Pancreas Divisum

THE PANCREAS REVISITED I DIAGNOSTIC, CHRONIC PANCREATITIS

0039-6109/01 $15.00

+ .OO

PANCREAS DIVISUM Endoscopic Therapy Seth A. Cohen, MD, and Jerome H. Siegel, MD

Pancreas divisum is the most common congenital malformation of the pancreas and has been implicated as a cause of pancreatic disease. This article discusses the endoscopic therapy of symptomatic pancreas divisum.

PANCREATIC EMBRYOLOGY AND ANATOMY

During normal pancreatic development, the dorsal and ventral pancreatic buds fuse during the eighth week of gestation to form the main pancreatic duct (duct of Wirsung), which drains through the major papilla (Fig. 1A). A small duct (duct of Santorini, or the accessory duct) often persists between the main pancreatic duct and the minor papilla. Pancreas divisum occurs when the embryonic dorsal and ventral ducts fail to migrate and fuse abnormally (Fig. 1B). Pancreas divisum is estimated to be present in 5% to 7% of the population based on autopsy and endoscopic retrograde cholangiopancreatography (ERCP) studies. This results in two noncommunicating duct systems. The inferior portion of the head of the pancreas is drained by a rudimentary ventral duct through the major papilla, whereas most of the gland is drained by the dorsal duct through the minor papilla. A variant form, partial divisum, or functional divisum, occurs when the dorsal and ventral ducts are connected by a functionally inadequate duct, and most of the pancreatic secretion exits through the dorsal duct and the minor papilla (Fig. lo).”

From the Columbia University College of Physicians and Surgeons; the Division of Gastroenterology, St. Luke’s-Roosevelt Hospital Center, New York (SAC); the Albert Einstein College of Medicine; and the Division of Gastroenterology, Beth Israel Medical Center (JHS), New York, New York

SURGICAL CLINICS OF NORTH AMERICA

-

VOLUME 81 NUMBER 2 * APRIL 2001

467

468

COHEN & SIEGEL

Figure 1. Variations of pancreatic ductal anatomy. A, Normal. The main pancreatic duct drains through the major papilla. The remnant of the dorsal duct is patent and drains through the minor papilla. B, Pancreas divisum. A short, tapered, ventral duct drains only part of the head of the gland, whereas most of the pancreas is drained by the dorsal duct through the minor papilla. C, A variant of pancreas divisum in which no ventral duct is present. D, Functional pancreas divisum. The ventral duct communicates with the dorsal duct through a rudimentary connection.

HYPOTHESIS

In 1977, pancreas divisum was first proposed as the cause of idiopathic pancreatitis based on a higher observed prevalence of unexplained pancreatitis in patients with pancreas divisum than was expected.lO, l4 Pancreatitis is believed to result from resistance to the flow of pancreatic fluid through a small minor papilla. Although most endoscopists accept the proposition that pancreas divisum is a cause of idiopathic pancreatitis, this association remains controversial?,4, 6, 11-13,28, 29 Table 1summarizes the findings of some of the larger endoscopic series of pancreas divisum. Table 1. INCIDENCE OF PANCREAS DlVlSUM IN PATIENTS WITH PANCREATITIS AND IDIOPATHIC PANCREATITIS IN FIVE LARGE ERCP SERIES Cottonll

Number of cases of pancreas divisum Percentage of total cases Pancreatitis ("%) Idiopathic pancreatitis ("h) ERCP

=

47 5.8 16.4 25.6

S u ~ a w a ~D~e l h a ~ e ' ~ Bernard"

41 2.7 2.3 2.4

Endoscopic retrograde cholangiopancreatography.

304 5.7 6.9 5.3

137 7.5 27.8 50

Burtin4

62 5.9 6 12

PANCREAS DIVISUM

469

EVIDENCE TO IMPLICATE PANCREAS DlVlSUM AS A CAUSE OF PANCREATITIS

Several different lines of evidence support the hypothesis that pancreas divisum is the cause of pancreatitis as initially proposed by Cotton.*2First, there are epidemiologic data. The second line of evidence is the presence of stenosis of the minor papilla at surgery in some patients30 and the report of elevated dorsal duct pressures in a few patients with pancreas d i ~ i s u mThe . ~ ~third line of evidence comes from pathologic findings demonstrating segmental disease in the pancreas limited to the dorsal duct with healthy tissue in the ventral portion? The final, and the most important, line of evidence for the ductal obstruction hypothesis is the clinical data demonstrating the efficacy of a ductal drainage pr~cedure.~, 9, 15, *O, 21, 22, 27 For clinicians, symptomatic relief provided by ductal drainage is the "bottom line." ENDOSCOPIC DIAGNOSIS

Presumptive diagnosis of pancreas divisum can be made with opacification of the ventral duct during injection of the major papilla on endoscopic retrograde pancreatography. Definitive diagnosis depends on opacifying the dorsal duct through the minor papilla (Fig. 2). The ventral pancreatic duct appears as a short, "arborizing" duct system on pancreatography by the major papilla; this must be distinguished from a "cutoff" of the main pancreatic duct, which represents "pseudodivisum." In 15% to 24% of patients, the ventral duct is not demonstrable during pancreatography.' Pancreas divisum can be identified on MR cholangiopancreatography (MRCP) by following the main pancreatic duct to the accessory papilla and losing it at the genu. The head of the pancreas may appear abnormally prominent on CT scanning in patients with pancreas divisum, often prompting the radiologist to suggest correlation with pancreatography; this has been described as "pseudomass" of the pancreas.26 Dorsal ductography greatly increases the diagnostic yield when evaluating symptomatic patients with pancreas divisum and therefore is crucial. In one series, 106 nonalcoholic patients with pancreas divisum were evaluated by ERCP for pancreatitis, a suspected pancreatic mass, pain, or biliary disease. Among this group, 25% were found to have an abnormal dorsal duct. The most common findings were mild (9%) and advanced (14%) chronic pancreatitis, stricture, pancreatic stones (7%), pseudocyst (2%), and cancer (3%).' CLASSIFICATION OF PATIENTS WITH PANCREAS DlVlSUM

Pancreas divisum may be detected in several clinical situations, and correct classification of patients is crucial in selecting appropriate treatment. A complete evaluation of a symptomatic patient includes an ERCP with cholangiography and a dorsal pancreatogram, sphincter of Oddi (SO) manometry, and assessment for chronic pancreatitis. Pancreas divisum can exist as a normal variant and is of no consequence in asymptomatic people. Patients with symptomatic divisum generally are divided into three groups: (1) unexplained acute recurrent pancreatitis (ARP), (2) chronic pancreatitis, and (3) chronic abdominal pain in the absence of objective signs of pancreatic disease (pain only). Patients with pancreatitis should be subclassified as (1) those with pancreatitis of known cause or (2) those with "idiopathic" pancreatitis. Alcohol is a major cause of pancreatitis,

470

COHEN & SIEGEL

Figure 2. Radiographs showing the ventral and dorsal ducts in pancreas divisum. A, Endoscopic retrograde cholangiopancreatogram demonstrating a thin, arborizing ventral pancreatic duct and the common bile duct (CBD); the distal CBD is not opacified. B, Opacification of the dorsal duct, which crosses the CBD, in the same patient after cannulation of the minor papilla.

acute and chronic, and patients who imbibe alcohol need to be identified. Anecdotally, clinicians have observed that patients with divisum seem to be more susceptible to alcoholic-induced pancreatic disease and protected against biliary pancreatitis.”, 13, 28 Clinically, acute pancreatitis in patients with divisum tends to be mild and presents, with only modest elevations of amylase. Women are affected in greater numbers than men. Sonography or CT scanning may demonstrate edematous pancreatitis, and there is rarely evidence of pancreatic necrosis. The clinical course is self-limited, and patients usually respond to supportive care. In the authors’ experience, pseudocyst formation is the most common complication but occurs infrequently. Patients with chronic pancreatitis and divisum may present with recurrent episodes of pancreatitis or experience chronic pain. Steatorrhea, a reflection of exocrine insufficiency, occurs in less than one third of patients with chronic pancreatitis, and diabetes occurs even less frequently. Findings on pancreatography vary from mild to severe chronic pancreatitis.

PANCREAS DMSUM

471

Chronic abdominal pain in patients with pancreas divisum in the absence of pancreatitis tends to occur predominantly in young women. The pain is typically sharp and epigastric in location, radiates to the back, and is exacerbated by meals. Additional symptoms include nausea, vomiting, weight loss, and diarrhea. Most patients relate a long history of severe symptoms; however, many seem to have psychosocial abnormalities and low pain threshold, suggesting some overlap with irritable bowel syndrome. Many who manifest the pain syndrome of pancreas divisum become dependent on narcotics. In one reportz3from a treating referral center, 82 patients with pancreas divisum and abdominal pain were classified according to the cause of their pain. Thirty-two patients (39%) were found to have clinical conditions unrelated to pancreas divisum as explanation for their pain. These conditions included choledocholithiasis,cholangitis, dysfunction of the SO, peptic ulcer disease, and alcohol-related disease. Notably, there is an increased prevalence of SO dysfunction in patients with pancreas divisum. Thirty-three (40%) had recurrent attacks of pancreatitis, 11 (13%)had chronic pancreatitis, and 22 (27%) had no explanation other than pancreas divisum for recurrent acute pancreatitis. Seventeen patients (21%) with no other explanation except pancreas divisum for their symptoms had no documented history of pancreatitis. INDICATIONS FOR ENDOSCOPIC THERAPY

Asymptomatic patients with pancreas divisum require no treatment. In patients with documented pancreatitis, other possible causes need to be ruled out. When there is no other explanation of pancreatitis, endoscopic treatment is recommended even if the dorsal duct appears normal. In patients with abdominal pain and morphologic changes of chronic pancreatitis on pancreatography, medical management should be instituted, including abstinence, low-fat diet, high-dose pancreatic enzyme supplementation before meals, analgesics, and amitriptyline at bedtime. A trial of endoscopic therapy is warranted if the patient has recurrent, acute attacks of pancreatitis or significant ongoing pain despite medical management. This is particularly true when potentially treatable lesions, such as pancreatic stones, strictures, or communicating pseudocysts are present. Endoscopic therapy does not reverse the course of chronic pancreatitis. It may, however, decrease ductal pressures by allowing drainage and, thus, reduce attacks of pancreatitis and pain. Some do not recommend endoscopic treatment in patients with ductographic evidence of advanced chronic pancreatitis unless an obstructing lesion is present. Patients with pain and no documented history of pancreatitis present the most difficult management problems. The first goal is to rule out other treatable causes of abdominal pain, including peptic ulcer disease, biliary tract disease, SO dysfunction, and malignancy. Irritable bowel syndrome must be eliminated from the differential diagnosis with a reasonable degree of certainty. Initial treatment is medical management as outlined earlier. Some authorities recommend, if a patient remains significantly symptomatic (i.e., chronic pain, nausea, weight loss, and narcotic use), endoscopic treatment on an empiric basis, although this is controversial. SECRETIN TESTING

In an effort to develop a noninvasive test to predict patients who would respond to drainage, Catalan0 et a15proposed the endoscopic ultrasonography-

472

COHEN & SIEGEL

secretin stimulation test (EUS-secretin test). This is a modification of Warshaw but EUS is more accurate et al's transcutaneous ultrasonography-secretin for imaging the pancreatic duct. After injection of secretin, the pancreatic duct is imaged every minute for 15 minutes, and ductal dilation greater than 1 mm from baseline is considered abnormal. Of 22 patients with divisum and acute pancreatitis, 14 had a positive EUS-secretin test result, and 8 had a negative test result. Thirteen of 14 patients with a positive test result responded to endoscopic therapy of the minor papilla (93% positive predicted value), whereas 5 of 8 patients with a negative test result did not respond to therapy (62 negative predictive value). The utility of this procedure must be validated by other investigators. TECHNIQUES OF ENDOSCOPIC THERAPY

The goal of endoscopic therapy in patients with symptomatic pancreas divisum is to relieve the proposed stenosis of the minor papilla. The options include dilation and stenting of the minor papilla, minor papilla sphincterotomy, and stenting and alternative techniques. The Milwaukee groupz1advocates catheter dilation and stenting of the minor papilla at 4-month intervals for 1 year. This group performed a small, unblinded, randomized trial comparing dilation and stenting to medical therapy in a group of patients with unexplained ARP and pancreas divisum. Ten patients were randomized to sequential dorsal duct stenting compared with 9 controls (Table 2). Patients in the stent group had no emergency department visits or hospitalizations, only one episode of pancreatitis, and a 90% overall clinical improvement rate. These results were significantly better than those seen in the control group. Four of the 9 controls were crossed over to stent therapy, with subsequent resolution of symptoms. Pancreatic stenting for a 4-month interval has several inherent problems. First, pancreatic duct stents have a high rate of stent occlusion. Fifty percent of pancreatic stents are occluded by 6 weeks, with a linear progression so that all are occluded by 9 weeks after placernent.l6Second, there is a 5% prevalence of stent migration into the pancreatic duct, and, although most stents can be retrieved, not all can.ls Removal of the inner flap of the stent reduces inward migration. Finally, pancreatic stents induce morphologic changes that resemble chronic pancreatitis. The changes include dilation of the main duct and stricture and ectasias of the secondary branches.19Many of these radiographic changes are reversible. There is concern that these changes may lead to chronic parenchymal damage. The trend among endoscopists is to place 1- to 3-cm pancreatic duct

Table 2. RESULTS OF A RANDOMIZED, CONTROLLED TRIAL OF MINOR PAPILLA STENTING IN PANCREAS DlVlSUM AND RECURRENT PANCREATITIS'

Group

Stent Control

Number of Hospital Patients Admissions 10

0

9

5*

' P <0.05 Data from reference 21.

Emergency Room Attacks of Mean Improved (%I Visits Pancreatitis Follow-UD 0 2

1 7*

28

31

9 (90) 1 (lly

PANCREAS DIVISUM

473

Figure 3. Endoscopic stenting of the dorsal duct. A, A dorsal pancreatogram with mild dilation of the duct. B, Placement of a 7 French plastic stent, with drainage of contrast media.

stents for brief periods of time, that is, less than 1 week, to reduce the risk for these complications (Fig. 3) . Most endoscopists advocate minor papilla sphincterotomy (MIES), usually with short-term stenting to prevent or reduce postsphincterotomy pancreatitis. The initial technique of MIES consisted of a needle knife sphincterotomy over a dorsal duct stent.22, 27, 28 The stent provides a good landmark to guide the incision while protecting against perforation. In experienced hands, technical success rates are high after the stent has been placed, with mild to moderate pancreatitis being the most common problem (10?!0-29%). Restenosis of the minor papilla with clinical relapse of symptoms has been reportedz2and may be a function of the size of the initial incision. An alternative technique is wire-guided MIES, in which a standard sphincterotome is inserted over a guidewire.8,15This allows for a more generous sphincterotomy, after which a stent can be placed over the wire (Fig. 4). There are no comparative data. A second alternative endoscopic method is injection of botulinum toxin into the minor papilla. Wehrmann et a131 reported this in five patients with acute pancreatitis with initial resolution of attacks for a mean of 7 months without complications. Three of the four patients who relapsed remained in sustained remission after further treatment. They advocate botulinum toxin as a quick, safe technique and a useful test to predict whether patients will respond to sphincterotomy. When patients have an abnormal pancreatogram, endoscopic therapy should be tailored to the specific finding. Patients with changes of obvious chronic pancreatitis and no obstruction respond less well to endoscopic therapy than patients with treatable casuses of obstruction. Obstructing strictures and stones are addressed endoscopically in the same fashion as for patients with normal pancreatic duct anatomy. Whether some patients with chronic pancreatitis have ductal hypertension in the absence of demonstrable obstruction remains controversial. RESPONSE TO ENDOSCOPIC THERAPY Table 3 lists all reported series of endoscopic sphincterotomy of the minor papilla. The results of therapy must be analyzed separately according to clinical

474

COHEN & SIEGEL

Figure 4. Video endoscopic images demonstrating wire-guided sphincterotomy of the minor papilla. The native minor papilla is seen in the upper left image. The lower images demonstrate sphincterotomy across the duodenal fold, and the guidewire is left in place for stent placement.

classification of patients. Patients with ARP, normal dorsal ducts, and no chronic pain have the best results. Seventy-five percent of these patients have no further attacks and become asymptomatic. Among patients who relapse with subsequent attacks of pancreatitis, most do so within 6 months, and some have restenosis of the minor papilla, that is, a technical failure that may respond to further endoscopic or surgical therapy. Other patients who have patent minor papillae are presumed to have nonanatomic explanations for pancreatitis. In patients with chronic pancreatitis, overall clinical improvement can vary 22 Complication rates also vary from 3% to 30%? 22 mostly from 27% to consisting of mild pancreatitis. Patients with an identifiable obstruction (i.e., stricture, papillary stenosis, or stones) close to the duodenum are most likely to benefit (e.g., relief of pain or reduction in attacks of pancreatitis) if that obstruction is successfully treated endoscopically. The results of endoscopic therapy are most controversial in the subgroup of patients with chronic abdominal pain of pancreatic origin but without any objective evidence of pancreatitis. Clinical improvement in pain varies from 20% to 50% after endoscopic treatment (see Table 3).7,9, 22, 25 Although some groups report high complication rates (5SOYO), others report lower rates (15%-30%).7*9*22 In a controlled trial of endoscopic therapy versus medical management, the Indiana groupz5found a trend toward clinical improvement in favor of endoscopic therapy (44% vs. 24%), with the only significant complication being a

1990 1991 1993 1993 1994 1995 1995

31 24 35 51 16 18 39

(n)

‘Acute recurrent pancreatitis

Year

Study

SiegelZ7 GreggI5 Coleman9 Lehmanzz Shermanz Cohen’ Kozarekzo

~

26/31 21/24 21/35 22/51 7/16 9/18 18/39

Improved

Total Patients

(%)

88 60 43 43.8 50 46

84

~~

3/7 11/15

10/13 13/17

-

-

-

43 73

77 76

No. Improved (n) (%)

ARP*

1/5 6/23 7/16 6/11 1/5

20 26 43.8 55 20

No. improved (n) (%)

Pain Only

6/19

10/17 3/11

-

-

-

-

32

59 27

10/35 2/51

-

-

-

28.5 4

Major Comp (n) (%)

Chronic Pancreatitis No. improved (n) (%)

Table 3. RESULTS OF SERIES OF ENDOSCOPIC THERAPY IN PATIENTS WITH PANCREAS DlVlSUM

24 23 20 24 24 20

Mean Follow-Up (months)

476

COHEN & SIEGEL

13%prevalence of pancreatitis. This is similar to the authors' clinical experience. Patients with a n abdominal pain syndrome must be selected carefully before endoscopic therapy to exclude patients with psychosocial dysfunction a n d irritable bowel syndrome. A frank discussion about the risks and severity of potential complications is mandatory. Incomplete divisum exists when a small, threadlike connection exists between the ventral and dorsal ducts b u t most pancreatic secretions still flow through the minor papilla (Fig. 1D). Warshaw et a130 named this the dominant dorsal duct syndrome. In one endoscopic series,"j dilation and stenting were used in 18 patients with incomplete divisum; 60% of patients with ARP and 80% of patients with chronic pancreatitis benefitted from endoscopic therapy. One of 3 patients with pain only improved, however. This indicates that the results for incomplete divisum are similar to those for classic divisum. SUMMARY Pancreas divisum is a common congenital variation that can be associated with pancreatic disease. Symptomatic patients with divisum must b e classified according to clinical presentation a n d morphologic findings. Response to endoscopic therapy is best in patients with ARP, of whom 75% benefit. Results in patients with chronic pancreatitis and pain but without objective pancreatitis are mixed, and patients should be carefully selected.

References 1. Benage D, McHenry R, Hawes RH, et a1 Minor papilla cannulation and dorsal

ductography in pancreas divisum. Gastrointest Endosc 36:553, 1990 2. Bernard JP, Sahel J, Giovanni M, et al: Pancreas divisum is a probable cause of acute pancreatitis: A report of 137 cases. Pancreas 5:248, 1990 3. Blair AJ, Russell CG, Cotton PB: Resection for pancreatitis in patients with pancreas divisum. Ann Surg 200:590, 1984 4. Burtin P, Person B, Chameau J, et a1 Pancreas divisum and pancreatitis: a coincidental association? Endoscopy 23:55, 1991 5. Catalan0 MF, Lahoti S, Alcocer E, et a1 Dynamic imaging of the pancreas using real-time endoscopic ultrasonography with secretin stimulation. Gastrointest Endosc 48:580, 1998 6. Carr-Locke DL: Pancreas divisum: the controversy goes on? Endoscopy 23:88, 1991 7. Cohen SA, Rutkovsky FD, Siegel JH, et a1 Endoscopic stenting and sphincterotomy of the minor papilla in symptomatic pancreas divisum: Results and complications. Diagnostic and Therapeutic Endoscopy 1:131, 1995 8. Cohen SA, Kasmin FE, Siegel JH: Wire-guided sphincterotomy of the minor pappila in pancreas divisum. Am J Gastroenterol 90:1601, 1995 9. Coleman SD, Cotton PB: Endoscopic accessory sphincterotomy and stenting in pancreas divisum. Gastrointest Endosc 39:312, 1993 10. Cotton PB, Kizu M: Malfusion of dorsal and ventral pancreas: A cause of pancreatitis? [Abstract]. Gut 18:400, 1977 11. Cotton PB: Congenital anomaly of pancreas divisum as a cause of obstructive pain and pancreatitis. Gut 21:105, 1980 12. Cotton PB: Pancreas divisum: curiosity or culprit? Gastroenterology 89:1431, 1985 13. Delhaye M, Engelholm L, Cremer M: Pancreas divisum: Congenital anatomic variant or anomaly? Gastroenterology 89:951, 1985 14. Gregg JA: Pancreas divisum: Its association with pancreatitis. Am J Surg 134:539, 1977 15. Gregg JA, OConnor PJ, Sten J S Treatment of pancreas divisum by endoscopic sphinc-

PANCREAS DIVISUM

16. 17.

18. 19. 20.

21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.

477

terotomy and/or hydrostatic balloon dilation of the dorsal pancreatic duct sphincter. Am J Gastroenterol 861329, 1991 Ikenberry SO, Sherman S, Hawes R, et al: The occlusion rate of pancreatic stents. Gastrointest Endosc 40:611, 1994 Jacobs L, Geenen JE, Catalan0 MF, et al: Clinical presentation and short-term outcome of endoscopic therapy of patients with symptomatic incomplete pancreas divisum. Gastrointest Endosc 49:53, 1999 Johanson JF, Schmalz MJ, Geenen JE: Incidence and risk factors for biliary and pancreatic stent migration. Gastrointest Endosc 38:341, 1992 Kozarek RA: Pancreatic stents induced ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 3693, 1990 Kozarek RA, Ball TJ, Paterson DJ, et al: Endoscopic approach to pancreas divisum. Dig Dis Sci 40:1974, 1995 Lans JI, Geenen JE, Johanson JF, et al: Endoscopic therapy in patients with pancreas divisum in acute pancreatitis: A prospective, randomized, controlled clinical trial. Gastrointest Endosc 38:430, 1992 Lehman GA, Sherman S, Nisi R, et al: Pancreas divisum: Results of minor papilla sphincterotomy. Gastrointest Endosc 39:1, 1993 Satterfield ST, McCarthy JH, Geenen JE, et al: Clinical experience in 82 patients with pancreas divisum: Preliminary results of manometry and endoscopic therapy. Pancreas 3248, 1988 Staritz M, Meyer vun Buschenfelde KH: Elevated pressure in the dorsal part of pancreas divisum: cause of chronic pancreatitis? Pancreas 3:108, 1988 Sherman S, Hawes R, Nisi R, et al: Randomized controlled trial of minor papilla sphincterotomy in pancreas divisum patients with pain only. Gastrointest Endosc 40:P125, 1994 Siegel JH, Yatto RP, Vender RJ: Anomalous pancreatic ducts causing "pseudomass" of the pancreas. J Clin Gastroenterol 5:33, 1983 Siegel JH, Ben-Zvi JS, Pullano W, et al: Effectiveness of endoscopic drainage for pancreas divisum: Endoscopic and surgical results in 31 patients. Endoscopy 22329, 1990 Siegel JH: Endoscopic Retrograde Cholangiopancreatography: Technique, Diagnosis, and Therapy. New York, Raven, 1992 Sugawa C, Walt AJ, Nunez DC, et al: Pancreas divisum: Is it a normal anatomic variant? Am J Surg 153:62, 1987 Warshaw AL, Sineone JF, Shapiro RH, et al: Evaluation and treatment of the dominant dorsal duct syndrome. Am J Surg 159:59, 1990 Wehrmann T, Schmitt T, Seifert H: Endoscopic botulinum toxin injection into the minor papilla for treatment of idiopathic recurrent pancreatitis in patients with pancreas divisum. Gastrointest Endosc 50:545, 1999

Address reprint requests to Jerome H. Siegel, MD 60 East End Avenue New York, NY 10028