Int. J. Pancreatol. @) Copyright 1991 by The Humana Press Inc. All rights of any nature whatsoever reserved. 0169-4197/91/10(1): 097-102/$2.00
Views: Pro and Con
Do Gallstones Cause Chronic Pancreatitis? S.P. Misra * a n d Alanisha Dwivedi Department o f Gastroenterology. M. L. N. Medical College, Allahabad-211 001, lndia Received January 2, 1991; Accepted February 2l, 1991
Summary Gallstones are well known to cause acute pancreatitis. However, the role of gallstone disease in the causation of chronic pancreatitis is still controversial. Abnormalities of the pancreatic duct have been noted in about one-half of patients with calculous biliary disease undergoing endoscopic retrograde cholangiopancreatography (ERCP), but despite this, it is generally believed that gallstones rarely, if ever, cause chronic pancreatitis. The clinical significance and the natural history of the pancreatographic changes seen in patients with gallstone disease is not known. Studies of the pancreatic functions and long-term follow-up of patients with calculous biliary disease, especially those who have abnormal pancreatograms, and the effect of removal of the gallstone on the pancreatographic abnormalities and pancreatic functions are needed to clarify the issue. Key Words: Gallstones; chronic pancreatitis; ERCP. INTRODUCTION Although it is established beyond doubt that gallstones are associated with acute pancreatitis (1-10), their role in causation of chronic pancreatitis, although mentioned in some studies (11, 12), is controversial and it is generally believed that gallstones rarely, if ever, cause chronic pancreatitis (13). However, abnormalities in the pancreas have been noted in 45~ o f 1169 patients with gallstones (14). Endoscopic retrograde cholangiopancreatographic (ERCP) studies have also noted abnormal pancreatograms in patients with gallstones (15-17). The significance o f these findings is still not clear. *Author to whom all correspondence and reprint requests should be addressed.
International Journal of Pancreatology
97
Volume I0, 1991
98
Misra and Dwivedi
Satke et al. (15) were the first to observe abnormal pancreatograms in patients with gallstones. They noted marked dilation of the main pancreatic duct (MPD) in 13 (72~ of 18 patients with choledocholithiasis, in whom the pancreatic duct could be outlined. Seven (33~ of 20 patients with cholelithiasis also showed marked dilation of the MPD. The difference between the two groups (though not calculated in the study) was statistically significant (X 2 = 5.2, p < 0.05). However, the exact measurements were not available, and whether or not the dilations qualified to be classified as chronic pancreatitis by the Cambridge classification (17a) is debatable. The authors used the adjective 'marked' dilation, whereby it may be presumed that the dilation would have been considerable. If this was so, then about 52% of patients having gallstones would be expected to have ERCP changes of chronic pancreatitis. However, on closer scrutiny of the study, some doubts are raised; such as in a figure that showed choledocholithiasis and marked dilation of the MPD, the lower end of the common bile duct (CBD) showed a stricture. Since the clinical features and pancreatic functions were not known, it can be argued that choledocholithiasis, in this patient, was secondary to the stricture in the CBD, owing to chronic pancreatitis; the evidence of which is the markedly dilated MPD. Occurrence of jaundice and gallstones in patients with pancreatitis having stricture of the CBD is well known (18). In a review, Howard and Jones (19) noted that 35 and 8% of patients with relapsing pancreatitis had cholelithiasis and choledocholithiasis, respectively. Axon et al. (16), in a study of ERCPs of 53 patients with calculous biliary disease, noted abnormalities of the pancreatograms in 25 (46.4%) of these patients. Abnormalities were noted in 13 (47~ of 28 patients who presented with jaundice and 12 (48%) of 25 patients who presented with pain. In contrast, pancreatogram abnormalities were noted in only one (8%) of 12 'controls' who were patients with hepatitis or nonpancreatic neoplasia. The authors concluded that asymptomatic chronic pancreatitis may be a common occurrence in patients with calculous biliary disease. Although these studies showed abnormal pancreatograms in patients with gallstone disease, one of the studies (15) did not take into consideration the effect of aging and alcohol on the pancreatic ductal changes. However, Axon et al. (16) noted that patients with abnormal pancreatograms were older than those with normal pancreatograms. It has been shown that with increasing age, the pancreatic duct tends to dilate (19-22) although not all workers agree with this (23,24). In an autopsy study, mild abnormalities of the pancreatic ductal system were noted in about 25% of normal persons aged > 45 yr (25). In a Japanese study, ductal calculi were noted in older subjects who were otherwise healthy. No calculi were seen in those < 65 yr, but 4.2% o f subjects aged 70-79 yr and 16.7~ of those in the 90s showed evidence of calculi (26). In a recent retrospective study of ERCPs of 50 nonalcoholic patients with gallstones (17), we noted abnormal pancreatograms in 24 (48%) of patients compared to only 2 (6%) of 33 patients having cholestatic jaundice owing to viral hepatitis (control group). When classified by the Cambridge classifica-
lnternaltot~e/ Journal o f Pencreatology
~ohtme 10. 199l
Gallstones and Chronic Pancreatitis
99
tion, with minor modifications, the abnormalities were noted to be mild in 32%, moderate in 10070, and severe in 6% of patients, i.e., 16% of the pancreatograms qualified to be labeled as that of chronic pancreatitis. In the 'control' group, both patients had only mild abnormalities. Abnormalities of the pancreatic duct were more severe and more frequent (55 vs 25~ in those with choledocholithiasis than those who had undergone cholecystectomy in the past. Age was found not to influence the pancreatographic abnormalities in these patients. Again, since it was a retrospective study, pancreatic functions and fat malabsorption tests were not available. All three studies mentioned above noted abnormal pancreatograms in about one-half of the patients with calculous biliary disease. In two studies (15,17), these abnormalities were noted more frequently in patients with choledocholithiasis than in those with cholelithiasis (15) or patients in whom cholecystectomy was performed in the past for cholelithiasis (17). It therefore appears that presence of stones in the CBD somehow affects the pancreas more than just by being present in the gallbladder. The exact mechanism of pancreatic damage in patients with gallstones is not clear. It has been speculated that gallstones may damage the pancreatic duct while passing through the ampulla of Vater (17). This theory entails that there should be a transient obstruction to the common pancreaticobiliary channel. However, in an earlier study (27), it has been shown that the majority (70%) of patients with gallstones have separate openings, as seen at ERCP. It might be possible, that only patients with gallstones having a common channel may show abnormal pancreatograms. Unfortunately, in our study (17), the common channel or separate openings were not clearly seen in the same film, in the majority of patients, to enable us to draw conclusions regarding the prevalence of common channel in these patients. Planned ERCP studies are needed to clarify this issue. Furthermore, studies in patients with alcoholic chronic pancreatitis, have shown that patients having separate openings of the CBD and MPD are more predisposed to develop the disease (28). In another study, we have noted separate openings of the CBD and MPD in 72~ of 18 patients with alcoholic chronic pancreatitis compared to 45070 in those with idiopathic chronic pancreatitis (28a). Therefore, the morphological abnormalities in the pancreas of patients with gallstones appear to be caused by a different mechanism. One important aspect of these studies showing abnormalities of the pancreatograms in patients with gallstones is that, most patients were asymptomatic, in the sense that classical pancreatic pain was not present. This might be the natural history of 'gallstone induced chronic pancreatitis,' but is contrary to that of classical chronic pancreatitis in which the majority of patients complain of pain (13). The natural history of 'gallstone induced chronic pancreatitis' is not known. Whether the pancreatographic changes regress, are stationary, or progress with time as such or after removal of gallstones is not clearly known. In the study by Axon et al. (16), 21 patients had been operated on for gallstones in the past and 43% of these patients had abnormal pancreatograms. The authors
International Journal o f Pancreatol~.v
Volume I0, 1991
100
Misra and Dwivedi
were of the opinion that such patients continue to have pancreatogram changes following successful biliary surgery. However, it was not known how far back the surgery was performed and whether or not these changes were present before surgery. It would be ideal to perform surgery or sphincterotomy for removal of stones in patients with gallstone disease who show abnormal pancreatograms, and to follow the pancreatographic changes. In our study (17), changes in the pancreatograms were more severe and more frequent in those demonstrating stones in the CBD than in those whose CBD was clear of stones. Similarly, pancreatic exocrine and endocrine functions should also be investigated. In this regard, it is of interest that Marks and Bank (29) have noted abnormal pancreatic function in about 10% of patients after gallstone pancreatitis. Abnormal pancreatograms were also seen in a number of patients with postcholecystectomy syndrome (18). Whether or not these patients were symptomatic because of chronic pancreatitis is conjectural. Another study, in patients with acute pancreatitis, observed changes of chronic pancreatitis in 8 (40%) of 20 patients in whom the pancreatic duct was visualized (30). It is well known that strictures may form in the pancreatic duct following a severe attack of gallstone-induced acute pancreatitis (18). This scar may lead to chronic obstructive pancreatitis. If this is the mechanism responsible for pancreatographic changes, then an open biopsy of the pancreas from such patients would be extremely helpful. Patients with chronic obstructive pancreatitis show diffuse atrophy of acinar parenchyma and uniform diffuse fibrosis, as opposed to irregular sclerosis and either focal, segmental, or diffuse loss of acini seen in patients with classical chronic pancreatitis. Furthermore, these changes would improve if the lesion is surgically corrected (31). Patients with gallstone disease with abnormal pancreatograms should be followed up for sufficiently long periods to look for development of pain, worsening of pancreatic exocrine and endocrine functions, and appearance of pancreatic calcification. However, development of calcification, overt diabetes mellitus, or steatorrhea are virtually not known in obstructive chronic pancreatitis; although the insulin reserve and exocrine functions of the pancreas might be impaired (18). In conclusion, about one-half of patients with gallstone disease show abnormalities in the pancreatograms, and may have ERCP changes of chronic pancreatitis. However, the clinical relevance of these abnormal pancreatograms and its natural history is still not clear. Well planned, prospective studies to follow the natural history, the effect of interventions, such as endoscopic or surgical removal of stones, and study of the pancreatic exocrine and endocrine functions will clarify the issue whether these ERCP and morphological changes are part of a true chronic pancreatitis or not. Until then, it can be assumed that gallstones rarely, if ever, cause chronic pancreatitis.
REFERENCES I
Glenn F, Frey C. Re-evaluation of the treatment of pancreatitis associated with biliary tract disease. Ann. Surg. 1964; 160: 723-736.
International Journal o f Pancreatology
~-blume 10, 1991
Gallstones and Chronic Pancreatitis 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 17a 18 19 20 21 22 23 24 25
101
Dixon JA, Hillam JD. Surgical treatment of biliary tract disease associated with acute pancreatitis. Am. J. Surg. 1970; 120: 371-375. Acosta JM, Ledesma CL. Gallstone migration as a cause of acute pancreatitis. N. Engl. J. Med. 1974; 290: 484-487. Kelly TR. Gallstone pancreatitis: pathophysiology. Surgery 1976; 80: 488-492. Imrie W, Whyte AS. A prospective study of acute pancreatitis. Br. J. Surg. 1975; 62: 490-494. Freund H, Pfeffermann R, Durst AL, Rabinovici N. Gallstone pancreatitis. Exploration of the biliary system in acute and recurrent pancreatitis. Arch. Surg. 1976; 111:1106-1107. Ong GB, Lam KH, Lim SK, t.im TK, Wong J. Acute pancreatitis in Hong-Kong. Br. J. Surg. 1979; 66: 398--403. Ranson JHC. The timing of biliary surgery in acute pancreatitis. Ann. Surg. 1979; 189: 654-663. Kelly TR, Swaney PE. Gallstone pancreatitis: the second time around. Surgery 1982; 92: 571-575. Jones BA, Salsberg BB, Bohnen JMA, Mehta MH. Common pancreaticobiliary channels and their relationship to gallstone size in gallstone pancreatitis. Ann. Surg. 1987; 205: 123-128. James O, Agnew JE, Bouchier IAD. Chronic pancreatitis in England: A changing picture? Br. Med. J. 1974; 2: 34-38. Read G, Braganza JM, Howat HJ. Pancreatitis--a retrospective study. Gut 1976; 17: 945-952. Grendell JH, Cello JP. Chronic pancreatitis. Sleisenger MH, Fordtran JS Eds. Gastrointestinal diseases: Pathophysiology, Diagnosis, Management, 5th Edition. WB Saunders, Philadelphia, PA, 1989; 1842-1872. Miyake H, Shimura H. Gendai Gekagaker Taikei. Recent trends of surgery, liver and biliary tree. vol. II, Nakayama Book, Tokyo, 1971: 38-41. Satke K, Umeyama K, Kobayashi K, Mitani E, Tatsumi S, Yamamoto S, Hov, ard JM. An evaluation of endoscopic pancreaticocholangiography in surgical patients. Surg. Gynecol. Obstet. 1975; 140: 349-354. Axon ATR, Ashton MG, Lintott DJ. Pancreatogram changes in patients with calculous biliary disease. Br. J. Surg. 1979; 66: 466-470. Misra SP, Gulati P, Choudhary V, Anand BS. Pancreatic duct abnormalities in gallstone disease: An endoscopic retrograde cholangiopancreatographic study. Gut 1990; 31: 1073-1075. Axon ATR, Classen M, Cotton PB, Cremer M, Freeny PC, Lees WR. Pancreatography in chronic pancreatitis: International definitions. Gut 1984; 25:1107-1112. Bank S. Chronic pancreatitis: Clinical features and medical management. Am. J. Gastroenterol 1986; 81: 153-167. Kreel L, Sandin S. Changes in pancreatic morphology associated with aging. Gut 1973; 141 : 462-470. MacCarty RL, Stephen DH, Brown JAL, Carlson HC. Retrograde pancreatography in autopsy specimens. AJR 1975; 123: 359-366. Oi I. Duodenoscopy during pancreatic disease. Arch. France Mal. Appar. Dig. 1972; 61: 349-354. Anand BS, Vij JC, Mac HS, Choudhury V, Kumar A. Effect of aging on the pancreatic ducts: a study based on endoscopic retrograde pancreatography. Gastrointest. Endosc. 1989; 35: 2t0-213. Kasugai T, Kono N, Kobayashi S, Hattori K. Endoscopic pancreatocholangiography. I. The normal endoscopic pancreatocholangiogram. Gastroenterology 1972; 63: 217-226. Verly PF, Rohrmann CA Jr, Silvis SE, Vennes JA. The normal endoscopic pancreatogram. Radiology 1976; 118: 295-300. Schmitz-Moormann P, Riedel R, lhm P. Morphometrische Untersuchungen der Kaliberschewankungen an normalen Duetu pancreaticus major. Z. Gastroenterol. t981; t9: 299-306.
International Journal o f Pancreatolog.v
l.?)lume 10, I991
102 26 27 28 28a 29 30 31
Misra and Dwivedi Nagai H, Ohtsubo K. Pancreatic lithiasis in the aged. Its clinicopathology and pathogenesis. Gastroenterology 1984; 86: 331-338. Misra SP, Gulati P, Thorat VK, Vij JC, Anand BS. Pancreaticobiliary ductal union in biliary diseases: An endoscopic retrograde cholangiopancreatographic study. Gastroenterology 1989; 96: 907-912. Yatto RP, Siegel JH. The role of pancreaticobiliary duct anatomy in the etiology o f alcoholic pancreatitis. J. Clin. Gastroenterol. 1984; 6: 419-423. Misra SP, Gulati P, Anand BS. Pancreaticobiliary ductal union in chronic pancreatitis. Ind. J. Gastroenterol. 1991; 10 (in press). Marks IN, Bank S. Chronic Pancreatitis. Etiology, Clinical aspects, and Medical Management, Berk JE, Hanbrich WS, Kaiser MH, Roth JLA, Schaffner F, eds. Bockus Gastroenterology, 5th Ed. WB Saunders, Philadelphia, PA, 1985; 4020-4040. Hamilton I, Bradley P, Lintott D J, McMahon M J, Axon ATR. Endoscopic retrograde cholangiopancreatography in the investigation and management of patients after acute pancreatitis. Br. J. Surg. 1982; 69: 504-506. Sarles H. Etiopathogenesis and definition of chronic pancreatitis. Dig. Dis. Sci. 1986; 31 (Suppl): 91S- 107S.
International Journal o f Pancreatolog)"
Volume I0, 199t
Views: Pro and Con
Do Gallstones Cause Chronic Pancreatitis? S.P. Misra * a n d Alanisha Dwivedi Department o f Gastroenterology. M. L. N. Medical College, Allahabad-211 001, lndia Received January 2, 1991; Accepted February 2l, 1991
Summary Gallstones are well known to cause acute pancreatitis. However, the role of gallstone disease in the causation of chronic pancreatitis is still controversial. Abnormalities of the pancreatic duct have been noted in about one-half of patients with calculous biliary disease undergoing endoscopic retrograde cholangiopancreatography (ERCP), but despite this, it is generally believed that gallstones rarely, if ever, cause chronic pancreatitis. The clinical significance and the natural history of the pancreatographic changes seen in patients with gallstone disease is not known. Studies of the pancreatic functions and long-term follow-up of patients with calculous biliary disease, especially those who have abnormal pancreatograms, and the effect of removal of the gallstone on the pancreatographic abnormalities and pancreatic functions are needed to clarify the issue. Key Words: Gallstones; chronic pancreatitis; ERCP. INTRODUCTION Although it is established beyond doubt that gallstones are associated with acute pancreatitis (1-10), their role in causation of chronic pancreatitis, although mentioned in some studies (11, 12), is controversial and it is generally believed that gallstones rarely, if ever, cause chronic pancreatitis (13). However, abnormalities in the pancreas have been noted in 45~ o f 1169 patients with gallstones (14). Endoscopic retrograde cholangiopancreatographic (ERCP) studies have also noted abnormal pancreatograms in patients with gallstones (15-17). The significance o f these findings is still not clear. *Author to whom all correspondence and reprint requests should be addressed.
International Journal of Pancreatology
97
Volume I0, 1991
98
Misra and Dwivedi
Satke et al. (15) were the first to observe abnormal pancreatograms in patients with gallstones. They noted marked dilation of the main pancreatic duct (MPD) in 13 (72~ of 18 patients with choledocholithiasis, in whom the pancreatic duct could be outlined. Seven (33~ of 20 patients with cholelithiasis also showed marked dilation of the MPD. The difference between the two groups (though not calculated in the study) was statistically significant (X 2 = 5.2, p < 0.05). However, the exact measurements were not available, and whether or not the dilations qualified to be classified as chronic pancreatitis by the Cambridge classification (17a) is debatable. The authors used the adjective 'marked' dilation, whereby it may be presumed that the dilation would have been considerable. If this was so, then about 52% of patients having gallstones would be expected to have ERCP changes of chronic pancreatitis. However, on closer scrutiny of the study, some doubts are raised; such as in a figure that showed choledocholithiasis and marked dilation of the MPD, the lower end of the common bile duct (CBD) showed a stricture. Since the clinical features and pancreatic functions were not known, it can be argued that choledocholithiasis, in this patient, was secondary to the stricture in the CBD, owing to chronic pancreatitis; the evidence of which is the markedly dilated MPD. Occurrence of jaundice and gallstones in patients with pancreatitis having stricture of the CBD is well known (18). In a review, Howard and Jones (19) noted that 35 and 8% of patients with relapsing pancreatitis had cholelithiasis and choledocholithiasis, respectively. Axon et al. (16), in a study of ERCPs of 53 patients with calculous biliary disease, noted abnormalities of the pancreatograms in 25 (46.4%) of these patients. Abnormalities were noted in 13 (47~ of 28 patients who presented with jaundice and 12 (48%) of 25 patients who presented with pain. In contrast, pancreatogram abnormalities were noted in only one (8%) of 12 'controls' who were patients with hepatitis or nonpancreatic neoplasia. The authors concluded that asymptomatic chronic pancreatitis may be a common occurrence in patients with calculous biliary disease. Although these studies showed abnormal pancreatograms in patients with gallstone disease, one of the studies (15) did not take into consideration the effect of aging and alcohol on the pancreatic ductal changes. However, Axon et al. (16) noted that patients with abnormal pancreatograms were older than those with normal pancreatograms. It has been shown that with increasing age, the pancreatic duct tends to dilate (19-22) although not all workers agree with this (23,24). In an autopsy study, mild abnormalities of the pancreatic ductal system were noted in about 25% of normal persons aged > 45 yr (25). In a Japanese study, ductal calculi were noted in older subjects who were otherwise healthy. No calculi were seen in those < 65 yr, but 4.2% o f subjects aged 70-79 yr and 16.7~ of those in the 90s showed evidence of calculi (26). In a recent retrospective study of ERCPs of 50 nonalcoholic patients with gallstones (17), we noted abnormal pancreatograms in 24 (48%) of patients compared to only 2 (6%) of 33 patients having cholestatic jaundice owing to viral hepatitis (control group). When classified by the Cambridge classifica-
lnternaltot~e/ Journal o f Pencreatology
~ohtme 10. 199l
Gallstones and Chronic Pancreatitis
99
tion, with minor modifications, the abnormalities were noted to be mild in 32%, moderate in 10070, and severe in 6% of patients, i.e., 16% of the pancreatograms qualified to be labeled as that of chronic pancreatitis. In the 'control' group, both patients had only mild abnormalities. Abnormalities of the pancreatic duct were more severe and more frequent (55 vs 25~ in those with choledocholithiasis than those who had undergone cholecystectomy in the past. Age was found not to influence the pancreatographic abnormalities in these patients. Again, since it was a retrospective study, pancreatic functions and fat malabsorption tests were not available. All three studies mentioned above noted abnormal pancreatograms in about one-half of the patients with calculous biliary disease. In two studies (15,17), these abnormalities were noted more frequently in patients with choledocholithiasis than in those with cholelithiasis (15) or patients in whom cholecystectomy was performed in the past for cholelithiasis (17). It therefore appears that presence of stones in the CBD somehow affects the pancreas more than just by being present in the gallbladder. The exact mechanism of pancreatic damage in patients with gallstones is not clear. It has been speculated that gallstones may damage the pancreatic duct while passing through the ampulla of Vater (17). This theory entails that there should be a transient obstruction to the common pancreaticobiliary channel. However, in an earlier study (27), it has been shown that the majority (70%) of patients with gallstones have separate openings, as seen at ERCP. It might be possible, that only patients with gallstones having a common channel may show abnormal pancreatograms. Unfortunately, in our study (17), the common channel or separate openings were not clearly seen in the same film, in the majority of patients, to enable us to draw conclusions regarding the prevalence of common channel in these patients. Planned ERCP studies are needed to clarify this issue. Furthermore, studies in patients with alcoholic chronic pancreatitis, have shown that patients having separate openings of the CBD and MPD are more predisposed to develop the disease (28). In another study, we have noted separate openings of the CBD and MPD in 72~ of 18 patients with alcoholic chronic pancreatitis compared to 45070 in those with idiopathic chronic pancreatitis (28a). Therefore, the morphological abnormalities in the pancreas of patients with gallstones appear to be caused by a different mechanism. One important aspect of these studies showing abnormalities of the pancreatograms in patients with gallstones is that, most patients were asymptomatic, in the sense that classical pancreatic pain was not present. This might be the natural history of 'gallstone induced chronic pancreatitis,' but is contrary to that of classical chronic pancreatitis in which the majority of patients complain of pain (13). The natural history of 'gallstone induced chronic pancreatitis' is not known. Whether the pancreatographic changes regress, are stationary, or progress with time as such or after removal of gallstones is not clearly known. In the study by Axon et al. (16), 21 patients had been operated on for gallstones in the past and 43% of these patients had abnormal pancreatograms. The authors
International Journal o f Pancreatol~.v
Volume I0, 1991
100
Misra and Dwivedi
were of the opinion that such patients continue to have pancreatogram changes following successful biliary surgery. However, it was not known how far back the surgery was performed and whether or not these changes were present before surgery. It would be ideal to perform surgery or sphincterotomy for removal of stones in patients with gallstone disease who show abnormal pancreatograms, and to follow the pancreatographic changes. In our study (17), changes in the pancreatograms were more severe and more frequent in those demonstrating stones in the CBD than in those whose CBD was clear of stones. Similarly, pancreatic exocrine and endocrine functions should also be investigated. In this regard, it is of interest that Marks and Bank (29) have noted abnormal pancreatic function in about 10% of patients after gallstone pancreatitis. Abnormal pancreatograms were also seen in a number of patients with postcholecystectomy syndrome (18). Whether or not these patients were symptomatic because of chronic pancreatitis is conjectural. Another study, in patients with acute pancreatitis, observed changes of chronic pancreatitis in 8 (40%) of 20 patients in whom the pancreatic duct was visualized (30). It is well known that strictures may form in the pancreatic duct following a severe attack of gallstone-induced acute pancreatitis (18). This scar may lead to chronic obstructive pancreatitis. If this is the mechanism responsible for pancreatographic changes, then an open biopsy of the pancreas from such patients would be extremely helpful. Patients with chronic obstructive pancreatitis show diffuse atrophy of acinar parenchyma and uniform diffuse fibrosis, as opposed to irregular sclerosis and either focal, segmental, or diffuse loss of acini seen in patients with classical chronic pancreatitis. Furthermore, these changes would improve if the lesion is surgically corrected (31). Patients with gallstone disease with abnormal pancreatograms should be followed up for sufficiently long periods to look for development of pain, worsening of pancreatic exocrine and endocrine functions, and appearance of pancreatic calcification. However, development of calcification, overt diabetes mellitus, or steatorrhea are virtually not known in obstructive chronic pancreatitis; although the insulin reserve and exocrine functions of the pancreas might be impaired (18). In conclusion, about one-half of patients with gallstone disease show abnormalities in the pancreatograms, and may have ERCP changes of chronic pancreatitis. However, the clinical relevance of these abnormal pancreatograms and its natural history is still not clear. Well planned, prospective studies to follow the natural history, the effect of interventions, such as endoscopic or surgical removal of stones, and study of the pancreatic exocrine and endocrine functions will clarify the issue whether these ERCP and morphological changes are part of a true chronic pancreatitis or not. Until then, it can be assumed that gallstones rarely, if ever, cause chronic pancreatitis.
REFERENCES I
Glenn F, Frey C. Re-evaluation of the treatment of pancreatitis associated with biliary tract disease. Ann. Surg. 1964; 160: 723-736.
International Journal o f Pancreatology
~-blume 10, 1991
Gallstones and Chronic Pancreatitis 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 17a 18 19 20 21 22 23 24 25
101
Dixon JA, Hillam JD. Surgical treatment of biliary tract disease associated with acute pancreatitis. Am. J. Surg. 1970; 120: 371-375. Acosta JM, Ledesma CL. Gallstone migration as a cause of acute pancreatitis. N. Engl. J. Med. 1974; 290: 484-487. Kelly TR. Gallstone pancreatitis: pathophysiology. Surgery 1976; 80: 488-492. Imrie W, Whyte AS. A prospective study of acute pancreatitis. Br. J. Surg. 1975; 62: 490-494. Freund H, Pfeffermann R, Durst AL, Rabinovici N. Gallstone pancreatitis. Exploration of the biliary system in acute and recurrent pancreatitis. Arch. Surg. 1976; 111:1106-1107. Ong GB, Lam KH, Lim SK, t.im TK, Wong J. Acute pancreatitis in Hong-Kong. Br. J. Surg. 1979; 66: 398--403. Ranson JHC. The timing of biliary surgery in acute pancreatitis. Ann. Surg. 1979; 189: 654-663. Kelly TR, Swaney PE. Gallstone pancreatitis: the second time around. Surgery 1982; 92: 571-575. Jones BA, Salsberg BB, Bohnen JMA, Mehta MH. Common pancreaticobiliary channels and their relationship to gallstone size in gallstone pancreatitis. Ann. Surg. 1987; 205: 123-128. James O, Agnew JE, Bouchier IAD. Chronic pancreatitis in England: A changing picture? Br. Med. J. 1974; 2: 34-38. Read G, Braganza JM, Howat HJ. Pancreatitis--a retrospective study. Gut 1976; 17: 945-952. Grendell JH, Cello JP. Chronic pancreatitis. Sleisenger MH, Fordtran JS Eds. Gastrointestinal diseases: Pathophysiology, Diagnosis, Management, 5th Edition. WB Saunders, Philadelphia, PA, 1989; 1842-1872. Miyake H, Shimura H. Gendai Gekagaker Taikei. Recent trends of surgery, liver and biliary tree. vol. II, Nakayama Book, Tokyo, 1971: 38-41. Satke K, Umeyama K, Kobayashi K, Mitani E, Tatsumi S, Yamamoto S, Hov, ard JM. An evaluation of endoscopic pancreaticocholangiography in surgical patients. Surg. Gynecol. Obstet. 1975; 140: 349-354. Axon ATR, Ashton MG, Lintott DJ. Pancreatogram changes in patients with calculous biliary disease. Br. J. Surg. 1979; 66: 466-470. Misra SP, Gulati P, Choudhary V, Anand BS. Pancreatic duct abnormalities in gallstone disease: An endoscopic retrograde cholangiopancreatographic study. Gut 1990; 31: 1073-1075. Axon ATR, Classen M, Cotton PB, Cremer M, Freeny PC, Lees WR. Pancreatography in chronic pancreatitis: International definitions. Gut 1984; 25:1107-1112. Bank S. Chronic pancreatitis: Clinical features and medical management. Am. J. Gastroenterol 1986; 81: 153-167. Kreel L, Sandin S. Changes in pancreatic morphology associated with aging. Gut 1973; 141 : 462-470. MacCarty RL, Stephen DH, Brown JAL, Carlson HC. Retrograde pancreatography in autopsy specimens. AJR 1975; 123: 359-366. Oi I. Duodenoscopy during pancreatic disease. Arch. France Mal. Appar. Dig. 1972; 61: 349-354. Anand BS, Vij JC, Mac HS, Choudhury V, Kumar A. Effect of aging on the pancreatic ducts: a study based on endoscopic retrograde pancreatography. Gastrointest. Endosc. 1989; 35: 2t0-213. Kasugai T, Kono N, Kobayashi S, Hattori K. Endoscopic pancreatocholangiography. I. The normal endoscopic pancreatocholangiogram. Gastroenterology 1972; 63: 217-226. Verly PF, Rohrmann CA Jr, Silvis SE, Vennes JA. The normal endoscopic pancreatogram. Radiology 1976; 118: 295-300. Schmitz-Moormann P, Riedel R, lhm P. Morphometrische Untersuchungen der Kaliberschewankungen an normalen Duetu pancreaticus major. Z. Gastroenterol. t981; t9: 299-306.
International Journal o f Pancreatolog.v
l.?)lume 10, I991
102 26 27 28 28a 29 30 31
Misra and Dwivedi Nagai H, Ohtsubo K. Pancreatic lithiasis in the aged. Its clinicopathology and pathogenesis. Gastroenterology 1984; 86: 331-338. Misra SP, Gulati P, Thorat VK, Vij JC, Anand BS. Pancreaticobiliary ductal union in biliary diseases: An endoscopic retrograde cholangiopancreatographic study. Gastroenterology 1989; 96: 907-912. Yatto RP, Siegel JH. The role of pancreaticobiliary duct anatomy in the etiology o f alcoholic pancreatitis. J. Clin. Gastroenterol. 1984; 6: 419-423. Misra SP, Gulati P, Anand BS. Pancreaticobiliary ductal union in chronic pancreatitis. Ind. J. Gastroenterol. 1991; 10 (in press). Marks IN, Bank S. Chronic Pancreatitis. Etiology, Clinical aspects, and Medical Management, Berk JE, Hanbrich WS, Kaiser MH, Roth JLA, Schaffner F, eds. Bockus Gastroenterology, 5th Ed. WB Saunders, Philadelphia, PA, 1985; 4020-4040. Hamilton I, Bradley P, Lintott D J, McMahon M J, Axon ATR. Endoscopic retrograde cholangiopancreatography in the investigation and management of patients after acute pancreatitis. Br. J. Surg. 1982; 69: 504-506. Sarles H. Etiopathogenesis and definition of chronic pancreatitis. Dig. Dis. Sci. 1986; 31 (Suppl): 91S- 107S.
International Journal o f Pancreatolog)"
Volume I0, 199t
