sphincteroplasty. She underwent reoperation and this finding was confirmed. Sphincteroplasty was again performed and she has had no further attacks of documented pancreatitis in the ensuing 4 months, although she continues to have epigastric discomfort. The patient who underwent pancreaticojejunostomy developed pancreatitis 4 months postoperatively. However, in the 20 months since, he has remained entirely asymptomatic. Comments Pancreas divisum is best described in light of the embryologic development of the human pancreas [15] during the first 8 weeks of gestation (Figure 3). The normal adult pancreas results from fusion of two endodermal primordia. The ventral pancreas originates as a diverticulum from the liver bud, while the larger, faster-growing dorsal primordium arises from the duodenum. As the liver and hepatic ductal sys-
108
Figure 2, Endoscopiccannuiationof the major ampuiia. Dye injected into the common bile duct showed normal filling of the gallbladder and hepatk ducts. Subsequentinjection of the pancreatk duct visualizedtM uncinateptvcess of the pancreasakna (arrow).
terns grow, the ventral pancreatic bud rotates clockwise to a position posterior to the duodenum and in apposition to the dorsal pancreatic bud. The two primordia fuse and the duodenum rotates to the right, thereby reaching its place in the retroperitoneum as a C-shaped loop of bowel crsdling the pancreas. During fusion of pancreatic acinar cells, the dorsal and ventral ductal anlagen unite. The main duct of Wirsung results from fusion of the proximal ventral duct with the more distal portion of the dorsal pancreatic duct; this duct usually shares the major duodenal papilla of Vater with the common bile duct. The proximal portion of the dorsal duct of Santorini often persists as an accessory pancreatic duct when it enters the duodenum through a more cephalad minor pancreatic papilla. The process was well described in a discussion of pancreatic anatomy by Opie [I] at the Congress of American Physicians and Surgeons in 1903. He noted that in 10 percent of his autopsy dissections the dorsal and ventral pancreatic ducts had failed to fuse. Several years later, in a chapter on pancreatic anomalies, Opie [2] first used the term pancreas diuisum to describe a situation in which there is “. . . absence of lobules of parenchyma about the duct of Wirsung or its branches for a short distance (which) has caused a division of the gland into two parts.” While this term remained buried in the literature for most of the 20th century, anatomists such as Baldwin
The American
Journal of Surgery
Pancreas Division
F@/re3.A, ort#nofthedorsal 6, croCkwise rota&n of-the ventral bud resutts in this smatterportkmofthepancreas assumtnga podthmcwdal to (C) thelafger dorsal pancre& bud. D,?uskn oftheductal systems and parenchyma of the two pancreatk anlagen.
Major Papilla /
[3], Milbourn [4,5], Berman et al [6], and Dawson and Langman [7] continued to note a 4 to 10 percent incidence of nonunion of ductal systems in necropsy specimens. By the middle of the century surgeons had become increasingly adept at operating on patients with pancreatic lesions. Their use of operative pancreatography led to renewed interest in the definition of pancreatic ductal anatomy. Birnstingl [8] described his observations on radiographic visualization of the duct system in autopsy specimens and coincidentally identified ductal nonunion in 5 percent. Since these were autopsy studies, however, no clinical significance was attached to this rediscovery. By the early 197Os, endoscopic retrograde cholangiopancreatography had become an established method for the study of patients with suspected pancreaticobiliary disease. Data from large series accumulated, including those of Phillip et al [9] reported in 1974. In 2.7 percent of their pancreatic duct cannulations through the papilla of Vater, only a small portion of the duct equivalent to that draining the uncinate process was visualized. Results from other studies confirmed this finding, and the term pancreas diuisum was resurrected. Riisch et al [16] warned endoscopists of the clinical importance of recognition, since the instillation of dye into an unexpectedly foreshortened duct could precipitate
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1982
an episode of pancreatitis. Cotton [17] underscored this finding, adding that once divisum is shown, an attempt at cannulating the minor papilla should be made. Soon thereafter, investigators began to suspect that pancreas divisum might have further clinical significance as an etiologic factor in pancreatitis. Kruse [13] noted that while only 6 percent of patients who had undergone endoscopic retrograde cholangiopancreatography in his series demonstrated divisum, this small group had a 20 percent incidence of established chronic pancreatitis. Cotton and Kizu [IO] suggested that inadequate drainage through Santorini’s duct may be important in patients with pancreatitis who have divisum. Cotton [12] later reported a 3.6 percent overall incidence of divisum in his series of patients who had undergone endoscopic retrograde cholangiopancreatography, but a 25.6 percent incidence in patients with heretofore unexplained recurrent pancreatitis. Several investigators have shown that although patients with pancreas divisum are often asymptomatic, they have a higher than normal incidence of recurrent attacks of pancreatitis. Inadequate drainage of the dorsal pancreas through the minor sphincter is thought by most to be responsible. Several attempts have been made at surgical therapy of pancreas divisum in the symptomatic
Cooperman et al
patient. Cotton and Kizu [IO] were able to perform endoscopic sphincterotomy on the minor papilla with what was stated to be good short-term results in one patient. Heiss and Shea [II] employed sphincterotomy of both papillas along with cholecystectomy in two patients and 85 percent pancreatectomy in a third patient with chronic pancreatitis. Gregg [14], in addition to using double sphincteroplasty, suggested that a connective tissue plane separates the two portions of the pancreas in divisum; thus, it should be possible to identify and resect the diseased portion alone. The number of patients in each of these series is small, follow-up has been limited, and the long-term success rate with these procedures is unknown. Our approach to the patient with recurrent pancreatitis and pancreas divisum is based on the concept that this anatomic anomaly can be the sole etiologic factor in acute pancreatitis. However, it has been clearly shown that pancreas divisum may coexist with other causes of pancreatitis and may even be a incidental finding of endoscopic retrograde cholangiopancreatography performed for biliary tract disease in patients without a history suggestive of pancreatitis. Therefore, the patient in whom surgical treatment of pancreas divisum is planned must be selected carefully. All other causes of pancreatitis such as alcoholism, biliary tract disease, hypercalcemia, hyperlipidemia and ingestion of drugs known to produce pancreatitis must be carefully excluded. Only in patients in whom no cause of documented acute pancreatitis other than pancreas divisum can be found should operative treatment of the ductal anomaly be considered. Biliary tract disease must be excluded completely in these patients. If cholecystectomy has not been performed, the gallbladder should be removed. The gallbladder should be opened and carefully examined for small stones that may not have been detected on either oral cholecystography or endoscopic retrograde cholangiopancreatography. If cholelithiasis is confirmed, only cholecystectomy should be performed. Treatment of pancreas divisum should not be undertaken unless the patient has recurrent pancreatitis after correction of biliary tract disease. The one patient in our series in whom unsuspected gallstones were found has done well for 11 months after cholecystectomy alone, suggesting that biliary tract disease rather than pancreas divisum was the cause of recurrent attacks of acute pancreatitis. If the gallbladder is normal or has been removed earlier, the duodenum is opened longitudinally and the minor papilla with the orifice of the duct of Santorini is located. This orifice has been uniformly found to be stenotic, admitting only a small lacrimal probe. This lends support to the concept that pancreatitis occurring in patients with pancreas divisum is due to impaired drainage of the aberrant duct of Santorini. The narrow orifice of Santorini makes the
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operation technically difficult. Cannulation of the orifice may be difficult. Progressive dilatation of the duct is necessary before a grooved director may be inserted. At the completion of ductoplasty, the orifice should be large enough to admit a size 8 French dilator with ease. Before sphincteroplasty is undertaken, operative pancreatography should be performed to ensure that there is no distal obstruction in the duct of Santorini and that the duct is not markedly dilated from chronic pancreatitis. If a dilated duct is encountered, as was the case in one patient in this series, pancreaticojejunostomy rather than sphincteroplasty should be performed. After the orifice of the duct of Santorini has been dilated and incised, it is important to reapproximate the ductal and duodenal mucosa carefully to avoid subsequent stricture formation. A stricture did develop at the site of sphincteroplasty in one patient in this series, and pancreatitis recurred. Stricture of the sphincteroplasty was documented both by endoscopic retrograde cholangiopancreatography and at reoperation. The fact that recurrent pancreatitis followed reobstruction of drainage from the duct of Santorini further supports the concept that this is the underlying mechanism in the development of pancreatitis in patients with pancreas divisum. The use of magnifying loops and microsurgical techniques may improve suture placement and avoid scarring with subsequent stricture formation. In the first three of the four patients undergoing sphincteroplasty on the duct of Santorini, ductoplasty was also performed on the duct of Wirsung, as it was not possible to tell from inspection whether the dorsal or ventral pancreas was the source of pancreatitis. However, based on the consistent finding of a stenotic orifice of the duct of Santorini, sphincteroplasty on the duct of Santorini alone is probably sufficient. The one patient in whom only this procedure was performed has done well without evidence of recurrent pancreatitis. Major pancreatic resection should be reserved for patients in whom either sphincteroplasty or drainage procedures have failed. If chronic pancreatitis has developed in the presence of a greatly dilated duct, pancreaticojejunostomy offers the advantage over near-total or total pancreatectomy of preserving existing exocrine and endocrine pancreatic function. Experience with the operative treatment of pancreas divisum is limited and the follow-up period is relatively brief. However, the preliminary results reported in this series are encouraging. The prevention of recurrent pancreatitis lends support to the concept that stenosis at the orifice of Santorini is the cause of recurrent pancreatitis in these patients and demonstrates that this anomaly is amenable to surgical correction. Patients, however, must be selected carefully. Only those proved to have the ductal
The American
Journal Of Surgery
Pancreas
anomaly with documented acute pancreatitis and in whom all other causes of pancreatitis have been excluded should be considered for operation. Summary Pancreas divisum is a congenital anatomic variant characterized by nonunion of dorsal and ventral pancreatic ducts in an otherwise fused pancreas. Of 21 patients with divisum documented by endoscopic retrograde cholangiopancreatography, 6 (28 percent) were found to have no reason other than divisum to account for multiple attacks of pancreatitis. Cholelithiasis was present in one patient, who remains free of recurrent pancreatitis after cholecystectomy only. The remaining five patients underwent surgical treatment directed at pancreas divisum in the belief that stenosis of the duct of Santorini at the entrance into the duodenum is responsible for recurrent attacks of pancreatitis. Four of five have done well with follow-up of 12, 13, 18 and 28 months. Successful sphincteroplasty of the duct of Santorini appears to prevent recurrent attacks of pancreatitis due to pancreas divisum. Pancreaticojejunostomy is reserved for those with markedly dilated ducts secondary to chronic pancreatitis. References 1. Opie E. The anatomy of the pancreas. Johns Hopkins Hosp Bull 1903;150:229-32. 2. Opie E. Disease of the pancreas: its cause and nature. Philadelphia: JB Lippincott, 1910:29. 3. Baldwin WM.The pancreatic ducts in man, together with a study of the microscopic structure of the minor duodenal papilla. Anat Ret 1911;5:197-228. 4. Millbourn E. On the extractory ducts of the pancreas in man, with special reference to their relations to each other, to the common bile duct and to the duodenum. Acta Anat 1950; 9: l-34. 5. Millbourn E. Calibre and appearance of the pancreatic ducts and relevant clinical problems. Acta Chir Stand 1959; 118:286. 6. Berman LM, Prior JT, Abramam SM, Zeigler DD. A study of the pancreatic duct system in man by the use of vinyl acetate casts of postmortem preparations. Surg Gynecol Obstet 1960;110:391-403, 7. Dawson W, Langman J. An anatomic-radiological study on the pancreatic duct pattern in man. Anat Ret 1961;139:5968. 8. Birnstingl M. A study of pancreatography. Br J Surg 1959;47: 128-39. 9. Phillip J. Koch H, Classen M. Variations and anomalies of the papilla of Vater, the pancreas, and the biliary duct system. Endoscopy 1974;6:70-7. 10. Cotton PB, Kizu M. Malfusion of dorsal and ventral pancreas; a cause of pancreatitis? Br Sot Gastroenterol 1977;18: A400. 11. Heiss FW, Shea JA. Association of pancreatitis and variant ductal anatomy. Am J Gastroenterol 1978;70:158-62. 12. Cotton PH. Congenital anomaly of pancreas divisum as cause of obstructive pain and pancreatitis. Gut 1980;21:105-14. 13. Kruse A. Pancreas divisum: a significantly higher incidence in chronic pancreatitis? Stand J Gastroenterol 1977; 12:52. 14. Gregg JA. Pancreas divisum: its association with pancreatitis. Am J Surg 1977;134:539-43. 15. Skandalakis JC, Gray SW. Rowe JS, Skondalakis LJ. Surgical
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anatomy of the pancreas. Personal communication. 16. Rosch N, Koch H, Schaffner 0, Drinling L. The clinical significance of the pancreas divisum. Gastrointestinal Endosc 1976;22:206-7. 17. Cotton PH. Progress report: ERCP. Gut 1977;18:316-41.
Discussion Abdool R. Moossa (Chicago, IL): This is a provocative preliminary report. I should reiterate some words of caution from the report: the number of patients is small and the follow-up short. Most persons with pancreas divisum have no problem whatsoever. It is not an anomaly, it is just a normal variant. I have some difficulty in accepting the concept of relative obstruction to pancreatic drainage at the papilla of Santorini which can be relieved by appropriate papillotomy. If such an obstruction exists, why is not the proximal duct demonstrably dilated? If such an obstruction exists, the attacks of pancreatitis should occur when the gland is maximally stimulated, that is, after meals. In the authors’ observations these attacks occur once or twice a year, and never in relation to meals. I would like to ask Dr. Cooperman whether he has attempted to stimulate the pancreas in these patients by injecting secretin or cholecystokinin-pancreozymin to see whether he can prove his thesis by precipitating an attack of pancreatitis. Robert Shapiro (Boston, MA): This report closely mirrors a similar study done by James Richter, Andrew Warshaw and myself at the Massachusetts General Hospital. We reviewed all the endoscopic pancreatograms done over a 7 year period in our group and segregated them according to the indication for the procedure. The procedure was performed in 519 patients, and this represented an 86 percent success rate when pancreatography was intended. Although the overall incidence of pancreas divisum was 5 percent, in the patients with documented pancreatitis the incidence was 12 percent, compared with 2.9 percent in patients studied primarily for biliary tract disease (p >0.005). This suggests that pancreas divisum in some way predisposes to the occurrence of pancreatitis. We subjected nine patients to sphincteroplasty of the accessory ampulla. Three patients who had the procedure done because of intractable abdominal pain obtained no benefit. Of the six patients who had documented pancreatitis, five had good to excellent results. David Fromm (Syracuse, NY): I have three questions. My recollection of Dr. Cotton’s series in Gut a few years ago is that in about 50 percent of patients he could not find the opening of the duct of Santorini endoscopically. What do you do at operation to locate the accessory ampulla, and have you had any difficulties? What is the normal size (that is, the internal diameter) of the accessory ampulla when it is found at operation? Thomas T. White (Seattle, WA): I can partly answer the last question by saying that you can use a size 50 polyethylene catheter in many instances, and in most instances you can’t get anything much bigger than that in the sphincter of Santorini. I would like to ask the authors how high the amylase level was in these patients. We did several of this type of sphincterotomy procedures on the accessory duct in the late 1960s but unfortunately they did not have a long-term effect.
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I agree with the authors that if the duct is dilated some other procedure such as pancreaticojejunostomy should be carried out because most of these patients have general dilatation of the ductal system. John W. Harmon (Washington, D.C.): I want to relate some recent Army experience with sphincteroplasty for pancreas divisum. Major Bill Traverso performed two of these procedures at Letterman, and both patients had recurrence within 1 year. So, for those thinking of going home and doing some of these, I want to warn you that these two were done in what was apparently a satisfactory technical manner and both patients had recurrent pain within 1 year. Alfred Cuschieri (Dundee, Scotland): It is assumed that there is no sphincter around the accessory papilla from the available evidence, as far as I know. Can those who are doing sphincteroplasty of the accessory papilla produce evidence for the existence of a sphincter in this situation? Second, it is not right to try to establish a world registry for this anomaly, in order to find the natural history before the retrospective studies are used to associate pancreas divisum with the disease process? George L. Nardi (Boston, MA): I agree with some of the commentators who said it is difficult to say what size the normal orifice is. We are not sure about that with the duct of Wirsung either. Roughly one third of the patients we see have clinical pancreatitis of idiopathic origin. Possibly one third of persons with pancreas divisum can have the disease without necessarily incriminating the lack of ductal fusion. In the four patients I have operated on with this condition, I have a 50 percent batting average: two distal pancreatectomies with one good result, and two double sphincteroplasties with one good result. I did pancreaticoduodenal resection in one of these patients, figuring obstruction was the cause. The patient was not cured whatsoever by a so-called Whipple operation, and a very careful dissection of the entire pancreas by our pathologist failed to reveal any abnormalities whatsoever; vascular, parenchymal or ductal. Daniel Paloyan (Glenview, IL): I believe that these patients should be studied carefully both pre- and postoperatively with pancreatic secretory provocative tests. Another suggestion is that at operation, to further establish what is going on, a small distal pancreatectomy may be performed with a catheter introduced into the tail of the pancreas into the duct. This could be utilized not only for pancreatography but also to obtain flow and pressure measurements both before and after sphincteroplasty. In addition, a pancreatic biopsy could be obtained to assess the status of the pancreas at the time of the first operation. Furthermore, because this orifice is so small, I suggest that magnification techniques might allow not only a safe biopsy of the orifice of the duct of Santorini but also a more precise sphincteroplasty, perhaps with good long-term results. I agree that this is a real entity. I have had personal experience with three patients, two of whom did well after sphincteroplasty, and one of whom continued to have chronic pancreatitis. I think we need to have more information and a much longer follow-up before we can con112
clude the exact cause of this problem and assess long-term results. Marc Cooperman (closing): In response to Dr. Moossa’s comments, I agree with him that caution should be exercised in the selection of these patients for operation. We have reported on only a very small group of patients who were highly selected and in whom all other causes of pancreatitis had been ruled out. These patients, however, had been having recurrent attacks of clinically significant pancreatitis, in whom we felt operation was indicated. Dr. Moossa raised the question of the role of obstruction in a nondilated duct. I think part of the answer to this problem is that we are operating on these patients early in the course of the disease process. In the one patient who did have a dilated duct and who underwent distal pancreaticojejunostomy, recurrent episodes of pancreatitis had occurred for approximately 20 years. In this patient a dilated duct had developed, and it is reasonable to presume that if the other patients had been allowed to continue along their clinical course, changes suggestive of chronic pancreatitis might have developed in them as well. In answer to his question about whether stimulation was done to reproduce the symptoms of pancreatitis, we have not found the Nardi test helpful, and we have not used secretin infusion. Dr. Shapiro, I agree with you that careful patient selection will optimize the results of operative therapy. Dr. Fromm, we have had no difficulty finding the accessory duct at operation, using palpation to identify it. It is difficult for the endoscopist, however, to find this duct preoperatively, and usually it is not possible to successfully cannulate it. In these patients amylase levels have been elevated during periods of acute pancreatitis, which on clinical grounds and based on hyperamylasemia and elevated urinary amylase values are episodes of acute pancreatitis in every sense. However, between the acute episodes these patients have both been asymptomatic and their amylase levels returned to normal. In response to those discussants who mentioned recurrence, we also had one patient who developed recurrent pancreatitis, and at least in our case it was identified as a technical problem with restenosis of the duct. In order to adequately divide the orifice of the duct of Santorini it is necessary to progressively dilate the duct to the point where it will admit a size 8 French woven catheter. During this dilatation there is no question that trauma to the tissue occurs. It may very well be, as suggested by Dr. Paloyan, that the use of magnification and microscopic techniques will help improve the technical success of our operative efforts. In response to Dr. Nardi’s questions, I think procedures involving resection should be avoided except in patients in whom sphincteroplasty or drainage procedures have failed. The advantage of performing either sphincteroplasty or pancreaticojejunostomy is that the pancreatic substance is preserved and exocrine and endocrine function maintained. I agree with all of the discussants who have urged caution in this group of patients. This is a preliminary report. Further follow-up is needed. No one should go home and do papillotomy in these patients indiscriminately. I think pooling of data from different centers would be useful both in identifying the natural history of this disease and the results of operative intervention. The American Journal of Surgery
Marc Cooperman, MD, Columbus, Ohio John J. Ferrara, MD, Columbus, Ohio John J. Fromkes, MD, Columbus, Ohio Larry C. Carey, MD, Columbus, Ohio
The normal adult pancreatic ductal system was well delineated by 16th and 17th century anatomists, culminating with the descriptions by Wirsung and Santorini of the major and minor ducts, respectively. Although later investigators observed various anomalies of ductal anatomy, it was not until 1903 that Opie [I], during investigation of gallstone pancreatitis, noted a 10 percent incidence of an unfused ductal system in an otherwise fused pancreas (Figure 1). Several years later he coined the term pancreas diuisum to describe this anomaly [Z]. Twentieth century anatomists confirmed the existence of this anomaly in 2 to 10 percent of autopsy dissections [3-B]. In the early 1970s endoscopic retrograde cholangiopancreatography achieved widespread use in the diagnosis of pancreatic disease. Unfused pancreatic ductal systems were found in approximately 3 percent of cannulations [9], and the term pancreas diuisum was revived. However, only recently has this anomaly been suggested as an etiologic factor in recurrent pancreatitis [IO-131. Furthermore, Gregg [14] was able to ameliorate symptoms of pancreatitis by operative treatment of pancreas divisum in several patients. Yet the clinical significance of pancreas divisum continues to be controversial. It is our belief that recurrent pancreatitis in patients with this anomaly can be due to stenosis at the entrance of the duct of Santorini into the duodenum and that operative treatment directed there will relieve the disease. This report presents our initial experience with the operative treatment of pancreas divisum.
From The Departments of Surgery and Medicine, The Ohio State University Hospitals, Columbus, Ohio. Requests for reprints should be addressed to Marc Cooperman, MD, Department of Surgery, Ohio State University Hospitals, 410 West Tenth Avenue, Columbus, Ohio 43210. Presented at the 22nd Annual Meeting of The Society for Surgery of the Alimentary Tract, New York, New York, May 19-20, 1981.
Volume 143, January
1932
Patients and Methods
In a 30 month period, 314 endoscopic retrograde cholangiopancreatographic procedures with successful cannulation of the pancreatic duct were performed at the Ohio State University Hospitals. Pancreas divisum, characterized endoscopically by visualization of only the uncinate process when dye is introduced into the duct of Wirsung (Figure 2), was identified in 21 patients (6.7 percent). Sixteen of these patients had previously undergone thorough investigation for epigastric pain. Eight had had at least two documented attacks of acute pancreatitis. All were asymptomatic between illnesses. Two subsequently admitted alcohol abuse and were excluded from further evaluation. In the remaining six patients there were no identifiable etiologic factors other than pancreas divisum to account for pancreatitis. Three of the six had had previous cholecystectomy, and the other three had had normal oral cholecystograms and a normal-appearing gallbladder when endoscopic retrograde cholangiopancreatography was performed. All six patients, one man and five women aged 24 to 67 years, underwent laparotomy. The pancreas appeared grossly normal in all patients. No patient had changes suggestive of chronic pancreatitis. Cholecystectomy was performed in the three patients whose gallbladders had not been previously removed. Cholelithiasis was confirmed in one patient, despite the negative findings on preoperative evaluation, and cholecystectomy only was performed in this patient. No stones were found in the other two gallbladders removed. Sphincteroplasty of the orifice of the duct of Santorini was performed in four patients. The second portion of the duodenum was opened longitudinally and the minor papilla with the orifice of the duct of Santorini was located. The orifice of the duct of Santorini was stenotic in all four patients, admitting only a small lacrimal probe with difficulty. Progressively larger probes were used to dilate the ductal orifice. Dilatation was continued until a size 8 French catheter could he introduced into the duct. A groove director was then inserted into the duct and the ductal orifice was opened with a Pott’s scissors. The ductal and duodenal mucosa was carefully approximated with interrupted sutures of 4-10 polyglycolic acid suture. When sphinctero-
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Superior Mesenteric
Superior Mesenteric
A.
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F@te 1. A&M pancreasdemonstratingnoms&n of the &nsal and ventral ductal systems. A. = artery; V. = vein.
plasty was completed, the size 8 French catheter passed easily into the duct of Santorini. In three of the four patier& sphincteroplasty was performed on the duct of Wirsung as well. In the sixth patient, operative pancreatography showed the duct of Santorini to be markedly dilated. Pancreaticojejunostomy rather than sphincteroplasty was performed in this patient. Results All six patients had uncomplicated postoperative courses, and they have now been followed for 7,11, 12,13,18 and 24 months. The patient who had small gallstones and underwent cholecystectomy only has been asymptomatic for 11 months with no further attacks of pancreatitis. Of the four patients undergoing sphincteroplasty of the duct of Santorini, three are doing well at 12,13 and 18 months since operation with no recurrent episodes of pancreatitis. One patient had recurrent pancreatitis after sphincteroplasty and underwent repeat endoscopic retrograde cholangiopancreatography, which demonstrated a stricture at the site of the Santorini sphincteroplasty. She underwent reoperation and this finding was confirmed. Sphincteroplasty was again performed and she has had no further attacks of documented pancreatitis in the ensuing 4 months, although she continues to have epigastric discomfort. The patient who underwent pancreaticojejunostomy developed pancreatitis 4 months postoperatively. However, in the 20 months since, he has remained entirely asymptomatic. Comments Pancreas divisum is best described in light of the embryologic development of the human pancreas [15] during the first 8 weeks of gestation (Figure 3). The normal adult pancreas results from fusion of two endodermal primordia. The ventral pancreas originates as a diverticulum from the liver bud, while the larger, faster-growing dorsal primordium arises from the duodenum. As the liver and hepatic ductal sys-
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Figure 2, Endoscopiccannuiationof the major ampuiia. Dye injected into the common bile duct showed normal filling of the gallbladder and hepatk ducts. Subsequentinjection of the pancreatk duct visualizedtM uncinateptvcess of the pancreasakna (arrow).
terns grow, the ventral pancreatic bud rotates clockwise to a position posterior to the duodenum and in apposition to the dorsal pancreatic bud. The two primordia fuse and the duodenum rotates to the right, thereby reaching its place in the retroperitoneum as a C-shaped loop of bowel crsdling the pancreas. During fusion of pancreatic acinar cells, the dorsal and ventral ductal anlagen unite. The main duct of Wirsung results from fusion of the proximal ventral duct with the more distal portion of the dorsal pancreatic duct; this duct usually shares the major duodenal papilla of Vater with the common bile duct. The proximal portion of the dorsal duct of Santorini often persists as an accessory pancreatic duct when it enters the duodenum through a more cephalad minor pancreatic papilla. The process was well described in a discussion of pancreatic anatomy by Opie [I] at the Congress of American Physicians and Surgeons in 1903. He noted that in 10 percent of his autopsy dissections the dorsal and ventral pancreatic ducts had failed to fuse. Several years later, in a chapter on pancreatic anomalies, Opie [2] first used the term pancreas diuisum to describe a situation in which there is “. . . absence of lobules of parenchyma about the duct of Wirsung or its branches for a short distance (which) has caused a division of the gland into two parts.” While this term remained buried in the literature for most of the 20th century, anatomists such as Baldwin
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F@/re3.A, ort#nofthedorsal 6, croCkwise rota&n of-the ventral bud resutts in this smatterportkmofthepancreas assumtnga podthmcwdal to (C) thelafger dorsal pancre& bud. D,?uskn oftheductal systems and parenchyma of the two pancreatk anlagen.
Major Papilla /
[3], Milbourn [4,5], Berman et al [6], and Dawson and Langman [7] continued to note a 4 to 10 percent incidence of nonunion of ductal systems in necropsy specimens. By the middle of the century surgeons had become increasingly adept at operating on patients with pancreatic lesions. Their use of operative pancreatography led to renewed interest in the definition of pancreatic ductal anatomy. Birnstingl [8] described his observations on radiographic visualization of the duct system in autopsy specimens and coincidentally identified ductal nonunion in 5 percent. Since these were autopsy studies, however, no clinical significance was attached to this rediscovery. By the early 197Os, endoscopic retrograde cholangiopancreatography had become an established method for the study of patients with suspected pancreaticobiliary disease. Data from large series accumulated, including those of Phillip et al [9] reported in 1974. In 2.7 percent of their pancreatic duct cannulations through the papilla of Vater, only a small portion of the duct equivalent to that draining the uncinate process was visualized. Results from other studies confirmed this finding, and the term pancreas diuisum was resurrected. Riisch et al [16] warned endoscopists of the clinical importance of recognition, since the instillation of dye into an unexpectedly foreshortened duct could precipitate
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an episode of pancreatitis. Cotton [17] underscored this finding, adding that once divisum is shown, an attempt at cannulating the minor papilla should be made. Soon thereafter, investigators began to suspect that pancreas divisum might have further clinical significance as an etiologic factor in pancreatitis. Kruse [13] noted that while only 6 percent of patients who had undergone endoscopic retrograde cholangiopancreatography in his series demonstrated divisum, this small group had a 20 percent incidence of established chronic pancreatitis. Cotton and Kizu [IO] suggested that inadequate drainage through Santorini’s duct may be important in patients with pancreatitis who have divisum. Cotton [12] later reported a 3.6 percent overall incidence of divisum in his series of patients who had undergone endoscopic retrograde cholangiopancreatography, but a 25.6 percent incidence in patients with heretofore unexplained recurrent pancreatitis. Several investigators have shown that although patients with pancreas divisum are often asymptomatic, they have a higher than normal incidence of recurrent attacks of pancreatitis. Inadequate drainage of the dorsal pancreas through the minor sphincter is thought by most to be responsible. Several attempts have been made at surgical therapy of pancreas divisum in the symptomatic
Cooperman et al
patient. Cotton and Kizu [IO] were able to perform endoscopic sphincterotomy on the minor papilla with what was stated to be good short-term results in one patient. Heiss and Shea [II] employed sphincterotomy of both papillas along with cholecystectomy in two patients and 85 percent pancreatectomy in a third patient with chronic pancreatitis. Gregg [14], in addition to using double sphincteroplasty, suggested that a connective tissue plane separates the two portions of the pancreas in divisum; thus, it should be possible to identify and resect the diseased portion alone. The number of patients in each of these series is small, follow-up has been limited, and the long-term success rate with these procedures is unknown. Our approach to the patient with recurrent pancreatitis and pancreas divisum is based on the concept that this anatomic anomaly can be the sole etiologic factor in acute pancreatitis. However, it has been clearly shown that pancreas divisum may coexist with other causes of pancreatitis and may even be a incidental finding of endoscopic retrograde cholangiopancreatography performed for biliary tract disease in patients without a history suggestive of pancreatitis. Therefore, the patient in whom surgical treatment of pancreas divisum is planned must be selected carefully. All other causes of pancreatitis such as alcoholism, biliary tract disease, hypercalcemia, hyperlipidemia and ingestion of drugs known to produce pancreatitis must be carefully excluded. Only in patients in whom no cause of documented acute pancreatitis other than pancreas divisum can be found should operative treatment of the ductal anomaly be considered. Biliary tract disease must be excluded completely in these patients. If cholecystectomy has not been performed, the gallbladder should be removed. The gallbladder should be opened and carefully examined for small stones that may not have been detected on either oral cholecystography or endoscopic retrograde cholangiopancreatography. If cholelithiasis is confirmed, only cholecystectomy should be performed. Treatment of pancreas divisum should not be undertaken unless the patient has recurrent pancreatitis after correction of biliary tract disease. The one patient in our series in whom unsuspected gallstones were found has done well for 11 months after cholecystectomy alone, suggesting that biliary tract disease rather than pancreas divisum was the cause of recurrent attacks of acute pancreatitis. If the gallbladder is normal or has been removed earlier, the duodenum is opened longitudinally and the minor papilla with the orifice of the duct of Santorini is located. This orifice has been uniformly found to be stenotic, admitting only a small lacrimal probe. This lends support to the concept that pancreatitis occurring in patients with pancreas divisum is due to impaired drainage of the aberrant duct of Santorini. The narrow orifice of Santorini makes the
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operation technically difficult. Cannulation of the orifice may be difficult. Progressive dilatation of the duct is necessary before a grooved director may be inserted. At the completion of ductoplasty, the orifice should be large enough to admit a size 8 French dilator with ease. Before sphincteroplasty is undertaken, operative pancreatography should be performed to ensure that there is no distal obstruction in the duct of Santorini and that the duct is not markedly dilated from chronic pancreatitis. If a dilated duct is encountered, as was the case in one patient in this series, pancreaticojejunostomy rather than sphincteroplasty should be performed. After the orifice of the duct of Santorini has been dilated and incised, it is important to reapproximate the ductal and duodenal mucosa carefully to avoid subsequent stricture formation. A stricture did develop at the site of sphincteroplasty in one patient in this series, and pancreatitis recurred. Stricture of the sphincteroplasty was documented both by endoscopic retrograde cholangiopancreatography and at reoperation. The fact that recurrent pancreatitis followed reobstruction of drainage from the duct of Santorini further supports the concept that this is the underlying mechanism in the development of pancreatitis in patients with pancreas divisum. The use of magnifying loops and microsurgical techniques may improve suture placement and avoid scarring with subsequent stricture formation. In the first three of the four patients undergoing sphincteroplasty on the duct of Santorini, ductoplasty was also performed on the duct of Wirsung, as it was not possible to tell from inspection whether the dorsal or ventral pancreas was the source of pancreatitis. However, based on the consistent finding of a stenotic orifice of the duct of Santorini, sphincteroplasty on the duct of Santorini alone is probably sufficient. The one patient in whom only this procedure was performed has done well without evidence of recurrent pancreatitis. Major pancreatic resection should be reserved for patients in whom either sphincteroplasty or drainage procedures have failed. If chronic pancreatitis has developed in the presence of a greatly dilated duct, pancreaticojejunostomy offers the advantage over near-total or total pancreatectomy of preserving existing exocrine and endocrine pancreatic function. Experience with the operative treatment of pancreas divisum is limited and the follow-up period is relatively brief. However, the preliminary results reported in this series are encouraging. The prevention of recurrent pancreatitis lends support to the concept that stenosis at the orifice of Santorini is the cause of recurrent pancreatitis in these patients and demonstrates that this anomaly is amenable to surgical correction. Patients, however, must be selected carefully. Only those proved to have the ductal
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anomaly with documented acute pancreatitis and in whom all other causes of pancreatitis have been excluded should be considered for operation. Summary Pancreas divisum is a congenital anatomic variant characterized by nonunion of dorsal and ventral pancreatic ducts in an otherwise fused pancreas. Of 21 patients with divisum documented by endoscopic retrograde cholangiopancreatography, 6 (28 percent) were found to have no reason other than divisum to account for multiple attacks of pancreatitis. Cholelithiasis was present in one patient, who remains free of recurrent pancreatitis after cholecystectomy only. The remaining five patients underwent surgical treatment directed at pancreas divisum in the belief that stenosis of the duct of Santorini at the entrance into the duodenum is responsible for recurrent attacks of pancreatitis. Four of five have done well with follow-up of 12, 13, 18 and 28 months. Successful sphincteroplasty of the duct of Santorini appears to prevent recurrent attacks of pancreatitis due to pancreas divisum. Pancreaticojejunostomy is reserved for those with markedly dilated ducts secondary to chronic pancreatitis. References 1. Opie E. The anatomy of the pancreas. Johns Hopkins Hosp Bull 1903;150:229-32. 2. Opie E. Disease of the pancreas: its cause and nature. Philadelphia: JB Lippincott, 1910:29. 3. Baldwin WM.The pancreatic ducts in man, together with a study of the microscopic structure of the minor duodenal papilla. Anat Ret 1911;5:197-228. 4. Millbourn E. On the extractory ducts of the pancreas in man, with special reference to their relations to each other, to the common bile duct and to the duodenum. Acta Anat 1950; 9: l-34. 5. Millbourn E. Calibre and appearance of the pancreatic ducts and relevant clinical problems. Acta Chir Stand 1959; 118:286. 6. Berman LM, Prior JT, Abramam SM, Zeigler DD. A study of the pancreatic duct system in man by the use of vinyl acetate casts of postmortem preparations. Surg Gynecol Obstet 1960;110:391-403, 7. Dawson W, Langman J. An anatomic-radiological study on the pancreatic duct pattern in man. Anat Ret 1961;139:5968. 8. Birnstingl M. A study of pancreatography. Br J Surg 1959;47: 128-39. 9. Phillip J. Koch H, Classen M. Variations and anomalies of the papilla of Vater, the pancreas, and the biliary duct system. Endoscopy 1974;6:70-7. 10. Cotton PB, Kizu M. Malfusion of dorsal and ventral pancreas; a cause of pancreatitis? Br Sot Gastroenterol 1977;18: A400. 11. Heiss FW, Shea JA. Association of pancreatitis and variant ductal anatomy. Am J Gastroenterol 1978;70:158-62. 12. Cotton PH. Congenital anomaly of pancreas divisum as cause of obstructive pain and pancreatitis. Gut 1980;21:105-14. 13. Kruse A. Pancreas divisum: a significantly higher incidence in chronic pancreatitis? Stand J Gastroenterol 1977; 12:52. 14. Gregg JA. Pancreas divisum: its association with pancreatitis. Am J Surg 1977;134:539-43. 15. Skandalakis JC, Gray SW. Rowe JS, Skondalakis LJ. Surgical
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anatomy of the pancreas. Personal communication. 16. Rosch N, Koch H, Schaffner 0, Drinling L. The clinical significance of the pancreas divisum. Gastrointestinal Endosc 1976;22:206-7. 17. Cotton PH. Progress report: ERCP. Gut 1977;18:316-41.
Discussion Abdool R. Moossa (Chicago, IL): This is a provocative preliminary report. I should reiterate some words of caution from the report: the number of patients is small and the follow-up short. Most persons with pancreas divisum have no problem whatsoever. It is not an anomaly, it is just a normal variant. I have some difficulty in accepting the concept of relative obstruction to pancreatic drainage at the papilla of Santorini which can be relieved by appropriate papillotomy. If such an obstruction exists, why is not the proximal duct demonstrably dilated? If such an obstruction exists, the attacks of pancreatitis should occur when the gland is maximally stimulated, that is, after meals. In the authors’ observations these attacks occur once or twice a year, and never in relation to meals. I would like to ask Dr. Cooperman whether he has attempted to stimulate the pancreas in these patients by injecting secretin or cholecystokinin-pancreozymin to see whether he can prove his thesis by precipitating an attack of pancreatitis. Robert Shapiro (Boston, MA): This report closely mirrors a similar study done by James Richter, Andrew Warshaw and myself at the Massachusetts General Hospital. We reviewed all the endoscopic pancreatograms done over a 7 year period in our group and segregated them according to the indication for the procedure. The procedure was performed in 519 patients, and this represented an 86 percent success rate when pancreatography was intended. Although the overall incidence of pancreas divisum was 5 percent, in the patients with documented pancreatitis the incidence was 12 percent, compared with 2.9 percent in patients studied primarily for biliary tract disease (p >0.005). This suggests that pancreas divisum in some way predisposes to the occurrence of pancreatitis. We subjected nine patients to sphincteroplasty of the accessory ampulla. Three patients who had the procedure done because of intractable abdominal pain obtained no benefit. Of the six patients who had documented pancreatitis, five had good to excellent results. David Fromm (Syracuse, NY): I have three questions. My recollection of Dr. Cotton’s series in Gut a few years ago is that in about 50 percent of patients he could not find the opening of the duct of Santorini endoscopically. What do you do at operation to locate the accessory ampulla, and have you had any difficulties? What is the normal size (that is, the internal diameter) of the accessory ampulla when it is found at operation? Thomas T. White (Seattle, WA): I can partly answer the last question by saying that you can use a size 50 polyethylene catheter in many instances, and in most instances you can’t get anything much bigger than that in the sphincter of Santorini. I would like to ask the authors how high the amylase level was in these patients. We did several of this type of sphincterotomy procedures on the accessory duct in the late 1960s but unfortunately they did not have a long-term effect.
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I agree with the authors that if the duct is dilated some other procedure such as pancreaticojejunostomy should be carried out because most of these patients have general dilatation of the ductal system. John W. Harmon (Washington, D.C.): I want to relate some recent Army experience with sphincteroplasty for pancreas divisum. Major Bill Traverso performed two of these procedures at Letterman, and both patients had recurrence within 1 year. So, for those thinking of going home and doing some of these, I want to warn you that these two were done in what was apparently a satisfactory technical manner and both patients had recurrent pain within 1 year. Alfred Cuschieri (Dundee, Scotland): It is assumed that there is no sphincter around the accessory papilla from the available evidence, as far as I know. Can those who are doing sphincteroplasty of the accessory papilla produce evidence for the existence of a sphincter in this situation? Second, it is not right to try to establish a world registry for this anomaly, in order to find the natural history before the retrospective studies are used to associate pancreas divisum with the disease process? George L. Nardi (Boston, MA): I agree with some of the commentators who said it is difficult to say what size the normal orifice is. We are not sure about that with the duct of Wirsung either. Roughly one third of the patients we see have clinical pancreatitis of idiopathic origin. Possibly one third of persons with pancreas divisum can have the disease without necessarily incriminating the lack of ductal fusion. In the four patients I have operated on with this condition, I have a 50 percent batting average: two distal pancreatectomies with one good result, and two double sphincteroplasties with one good result. I did pancreaticoduodenal resection in one of these patients, figuring obstruction was the cause. The patient was not cured whatsoever by a so-called Whipple operation, and a very careful dissection of the entire pancreas by our pathologist failed to reveal any abnormalities whatsoever; vascular, parenchymal or ductal. Daniel Paloyan (Glenview, IL): I believe that these patients should be studied carefully both pre- and postoperatively with pancreatic secretory provocative tests. Another suggestion is that at operation, to further establish what is going on, a small distal pancreatectomy may be performed with a catheter introduced into the tail of the pancreas into the duct. This could be utilized not only for pancreatography but also to obtain flow and pressure measurements both before and after sphincteroplasty. In addition, a pancreatic biopsy could be obtained to assess the status of the pancreas at the time of the first operation. Furthermore, because this orifice is so small, I suggest that magnification techniques might allow not only a safe biopsy of the orifice of the duct of Santorini but also a more precise sphincteroplasty, perhaps with good long-term results. I agree that this is a real entity. I have had personal experience with three patients, two of whom did well after sphincteroplasty, and one of whom continued to have chronic pancreatitis. I think we need to have more information and a much longer follow-up before we can con112
clude the exact cause of this problem and assess long-term results. Marc Cooperman (closing): In response to Dr. Moossa’s comments, I agree with him that caution should be exercised in the selection of these patients for operation. We have reported on only a very small group of patients who were highly selected and in whom all other causes of pancreatitis had been ruled out. These patients, however, had been having recurrent attacks of clinically significant pancreatitis, in whom we felt operation was indicated. Dr. Moossa raised the question of the role of obstruction in a nondilated duct. I think part of the answer to this problem is that we are operating on these patients early in the course of the disease process. In the one patient who did have a dilated duct and who underwent distal pancreaticojejunostomy, recurrent episodes of pancreatitis had occurred for approximately 20 years. In this patient a dilated duct had developed, and it is reasonable to presume that if the other patients had been allowed to continue along their clinical course, changes suggestive of chronic pancreatitis might have developed in them as well. In answer to his question about whether stimulation was done to reproduce the symptoms of pancreatitis, we have not found the Nardi test helpful, and we have not used secretin infusion. Dr. Shapiro, I agree with you that careful patient selection will optimize the results of operative therapy. Dr. Fromm, we have had no difficulty finding the accessory duct at operation, using palpation to identify it. It is difficult for the endoscopist, however, to find this duct preoperatively, and usually it is not possible to successfully cannulate it. In these patients amylase levels have been elevated during periods of acute pancreatitis, which on clinical grounds and based on hyperamylasemia and elevated urinary amylase values are episodes of acute pancreatitis in every sense. However, between the acute episodes these patients have both been asymptomatic and their amylase levels returned to normal. In response to those discussants who mentioned recurrence, we also had one patient who developed recurrent pancreatitis, and at least in our case it was identified as a technical problem with restenosis of the duct. In order to adequately divide the orifice of the duct of Santorini it is necessary to progressively dilate the duct to the point where it will admit a size 8 French woven catheter. During this dilatation there is no question that trauma to the tissue occurs. It may very well be, as suggested by Dr. Paloyan, that the use of magnification and microscopic techniques will help improve the technical success of our operative efforts. In response to Dr. Nardi’s questions, I think procedures involving resection should be avoided except in patients in whom sphincteroplasty or drainage procedures have failed. The advantage of performing either sphincteroplasty or pancreaticojejunostomy is that the pancreatic substance is preserved and exocrine and endocrine function maintained. I agree with all of the discussants who have urged caution in this group of patients. This is a preliminary report. Further follow-up is needed. No one should go home and do papillotomy in these patients indiscriminately. I think pooling of data from different centers would be useful both in identifying the natural history of this disease and the results of operative intervention. The American Journal of Surgery