0016-5107/92/3804-0430$03.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1992 by the American Society for Gastrointestinal Endoscopy
Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial J. I. Lans, MD, J. E. Geenen, MD J. F. Johanson, MD, W. J. Hogan, MD Racine, Wisconsin and Milwaukee, Wisconsin
Endoscopic endoprosthesis (stent) placement across the minor papilla has been shown to be beneficial in reducing abdominal pain and episodes of pancreatitis in a small group of patients with pancreas divisum and acute recurrent pancreatitis. In a randomized, controlled clinical trial, 19 patients with pancreas divisum and at least 2 documented episodes of pancreatitis were randomized to either dorsal duct stent placement (10 patients-5 women and 5 men) or controls (9 patients6 women and 3 men). All other causes of pancreatitis were excluded. Patients were followed at 4·month intervals for evaluation and/or stent exchange during a 1-year period. The following criteria were evaluated during follow-up: number of hospitalizations or emergency room visits, the number of documented episodes of pancreatitis, and gradation of the patient's overall general feeling based on a visual analog scale. Mean follow-up times in the stent and control groups were 28.6 and 31.5 months, respectively (p > 0.05, NS). No patients in the stent group required hospitalization or emergency room visits for abdominal pain only during and following the treatment period. However, in the control group there were five hospitalizations and two emergency room visits for abdominal pain during a similar period (p < 0.05). Pancreatitis was documented with an elevated amylase twice the normal range, one time in the stent group and seven times in the control group (p < 0.05). Based on visual analog scale determinations, 9 of 10 (90%) patients in the stent group reported ;::50% symptomatic improvement compared with 1 of 9 (11%) patients in the control group (p < 0.05). Four of nine patients in the control group did poorly and subsequently had stent placement. These patients did not require hospitalization or suffer any further episodes of pancreatitis for a period ranging from 6 to 53 months. Dorsal pancreatic duct stent placement across the minor papilla in patients with pancreas divisum and acute recurrent pancreatitis resulted in significant objective and subjective clinical improvement compared with controls in a short-term follow-up study. (Gastrointest Endosc 1992;38:430-434)
Pancreas divisum is a congenital anomaly caused by failure of fusion of the ventral and dorsal pancreatic anlagen during the sixth and seventh week of gestation. When this occurs, the major portion of the panReceived November 14, 1991. For revision January 7, 1992. Accepted April 13, 1992. From the Digestive Disease Center, St. Luke's Hospital, Racine, Wisconsin and Department of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin. Reprint requests: Joseph E. Geenen, MD, 1333 College Avenue, Racine, Wisconsin 53403. 430
creas drains through the minor papilla via the duct of Santorini and the ventral duct, or duct of Wirsung, drains only the small ventral pancreas. Based on a large autopsy series, it is estimated that 5 to 10% of the population has pancreas divisum. 1 The definitive diagnosis of pancreas divisum is made by ERCP or operative pancreatography. There is a controversy as to whether pancreas divisum is associated with an increased incidence of recurrent attacks of pancreatitis. This association has been GASTROINTESTINAL ENDOSCOPY
championed by Cotton,2 Richter et al} and Gregg,4 but refuted by Delhaye et al. 5 The proposed mechanism for acute recurrent pancreatitis in patients with pancreas divisum is relative obstruction to the flow of pancreatic secretion caused by the tiny minor papilla which leads to pancreatitis. There are a variety of treatment programs that have been used in the management of pancreas divisum and acute recurrent pancreatitis. The major thrust of all of these has been to improve drainage of the minor duct. Endoscopic and surgical treatment have both achieved some measure of success. 3 - 12 Although each type of therapy for pancreas divisum and acute recurrent pancreatitis has its proponents, there is no modality that has been accepted as standard treatment for this condition. Controlled clinical trials comparing different treatment modalities have not been reported. We wish to report our experience with endoscopic therapy in patients with pancreas divisum and acute recurrent pancreatitis in a prospective, randomized, controlled clinical trial.
could not be fully inserted into the pancreatic duct, the patient was excluded from the study. Our success rate in accomplishing the above was 83%. Diazepam or midazolam in conjunction with meperidine were administered intravenously for conscious sedation. After ERCP demonstrated pancreas divisum, an 0.018inch guidewire was advanced to the tail of the dorsal pancreatic duct. The patient was then randomized by card selection to one of two study groups: dorsal pancreatic duct stent placement or a control group in whom no treatment was performed (Figs. 1 and 2). Ten patients were randomly assigned to dorsal pancreatic duct stent placement and nine patients were randomized to the control group. The stent group included five men and five women (mean age, 49.7 years; range, 20 to 79 years) and the control group included three men and six women (mean age, 46.4 years; range, 29 to 72 years) (p > 0.05, NS). Each patient was informed whether or not a stent was placed across the minor papilla because of the necessity of repeat ERCP and stent placement. In the stent group the minor papilla was serially
PATIENTS AND METHODS
All patients seen at St. Luke's Hospital, Racine, Wisconsin, from 1985 to 1990 with pancreas divisum and acute recurrent pancreatitis were entered into the clinical trial. A total of 19 patients were studied. The diagnosis of pancreas divisum was established by pancreatogram. Acute recurrent pancreatitis was defined as two or more episodes of abdominal pain with associated serum amylase elevations twice the range of normal. All patients were evaluated for identifiable causes of pancreatitis such as alcohol, gallstones, trauma, medication related, hypertriglyceridemia, hypercalcemia, and family history. All patients with a possible cause of acute recurrent pancreatitis were excluded. Chronic pancreatitis was excluded by a negative pancreatic ultrasound and CT scan, diagnostic ERCP, and/or a pancreatic duodenal or intraductal secretin test. 13 Patients who had prior pancreatic resection or pancreatic sphincteroplasty were also excluded from the study. At initial evaluation, a comprehensive health questionnaire regarding the patient's symptomatology, current medications, past hospitalizations and operations, and social history was completed. Previous radiographs and laboratory studies were reviewed. The patient was also asked to "grade" pain symptomatology based on a visual analog scale (0, no pain; 10, worst pain) at the initial and subsequent visits. At each visit patients were questioned regarding the use of narcotic analgesics and emergency room visits, hospitalizations, or physician office visits related to their recurrent pancreatitis or abdominal pain. Following informed written consent, each patient had a diagnostic ERCP. The major papilla was identified, cannulated, and the common bile duct and the ventral pancreatic duct were satisfactorily outlined by radiopaque contrast. Subsequently, the accessory papilla was localized and cannulated with a fine, tapered needle-tip catheter or angiocatheter (3 F) inserted over a 0.018-inch guidewire. If the minor papilla could not be freely cannulated or if a guidewire VOLUME 38, NO.4, 1992
Figure 1. This radiograph reveals a ventral duct pancreatogram obtained by cannulation of the major papilla and a dorsal duct pancreatogram obtained by cannulation of the minor papilla.
Figure 2. A O.018-inch guidewire has been advanced through the minor papilla to the tail of the dorsal pancreatic duct.
431
dilated with a graduated 4 to 7 F Soehendra catheter. Following this a 5 or 7 F pancreatic stent of variable length was passed over the guidewire and positioned in the dorsal pancreatic duct so that it bridged the minor papilla (Figs. 3 and 4). The stent length was varied between 3 and 7 cm to avoid repetitious contact to the pancreatic duct by the tip of the stent. The patients were followed at 4-month intervals for 1 year. The patients' symptoms were evaluated and each patient underwent a repeat ERCP if clinically warranted. In the stent group the prosthesis was replaced utilizing a stent of different length. At the end of the first year, the stent was removed. In the control group, patients were followed up every 4 months. If the patient had an episode of recurrent pancreatitis during this time, ERCP was repeated. Otherwise, if they were doing well, the clinical course was reviewed during a telephone interview. The effectiveness of treatment was documented using the questionnaire method during each visit or telephone conversation. The following criteria were evaluated: (1) number of hospitalizations and emergency room visits for abdominal
Figure 3. This illustration shows a stent positioned across the minor papilla in the dorsal pancreatic duct. The ventral pancreatic duct which drains via the major papilla is shown inferiorly.
pain only, (2) number of documented episodes of acute pancreatitis, and (3) patients' overall general feeling was graded on the visual analog scale. Statistical analysis was performed using a non-paired Student's t test and analysis of variance. The Institutional Review Board of St. Luke's Hospital approved this clinical trial in 1985.
RESULTS
Nineteen patients with a diagnosis of pancreas divisum and acute recurrent pancreatitis were entered into the study over a consecutive 5-year period. Each patient had at least two documented episodes of acute pancreatitis and the pancreatograms of all patients were consistent with complete (non-communicating) pancreas divisum. No alterations of the dorsal duct or lateral branches were noted. Thirteen of the 19 patients had either a conventional secretin test or an abbreviated intraductal secretin test. 13 All secretin test results were within normal range. The stent diameter in the treatment group was 5 or 7 F; length was variable. All stents had dual side barbs located at each end. Two patients in the stent group had dorsal duct stent migration into the pancreatic duct during the study. These stents were removed endoscopically and replaced with larger diameter stents. One patient had migration of the stent into the duodenum and pancreatic duct stent replacement was accomplished subsequently. There were no inflammatory strictures of the dorsal duct noted during or following stent therapy. After the 1 year of stent therapy, the prosthesis was permanently removed and these patients were followed in a similar fashion to the control group. Mean follow-up period for the stent group was 28.6 months; for the control group it was 31.5 months (p > 0.05, NS). In the stent treatment group, no patients required hospitalization or emergency room visits for abdominal pain only, during or following stent therapy. In the control group, five patients required hospitalization and two patients visited the emergency room during a similar period (p < 0.05) (Fig. 5). One patient developed a documented episode of pancreatitis immediately prior to replacement of an occluded stent. This attack was less severe in nature compared with episodes experienced prior to stent therapy. Seven documented attacks of pancreatitis were documented in six patients in the control group during the study and follow-up period (p < 0.05) (Fig. 6).
Figure 4. Endoscopic photograph showing a 5 F endoprosthesis that has been placed across the minor papilla (small arrow). Immediately below the stent is the major papilla (broad arrow). 432
The patient questionnaires attempted to evaluate the patients' symptoms and overall general physical well-being during the study and follow-up period based on a visual analog scale. Nine patients in the stent therapy group rated their improvement ~50% during this study; only one patient in the control group scored improvement ~50% (p < 0.05) (Fig. 7). GASTROINTESTINAL ENDOSCOPY
0
7 •
9
9 8
7 6
I
I
*
r
)
Control Group
Patient Group
< 0.05
• r < 0.0,
Figure 5. Comparison of frequency of hospitalizations and emergency room (ER) visits for abdominal pain without amylase elevation during and after therapy in the control group and the stent group.
•
~ Control Group
Stem Group
Figure 7. Overall subjective improvement in pancreas divisum
patients with pancreatitis (based on a visual analog scale) in the control patients and the stent group during and after therapy. One of nine patients in the control group had overall subjective improvement compared with 9 of 10 patients in the stent group.
7 •
• r < lUI,
('(mln)1 Group
Figure 6. Comparison of the total number of documented attacks of pancreatitis during and after therapy in the control group and the stent group.
Four patients in the control group who did quite poorly after the study period with episodes of acute recurrent pancreatitis or abdominal pain subsequently had dorsal duct stent placement. One patient has been followed up for an additional 53 months and another patient for 23 months after stent removal. Neither patient has required hospitalization or experienced any further episodes of pancreatitis. The two other patients have had pancreatic duct stent placement only for 6 months, but they are, likewise, asymptomatic. DISCUSSION
The etiology of pancreatitis in patients with pancreas divisum is unknown. It is speculated that it VOLUME 38, NO. 4, 1992
could be due to a structural abnormality of the minor papilla which compromises the outflow of pancreatic juice into the duodenum or causes precipitation of proteinaceous plugs within the pancreatic duct eventually blocking flow of pancreatic secretion. 14 Several treatment modalities have been advocated for patients with acute recurrent pancreatitis and pancreas divisum. Operative sphincteroplasty of the minor papilla or dual sphincteroplasty (major and minor papilla) are the two most frequently employed surgical procedures. 3, 6, 12 After surgery, post-operative stenosis of the minor papilla may occur, and in several reported cases severe chronic pancreatitis has developed.? Endoscopic sphincterotomy of the minor papilla is another therapeutic option, but there is an increased risk of severe pancreatitis, and restenosis has occurred. 9 , 10 In two separate clinical trials involving endoscopic stent placement into the dorsal pancreatic duct across the minor papilla, we have reported improvement in patients' abdominal pain and a decrease in the frequency of acute recurrent pancreatitiS. B,l1 We have shown in this randomized, controlled, clinical study that the endoscopic placement of a stent into the dorsal pancreatic duct across the minor papilla in patients with acute recurrent pancreatitis and pancreas divisum results in a statistically significant decrease in the incidence of pancreatitis and abdominal pain during short-term follow-up. There is also a marked subjective improvement in those patients who were treated with a pancreatic duct stent. To further substantiate the effectiveness of stent therapy, four control group patients who did poorly in terms of 433
continued abdominal pain and recurrent episodes of pancreatitis subsequently had stent placement into their dorsal pancreatic duct. These patients have done extremely well and have not experienced any further attacks of pancreatitis. In a prospective clinical trial, improvement following endoscopic stent placement across the minor papilla in patients with acute recurrent pancreatitis and pancreas divisum suggested that relief may be obtained from subsequent definitive surgical sphincteroplasty. Those patients that did well endoscopically did well following operation. I5 Several disadvantages following pancreatic stent placement have been reported, including structural alterations in the pancreatic duct simulating those observed with chronic pancreatitis and overt ductal strictures. I6 Additionally the stent may migrate into or out of the pancreatic duct. Inward migration may require operative intervention to remove the foreign body. We have reported that pancreatic ductal changes occur in the majority of patients undergoing endoscopic stent therapy, but these alterations are for the most part reversible following stent removal. However, pancreatic duct stenting has been associated with a 7% rate of ductal stricturing and these patients may progress to chronic pancreatitis. I? In this study, the length of the stent was varied with each stent exchange. No episodes of pancreatic ductal stricturing were observed. The prolonged exposure of anyone portion of the pancreatic duct to the end of the endoprosthesis may cause pancreatic duct stricturing. Altering the length of the stent at short intervals can, therefore, possibly prevent this localized complication. In a recent study, our group has shown that modification of pancreatic duct stent by removal of the two inner barbs also reduces the rate of intraductal migration of the stents. I8 We have demonstrated that dorsal pancreatic duct stent therapy in patients with acute recurrent pancreatitis and pancreas divisum results in significant objective and subjective improvement in short-term follow-up. The long-term implications of endoprosthesis treatment are unknown; stenting may result in dilation of the minor papillary sphincter. The results of this study suggest that impairment of pancreatic
434
drainage by the minor papilla may be an etiology for recurrent pancreatitis in patients with pancreas divisum.
REFERENCES 1. Dawson W, Langman J. An anatomic radiologic study on pancreatic duct pattern in man. Anat Rec 1961;39:59-68. 2. Cotton PB. Congenital anomaly of pancreas divisum as a cause of obstructive pain and pancreatitis. Gut 1980;21:105-14. 3. Richter JM, Schapiro RH, Mulley AC, et al. Association of pancreas divisum and pancreatitis and its treatment by sphincteroplasty of the accessory ampulla. Gastroenterology 1981;81:1104-10. 4. Gregg JA. Pancreas divisum: its association with pancreatitis. Am J Surg 1977;134:539-43. 5. Delhaye M, Engelholm L, Cremer M. Pancreas divisum: congenital anatomic variant or anomaly. Contribution of endoscopic retrograde dorsal pancreatography. Gastroenterology 1985;89:951-8. 6. Britt L, Samuels A. Pancreas divisum: is it a surgical disease? Ann Surg 1983;197:654-61. 7. Carey L. Pancreas divisum. American Gastroenterological Association Postgraduate Course, May 1985, p 83. 8. Satterfield ST, McCarthy JH, Geenen JE, et al. Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy. Pancreas 1988;3:24853. 9. Russell CG, Wong W, Cotton PH. Accessory sphincterotomy (endoscopic and surgical) in patients with pancreas divisum. Br J Surg 1984;71:954-7. 10. Lehman G, O'Connor K, Troiano F, Benage D. Endoscopic papillotomy and stenting of the minor papilla in pancreas divisum [Abstract). Gastrointest Endosc 1989;35:167. 11. Prabhu M, Geenen JE, Hogan WJ, et al. Role of endoscopic stent placement in the treatment of acute recurrent pancreatitis associated with pancreas divisum: a prospective assessment [Abstract). Gastrointest Endosc 1989;35:165. 12. Warshaw AL. Pancreas divisum: a case for surgical treatment. Adv Surg 1988;21:93. 13. Gregg JA. The intraductal secretin test (IDST). An adjunct to the diagnosis of pancreatic disease and pancreatic physiology. In: Sivak M, ed. Gastroenterologic endoscopy. Philadelphia: WB Saunders, 1987:794-807. 14. Geenen JE. A/S/G/E distinguished lecture-endoscopic therapy of pancreatic disease: a new horizon. Gastrointest Endosc 1988;34:386-9. 15. Siegel JH, Ben-Zvi JS, Pullano W, Cooperman A. Effectiveness of endoscopic drainage for pancreas divisum: endoscopic and surgical results in 31 patients. Endoscopy 1990;22:129-33. 16. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 1990;36:93. 17. Derfus GA, Geenen JE, Hogan WJ. Alterations in pancreatic duct morphology associated with endoscopic stent placement [Abstract). Pancreas 1989;5:613. 18. Johanson JF, Schmalz MJ, Geenen JE. Migration of pancreatic duct stents prevented by a simple modification [Abstract). Gastrointest Endosc 1991;37:272.
GASTROINTESTINAL ENDOSCOPY
Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial J. I. Lans, MD, J. E. Geenen, MD J. F. Johanson, MD, W. J. Hogan, MD Racine, Wisconsin and Milwaukee, Wisconsin
Endoscopic endoprosthesis (stent) placement across the minor papilla has been shown to be beneficial in reducing abdominal pain and episodes of pancreatitis in a small group of patients with pancreas divisum and acute recurrent pancreatitis. In a randomized, controlled clinical trial, 19 patients with pancreas divisum and at least 2 documented episodes of pancreatitis were randomized to either dorsal duct stent placement (10 patients-5 women and 5 men) or controls (9 patients6 women and 3 men). All other causes of pancreatitis were excluded. Patients were followed at 4·month intervals for evaluation and/or stent exchange during a 1-year period. The following criteria were evaluated during follow-up: number of hospitalizations or emergency room visits, the number of documented episodes of pancreatitis, and gradation of the patient's overall general feeling based on a visual analog scale. Mean follow-up times in the stent and control groups were 28.6 and 31.5 months, respectively (p > 0.05, NS). No patients in the stent group required hospitalization or emergency room visits for abdominal pain only during and following the treatment period. However, in the control group there were five hospitalizations and two emergency room visits for abdominal pain during a similar period (p < 0.05). Pancreatitis was documented with an elevated amylase twice the normal range, one time in the stent group and seven times in the control group (p < 0.05). Based on visual analog scale determinations, 9 of 10 (90%) patients in the stent group reported ;::50% symptomatic improvement compared with 1 of 9 (11%) patients in the control group (p < 0.05). Four of nine patients in the control group did poorly and subsequently had stent placement. These patients did not require hospitalization or suffer any further episodes of pancreatitis for a period ranging from 6 to 53 months. Dorsal pancreatic duct stent placement across the minor papilla in patients with pancreas divisum and acute recurrent pancreatitis resulted in significant objective and subjective clinical improvement compared with controls in a short-term follow-up study. (Gastrointest Endosc 1992;38:430-434)
Pancreas divisum is a congenital anomaly caused by failure of fusion of the ventral and dorsal pancreatic anlagen during the sixth and seventh week of gestation. When this occurs, the major portion of the panReceived November 14, 1991. For revision January 7, 1992. Accepted April 13, 1992. From the Digestive Disease Center, St. Luke's Hospital, Racine, Wisconsin and Department of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin. Reprint requests: Joseph E. Geenen, MD, 1333 College Avenue, Racine, Wisconsin 53403. 430
creas drains through the minor papilla via the duct of Santorini and the ventral duct, or duct of Wirsung, drains only the small ventral pancreas. Based on a large autopsy series, it is estimated that 5 to 10% of the population has pancreas divisum. 1 The definitive diagnosis of pancreas divisum is made by ERCP or operative pancreatography. There is a controversy as to whether pancreas divisum is associated with an increased incidence of recurrent attacks of pancreatitis. This association has been GASTROINTESTINAL ENDOSCOPY
championed by Cotton,2 Richter et al} and Gregg,4 but refuted by Delhaye et al. 5 The proposed mechanism for acute recurrent pancreatitis in patients with pancreas divisum is relative obstruction to the flow of pancreatic secretion caused by the tiny minor papilla which leads to pancreatitis. There are a variety of treatment programs that have been used in the management of pancreas divisum and acute recurrent pancreatitis. The major thrust of all of these has been to improve drainage of the minor duct. Endoscopic and surgical treatment have both achieved some measure of success. 3 - 12 Although each type of therapy for pancreas divisum and acute recurrent pancreatitis has its proponents, there is no modality that has been accepted as standard treatment for this condition. Controlled clinical trials comparing different treatment modalities have not been reported. We wish to report our experience with endoscopic therapy in patients with pancreas divisum and acute recurrent pancreatitis in a prospective, randomized, controlled clinical trial.
could not be fully inserted into the pancreatic duct, the patient was excluded from the study. Our success rate in accomplishing the above was 83%. Diazepam or midazolam in conjunction with meperidine were administered intravenously for conscious sedation. After ERCP demonstrated pancreas divisum, an 0.018inch guidewire was advanced to the tail of the dorsal pancreatic duct. The patient was then randomized by card selection to one of two study groups: dorsal pancreatic duct stent placement or a control group in whom no treatment was performed (Figs. 1 and 2). Ten patients were randomly assigned to dorsal pancreatic duct stent placement and nine patients were randomized to the control group. The stent group included five men and five women (mean age, 49.7 years; range, 20 to 79 years) and the control group included three men and six women (mean age, 46.4 years; range, 29 to 72 years) (p > 0.05, NS). Each patient was informed whether or not a stent was placed across the minor papilla because of the necessity of repeat ERCP and stent placement. In the stent group the minor papilla was serially
PATIENTS AND METHODS
All patients seen at St. Luke's Hospital, Racine, Wisconsin, from 1985 to 1990 with pancreas divisum and acute recurrent pancreatitis were entered into the clinical trial. A total of 19 patients were studied. The diagnosis of pancreas divisum was established by pancreatogram. Acute recurrent pancreatitis was defined as two or more episodes of abdominal pain with associated serum amylase elevations twice the range of normal. All patients were evaluated for identifiable causes of pancreatitis such as alcohol, gallstones, trauma, medication related, hypertriglyceridemia, hypercalcemia, and family history. All patients with a possible cause of acute recurrent pancreatitis were excluded. Chronic pancreatitis was excluded by a negative pancreatic ultrasound and CT scan, diagnostic ERCP, and/or a pancreatic duodenal or intraductal secretin test. 13 Patients who had prior pancreatic resection or pancreatic sphincteroplasty were also excluded from the study. At initial evaluation, a comprehensive health questionnaire regarding the patient's symptomatology, current medications, past hospitalizations and operations, and social history was completed. Previous radiographs and laboratory studies were reviewed. The patient was also asked to "grade" pain symptomatology based on a visual analog scale (0, no pain; 10, worst pain) at the initial and subsequent visits. At each visit patients were questioned regarding the use of narcotic analgesics and emergency room visits, hospitalizations, or physician office visits related to their recurrent pancreatitis or abdominal pain. Following informed written consent, each patient had a diagnostic ERCP. The major papilla was identified, cannulated, and the common bile duct and the ventral pancreatic duct were satisfactorily outlined by radiopaque contrast. Subsequently, the accessory papilla was localized and cannulated with a fine, tapered needle-tip catheter or angiocatheter (3 F) inserted over a 0.018-inch guidewire. If the minor papilla could not be freely cannulated or if a guidewire VOLUME 38, NO.4, 1992
Figure 1. This radiograph reveals a ventral duct pancreatogram obtained by cannulation of the major papilla and a dorsal duct pancreatogram obtained by cannulation of the minor papilla.
Figure 2. A O.018-inch guidewire has been advanced through the minor papilla to the tail of the dorsal pancreatic duct.
431
dilated with a graduated 4 to 7 F Soehendra catheter. Following this a 5 or 7 F pancreatic stent of variable length was passed over the guidewire and positioned in the dorsal pancreatic duct so that it bridged the minor papilla (Figs. 3 and 4). The stent length was varied between 3 and 7 cm to avoid repetitious contact to the pancreatic duct by the tip of the stent. The patients were followed at 4-month intervals for 1 year. The patients' symptoms were evaluated and each patient underwent a repeat ERCP if clinically warranted. In the stent group the prosthesis was replaced utilizing a stent of different length. At the end of the first year, the stent was removed. In the control group, patients were followed up every 4 months. If the patient had an episode of recurrent pancreatitis during this time, ERCP was repeated. Otherwise, if they were doing well, the clinical course was reviewed during a telephone interview. The effectiveness of treatment was documented using the questionnaire method during each visit or telephone conversation. The following criteria were evaluated: (1) number of hospitalizations and emergency room visits for abdominal
Figure 3. This illustration shows a stent positioned across the minor papilla in the dorsal pancreatic duct. The ventral pancreatic duct which drains via the major papilla is shown inferiorly.
pain only, (2) number of documented episodes of acute pancreatitis, and (3) patients' overall general feeling was graded on the visual analog scale. Statistical analysis was performed using a non-paired Student's t test and analysis of variance. The Institutional Review Board of St. Luke's Hospital approved this clinical trial in 1985.
RESULTS
Nineteen patients with a diagnosis of pancreas divisum and acute recurrent pancreatitis were entered into the study over a consecutive 5-year period. Each patient had at least two documented episodes of acute pancreatitis and the pancreatograms of all patients were consistent with complete (non-communicating) pancreas divisum. No alterations of the dorsal duct or lateral branches were noted. Thirteen of the 19 patients had either a conventional secretin test or an abbreviated intraductal secretin test. 13 All secretin test results were within normal range. The stent diameter in the treatment group was 5 or 7 F; length was variable. All stents had dual side barbs located at each end. Two patients in the stent group had dorsal duct stent migration into the pancreatic duct during the study. These stents were removed endoscopically and replaced with larger diameter stents. One patient had migration of the stent into the duodenum and pancreatic duct stent replacement was accomplished subsequently. There were no inflammatory strictures of the dorsal duct noted during or following stent therapy. After the 1 year of stent therapy, the prosthesis was permanently removed and these patients were followed in a similar fashion to the control group. Mean follow-up period for the stent group was 28.6 months; for the control group it was 31.5 months (p > 0.05, NS). In the stent treatment group, no patients required hospitalization or emergency room visits for abdominal pain only, during or following stent therapy. In the control group, five patients required hospitalization and two patients visited the emergency room during a similar period (p < 0.05) (Fig. 5). One patient developed a documented episode of pancreatitis immediately prior to replacement of an occluded stent. This attack was less severe in nature compared with episodes experienced prior to stent therapy. Seven documented attacks of pancreatitis were documented in six patients in the control group during the study and follow-up period (p < 0.05) (Fig. 6).
Figure 4. Endoscopic photograph showing a 5 F endoprosthesis that has been placed across the minor papilla (small arrow). Immediately below the stent is the major papilla (broad arrow). 432
The patient questionnaires attempted to evaluate the patients' symptoms and overall general physical well-being during the study and follow-up period based on a visual analog scale. Nine patients in the stent therapy group rated their improvement ~50% during this study; only one patient in the control group scored improvement ~50% (p < 0.05) (Fig. 7). GASTROINTESTINAL ENDOSCOPY
0
7 •
9
9 8
7 6
I
I
*
r
)
Control Group
Patient Group
< 0.05
• r < 0.0,
Figure 5. Comparison of frequency of hospitalizations and emergency room (ER) visits for abdominal pain without amylase elevation during and after therapy in the control group and the stent group.
•
~ Control Group
Stem Group
Figure 7. Overall subjective improvement in pancreas divisum
patients with pancreatitis (based on a visual analog scale) in the control patients and the stent group during and after therapy. One of nine patients in the control group had overall subjective improvement compared with 9 of 10 patients in the stent group.
7 •
• r < lUI,
('(mln)1 Group
Figure 6. Comparison of the total number of documented attacks of pancreatitis during and after therapy in the control group and the stent group.
Four patients in the control group who did quite poorly after the study period with episodes of acute recurrent pancreatitis or abdominal pain subsequently had dorsal duct stent placement. One patient has been followed up for an additional 53 months and another patient for 23 months after stent removal. Neither patient has required hospitalization or experienced any further episodes of pancreatitis. The two other patients have had pancreatic duct stent placement only for 6 months, but they are, likewise, asymptomatic. DISCUSSION
The etiology of pancreatitis in patients with pancreas divisum is unknown. It is speculated that it VOLUME 38, NO. 4, 1992
could be due to a structural abnormality of the minor papilla which compromises the outflow of pancreatic juice into the duodenum or causes precipitation of proteinaceous plugs within the pancreatic duct eventually blocking flow of pancreatic secretion. 14 Several treatment modalities have been advocated for patients with acute recurrent pancreatitis and pancreas divisum. Operative sphincteroplasty of the minor papilla or dual sphincteroplasty (major and minor papilla) are the two most frequently employed surgical procedures. 3, 6, 12 After surgery, post-operative stenosis of the minor papilla may occur, and in several reported cases severe chronic pancreatitis has developed.? Endoscopic sphincterotomy of the minor papilla is another therapeutic option, but there is an increased risk of severe pancreatitis, and restenosis has occurred. 9 , 10 In two separate clinical trials involving endoscopic stent placement into the dorsal pancreatic duct across the minor papilla, we have reported improvement in patients' abdominal pain and a decrease in the frequency of acute recurrent pancreatitiS. B,l1 We have shown in this randomized, controlled, clinical study that the endoscopic placement of a stent into the dorsal pancreatic duct across the minor papilla in patients with acute recurrent pancreatitis and pancreas divisum results in a statistically significant decrease in the incidence of pancreatitis and abdominal pain during short-term follow-up. There is also a marked subjective improvement in those patients who were treated with a pancreatic duct stent. To further substantiate the effectiveness of stent therapy, four control group patients who did poorly in terms of 433
continued abdominal pain and recurrent episodes of pancreatitis subsequently had stent placement into their dorsal pancreatic duct. These patients have done extremely well and have not experienced any further attacks of pancreatitis. In a prospective clinical trial, improvement following endoscopic stent placement across the minor papilla in patients with acute recurrent pancreatitis and pancreas divisum suggested that relief may be obtained from subsequent definitive surgical sphincteroplasty. Those patients that did well endoscopically did well following operation. I5 Several disadvantages following pancreatic stent placement have been reported, including structural alterations in the pancreatic duct simulating those observed with chronic pancreatitis and overt ductal strictures. I6 Additionally the stent may migrate into or out of the pancreatic duct. Inward migration may require operative intervention to remove the foreign body. We have reported that pancreatic ductal changes occur in the majority of patients undergoing endoscopic stent therapy, but these alterations are for the most part reversible following stent removal. However, pancreatic duct stenting has been associated with a 7% rate of ductal stricturing and these patients may progress to chronic pancreatitis. I? In this study, the length of the stent was varied with each stent exchange. No episodes of pancreatic ductal stricturing were observed. The prolonged exposure of anyone portion of the pancreatic duct to the end of the endoprosthesis may cause pancreatic duct stricturing. Altering the length of the stent at short intervals can, therefore, possibly prevent this localized complication. In a recent study, our group has shown that modification of pancreatic duct stent by removal of the two inner barbs also reduces the rate of intraductal migration of the stents. I8 We have demonstrated that dorsal pancreatic duct stent therapy in patients with acute recurrent pancreatitis and pancreas divisum results in significant objective and subjective improvement in short-term follow-up. The long-term implications of endoprosthesis treatment are unknown; stenting may result in dilation of the minor papillary sphincter. The results of this study suggest that impairment of pancreatic
434
drainage by the minor papilla may be an etiology for recurrent pancreatitis in patients with pancreas divisum.
REFERENCES 1. Dawson W, Langman J. An anatomic radiologic study on pancreatic duct pattern in man. Anat Rec 1961;39:59-68. 2. Cotton PB. Congenital anomaly of pancreas divisum as a cause of obstructive pain and pancreatitis. Gut 1980;21:105-14. 3. Richter JM, Schapiro RH, Mulley AC, et al. Association of pancreas divisum and pancreatitis and its treatment by sphincteroplasty of the accessory ampulla. Gastroenterology 1981;81:1104-10. 4. Gregg JA. Pancreas divisum: its association with pancreatitis. Am J Surg 1977;134:539-43. 5. Delhaye M, Engelholm L, Cremer M. Pancreas divisum: congenital anatomic variant or anomaly. Contribution of endoscopic retrograde dorsal pancreatography. Gastroenterology 1985;89:951-8. 6. Britt L, Samuels A. Pancreas divisum: is it a surgical disease? Ann Surg 1983;197:654-61. 7. Carey L. Pancreas divisum. American Gastroenterological Association Postgraduate Course, May 1985, p 83. 8. Satterfield ST, McCarthy JH, Geenen JE, et al. Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy. Pancreas 1988;3:24853. 9. Russell CG, Wong W, Cotton PH. Accessory sphincterotomy (endoscopic and surgical) in patients with pancreas divisum. Br J Surg 1984;71:954-7. 10. Lehman G, O'Connor K, Troiano F, Benage D. Endoscopic papillotomy and stenting of the minor papilla in pancreas divisum [Abstract). Gastrointest Endosc 1989;35:167. 11. Prabhu M, Geenen JE, Hogan WJ, et al. Role of endoscopic stent placement in the treatment of acute recurrent pancreatitis associated with pancreas divisum: a prospective assessment [Abstract). Gastrointest Endosc 1989;35:165. 12. Warshaw AL. Pancreas divisum: a case for surgical treatment. Adv Surg 1988;21:93. 13. Gregg JA. The intraductal secretin test (IDST). An adjunct to the diagnosis of pancreatic disease and pancreatic physiology. In: Sivak M, ed. Gastroenterologic endoscopy. Philadelphia: WB Saunders, 1987:794-807. 14. Geenen JE. A/S/G/E distinguished lecture-endoscopic therapy of pancreatic disease: a new horizon. Gastrointest Endosc 1988;34:386-9. 15. Siegel JH, Ben-Zvi JS, Pullano W, Cooperman A. Effectiveness of endoscopic drainage for pancreas divisum: endoscopic and surgical results in 31 patients. Endoscopy 1990;22:129-33. 16. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 1990;36:93. 17. Derfus GA, Geenen JE, Hogan WJ. Alterations in pancreatic duct morphology associated with endoscopic stent placement [Abstract). Pancreas 1989;5:613. 18. Johanson JF, Schmalz MJ, Geenen JE. Migration of pancreatic duct stents prevented by a simple modification [Abstract). Gastrointest Endosc 1991;37:272.
GASTROINTESTINAL ENDOSCOPY
