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Pancreatitis associated with Crohn’s disease: a premalignant state for cystadenocarcinoma of pancreas?
AJG – August, 1999
4. Boerlsterli UA, Zimmerman HJ, Kretz-Rommel A. Idiosyncratic liver toxicity of nonsteroidal antiinflammatory drugs: Molecular mechanisms and pathology. Crit Rev Toxicol 1995; 25:207–35. 5. Helfgott SM, Sandberg-Cook J, Zakim D, et al. Diclofenacassociated hepatotoxicity. JAMA 1990;264:2660 –2. 6. Scully LJ, Clarke D, Barr RJ. Diclofenac induced hepatitis: 3 Cases with features of autoimmune chronic active hepatitis. Dig Dis Sci 1993;38:744 –51. 7. Dear Health Professional Letter-Duract. Philadelphia, PA: Wyeth Laboratories Inc., February 1998.
Pancreatitis Associated With Crohn’s Disease: A Premalignant State for Cystadenocarcinoma of Pancreas? Amnon Gotian, M.D., and Seymour Katz, M.D., F.A.C.G., F.A.C.P. Department of Medicine, North Shore University Hospital, Manhasset, New York; and New York University School of Medicine, New York, New York
ABSTRACT We report a 74-yr-old woman with Crohn’s disease and acute pancreatitis who, 3 yr after resolution of the latter, developed cystadenocarcinoma of the pancreas. No drug, toxin, or other etiologies including contiguous duodenal involvement were identified as responsible for the pancreatitis, suggesting that pancreatitis was an extraintestinal manifestation of her Crohn’s disease. Could Crohn’s-associated pancreatitis be a premalignant state for cystadenocarcinoma of the pancreas? (Am J Gastroenterol 1999;94: 2301–2302. © 1999 by Am. Coll. of Gastroenterology)
INTRODUCTION The association between pancreatitis and Crohn’s disease has been increasingly recognized (1–3). In several studies, pancreatitis as an extraluminal manifestation of Crohn’s disease itself was the only explanation. We report the first case of Crohn’s-related pancreatitis without contiguous duodenal involvement and with subsequent development of cystadenocarcinoma of the pancreas.
Brief Case Reports
2301
In March 1988 she was readmitted for anemia, weakness, and fatigue. Biopsies of colonic mucosa were negative for inflammation. Subsequent CT of the abdomen and pelvis demonstrated a thickened wall and narrowed lumen of the terminal ileum consistent with inflammatory bowel disease. A small focal abnormality was found in the liver consistent with a small hemangioma. The pancreas was normal. In June 1988, the patient underwent a resection of 31 cm of the terminal ileum with a 5-cm-long segment of attached cecum because of persistent debility. The pathology report described extensive ulcerations and pseudopolyp formation with a small fistula into the mesentery. A follow-up small bowel series in October 1989 showed no evidence of recurrence. A colonoscopy performed in July 1991 revealed normal colonic mucosa. The patient remained asymptomatic and off all medications. In March of 1994, while not taking any medications, the patient developed abdominal pain and underwent ultrasonography of the abdomen. A focal lesion on right lobe of liver was found to be consistent with small hemangioma and dilatation of the pancreatic duct with no discrete mass in the pancreas. The pancreatic body was slightly heterogeneous, consistent with pancreatitis. Her amylase level was 1188 (24 –97 normal), her white blood cells 13,600 with 90% polymorphonuclears, hemoglobin 12.7, hematocrit 38.0, and platelets 231. Serum amylase fell to 346 (normal 34 – 122), lipase 130 (normal ⬍ 60), total bilirubin 0.8, albumin 3.3, alkaline phosphatase 58, AST 18, ALT 18, CPK 45, LDH 154, and calcium 8.8. A computed tomography scan of the abdomen and pelvis was consistent with the clinical history of pancreatitis. No biliary tract stones or disease were identified. A suggestion of possible duodenal wall thickening was believed to be secondary to the surrounding peripancreatic inflammation. The pancreatitis resolved shortly afterward, and the patient was discharged 6 days later with an amylase level of 44. The patient continued to remain asymptomatic with normal amylase levels until June 1997, when she noted weight loss and
CASE REPORT A 74-yr-old white woman of Hungarian descent was admitted in 1987 to the hospital with intermittent melena and black stool. Her past medical history included mitral valve prolapse, uterine prolapse, chronic urinary tract infections, bilateral carotid disease, and bilateral subtotal thyroidectomy for benign nodules, and 15 years of “irritable bowel syndrome.” Esophagogastroscopy, sigmoidoscopy, and subsequent colonoscopy were all negative. Enteroclysis showed extensive ileitis, ulcerations, and pseudopolyposis consistent with Crohn’s disease.
Figure 1. CT scan of abdomen demonstrating 6 ⫻ 3-cm mass on the head of the pancreas.
2302
Brief Case Reports
altered bowel movements. A large cystic, necrotic appearing mass 6 ⫻ 3 cm was found on the head of the pancreas on computed tomography of the abdomen (Fig. 1). The mass appeared to communicate with both distal common bile duct and pancreatic duct consistent with a neoplasm of the pancreas. A subsequent magnetic resonant cholangiogram and angiogram revealed vessels free of tumor, but tumor was encroaching the portal vein. There was no evidence of distant metastasis. In July 1997 the patient underwent pancreatoduodenectomy with resection of the duodenum and head of pancreas. A multicystic mucinous adenocarcinoma and cystadenoma largely replaced the head of the pancreas. The tumor was found extending into the wall of the duodenum and ampullary region, causing mucosal ulceration with a duodenal ampullary fistula. There was no gross evidence of Crohn’s disease in the residual bowel at time of surgery. Ten lymph nodes and the resected margins were free of tumor. The patient was discharged on a low fat diet with a jejunostomy for supplemental feeding. The latter was subsequently discontinued and she has fared well for 1.5 years of observation.
DISCUSSION An increase in reported cases of pancreatitis in patients with Crohn’s disease has been highly suggestive of their association (1–3). In many cases, no etiological factors were found except for Crohn’s disease itself, indicating pancreatitis as an extraintestinal complication of Crohn’s. In 1950, Ball et al. (4) were the first to suggest the association between pancreatitis and inflammatory bowel disease. Pancreatitis associated with inflammatory bowel disease is most often ascribed to biliary tract disease and to medications such as azathioprine, 6-mercaptopurine, corticosteroids, 5-aminosalicyclic acid, sulfasalazine, metronidazole, and intravenous lipid emulsions (5). Gschwantler et al. (6) described a patient with granulomatous inflammation caused by Crohn’s disease. The involved areas included the stomach, duodenum, and the head of the pancreas, suggesting contiguous pancreatic involvement of Crohn’s disease. Subsequently, cases of pancreatitis with duodenal involvement of Crohn’s disease, excluding other etiologies, were reported (7, 8). Pancreatitis without Crohn’s involvement of the duodenum, drugs, or other known etiological factors suggests its role as an extraintestinal manifestation of Crohn’s disease (7). Although pancreatic cancer associated with pancreatitis is well described, it has always been described in a setting of chronic pancreatitis (9). We present an unusual case of Crohn’s disease with acute pancreatitis with complete resolution, then, after 3 yr, the development of pancreatic cancer. Our patient lacked a history of biliary tract disease, drug exposure, or contiguous Crohn’s disease involving the duodenum. The head of the pancreas was replaced with
AJG – Vol. 94, No. 8, 1999
multicystic mucinous adenocarcinoma. Could Crohn’s-associated pancreatitis be a premalignant state for cystadenocarcinoma of the pancreas? Reprint requests and correspondence: Seymour Katz, M.D., F.A.C.P., F.A.C.G., 1000 Northern Boulevard, Great Neck, NY 11021. Received Apr. 6, 1998; accepted Jan. 27, 1999.
REFERENCES 1. Meyers S, Greenspan J, Greenstein AJ, et al. Pancreatitis coincident with Crohn’s ileocolitis. Report of a case and a review of the literature. Dis Colon Rectum 1987;30:119 –22. 2. Matsumoto T, Matusi T, Iida M, et al. Acute pancreatitis as a complication of Crohn’s disease. Am J Gastroenterol 1989;84: 804 –7. 3. Niemela S, Lehtola J, Karrtunen T, et al. Pancreatitis in patients with chronic inflammatory bowel disease. Hepatogastroenterology 1989;36:175–7. 4. Ball PW, Baggenstoss AH, Bargen JA. Pancreatic lesions associated with chronic ulcerative colitis. Arch Pathol 1950;50:347–58. 5. Weber P, Seibold F, Jenss H. Acute pancreatitis in Crohn’s disease. J Clin Gastroenterol 1993;17:286 –91. 6. Gschwantler M, Kogelbauer G, Klose W, et al. The pancreas as a site of granulomatous inflammation in Crohn’s disease. Gastroenterology 1995;108:1246 –9. 7. Eisner TS, Goldman IS, McKinley MJ. Crohn’s disease and pancreatitis. Am J Gastroenterol 1993;88:583– 6. 8. Legge DA, Carlson HC, Judd ES. Roentgenologic features of regional enteritis of the upper gastrointestinal tract. Am J Roentgenol Radium Ther Nucl Med 1970;110:355– 60. 9. Ho HS, Frey CF. Current approach to the surgical management of chronic pancreatitis. Gastroenterologist 1997;5:128 –36.
Amitriptyline Absorption in a Patient With Short Bowel Syndrome Brett Robbins, M.D., and Robert A. Reiss, Pharm. D., B.C.P.S. Departments of Medicine and Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester; Department of Medicine and Pediatrics, and Department of Pharmacy Practice, ViaHealth, Rochester General Hospital, Rochester, New York
ABSTRACT Oral drug therapy in patients with short bowel syndrome can be quite challenging. We report the case of a 40-yr-old woman with short bowel syndrome and depression requiring antidepressant drug therapy. After buccal administration of amitriptyline, therapeutic serum antidepressant concentrations were attained despite the patient having only 18 inches of proximal small bowel. Clinical improvement in mood was seen, with the only drug side effects being dry mouth and bitter drug taste. Buccal absorption likely is playing a major role in attaining therapeutic serum tricyclic antidepressants drug concentrations. (Am J Gastroenterol 1999;94:2302–2304. © 1999 by Am. Coll. of Gastroenterology)
4. Boerlsterli UA, Zimmerman HJ, Kretz-Rommel A. Idiosyncratic liver toxicity of nonsteroidal antiinflammatory drugs: Molecular mechanisms and pathology. Crit Rev Toxicol 1995; 25:207–35. 5. Helfgott SM, Sandberg-Cook J, Zakim D, et al. Diclofenacassociated hepatotoxicity. JAMA 1990;264:2660 –2. 6. Scully LJ, Clarke D, Barr RJ. Diclofenac induced hepatitis: 3 Cases with features of autoimmune chronic active hepatitis. Dig Dis Sci 1993;38:744 –51. 7. Dear Health Professional Letter-Duract. Philadelphia, PA: Wyeth Laboratories Inc., February 1998.
Pancreatitis Associated With Crohn’s Disease: A Premalignant State for Cystadenocarcinoma of Pancreas? Amnon Gotian, M.D., and Seymour Katz, M.D., F.A.C.G., F.A.C.P. Department of Medicine, North Shore University Hospital, Manhasset, New York; and New York University School of Medicine, New York, New York
ABSTRACT We report a 74-yr-old woman with Crohn’s disease and acute pancreatitis who, 3 yr after resolution of the latter, developed cystadenocarcinoma of the pancreas. No drug, toxin, or other etiologies including contiguous duodenal involvement were identified as responsible for the pancreatitis, suggesting that pancreatitis was an extraintestinal manifestation of her Crohn’s disease. Could Crohn’s-associated pancreatitis be a premalignant state for cystadenocarcinoma of the pancreas? (Am J Gastroenterol 1999;94: 2301–2302. © 1999 by Am. Coll. of Gastroenterology)
INTRODUCTION The association between pancreatitis and Crohn’s disease has been increasingly recognized (1–3). In several studies, pancreatitis as an extraluminal manifestation of Crohn’s disease itself was the only explanation. We report the first case of Crohn’s-related pancreatitis without contiguous duodenal involvement and with subsequent development of cystadenocarcinoma of the pancreas.
Brief Case Reports
2301
In March 1988 she was readmitted for anemia, weakness, and fatigue. Biopsies of colonic mucosa were negative for inflammation. Subsequent CT of the abdomen and pelvis demonstrated a thickened wall and narrowed lumen of the terminal ileum consistent with inflammatory bowel disease. A small focal abnormality was found in the liver consistent with a small hemangioma. The pancreas was normal. In June 1988, the patient underwent a resection of 31 cm of the terminal ileum with a 5-cm-long segment of attached cecum because of persistent debility. The pathology report described extensive ulcerations and pseudopolyp formation with a small fistula into the mesentery. A follow-up small bowel series in October 1989 showed no evidence of recurrence. A colonoscopy performed in July 1991 revealed normal colonic mucosa. The patient remained asymptomatic and off all medications. In March of 1994, while not taking any medications, the patient developed abdominal pain and underwent ultrasonography of the abdomen. A focal lesion on right lobe of liver was found to be consistent with small hemangioma and dilatation of the pancreatic duct with no discrete mass in the pancreas. The pancreatic body was slightly heterogeneous, consistent with pancreatitis. Her amylase level was 1188 (24 –97 normal), her white blood cells 13,600 with 90% polymorphonuclears, hemoglobin 12.7, hematocrit 38.0, and platelets 231. Serum amylase fell to 346 (normal 34 – 122), lipase 130 (normal ⬍ 60), total bilirubin 0.8, albumin 3.3, alkaline phosphatase 58, AST 18, ALT 18, CPK 45, LDH 154, and calcium 8.8. A computed tomography scan of the abdomen and pelvis was consistent with the clinical history of pancreatitis. No biliary tract stones or disease were identified. A suggestion of possible duodenal wall thickening was believed to be secondary to the surrounding peripancreatic inflammation. The pancreatitis resolved shortly afterward, and the patient was discharged 6 days later with an amylase level of 44. The patient continued to remain asymptomatic with normal amylase levels until June 1997, when she noted weight loss and
CASE REPORT A 74-yr-old white woman of Hungarian descent was admitted in 1987 to the hospital with intermittent melena and black stool. Her past medical history included mitral valve prolapse, uterine prolapse, chronic urinary tract infections, bilateral carotid disease, and bilateral subtotal thyroidectomy for benign nodules, and 15 years of “irritable bowel syndrome.” Esophagogastroscopy, sigmoidoscopy, and subsequent colonoscopy were all negative. Enteroclysis showed extensive ileitis, ulcerations, and pseudopolyposis consistent with Crohn’s disease.
Figure 1. CT scan of abdomen demonstrating 6 ⫻ 3-cm mass on the head of the pancreas.
2302
Brief Case Reports
altered bowel movements. A large cystic, necrotic appearing mass 6 ⫻ 3 cm was found on the head of the pancreas on computed tomography of the abdomen (Fig. 1). The mass appeared to communicate with both distal common bile duct and pancreatic duct consistent with a neoplasm of the pancreas. A subsequent magnetic resonant cholangiogram and angiogram revealed vessels free of tumor, but tumor was encroaching the portal vein. There was no evidence of distant metastasis. In July 1997 the patient underwent pancreatoduodenectomy with resection of the duodenum and head of pancreas. A multicystic mucinous adenocarcinoma and cystadenoma largely replaced the head of the pancreas. The tumor was found extending into the wall of the duodenum and ampullary region, causing mucosal ulceration with a duodenal ampullary fistula. There was no gross evidence of Crohn’s disease in the residual bowel at time of surgery. Ten lymph nodes and the resected margins were free of tumor. The patient was discharged on a low fat diet with a jejunostomy for supplemental feeding. The latter was subsequently discontinued and she has fared well for 1.5 years of observation.
DISCUSSION An increase in reported cases of pancreatitis in patients with Crohn’s disease has been highly suggestive of their association (1–3). In many cases, no etiological factors were found except for Crohn’s disease itself, indicating pancreatitis as an extraintestinal complication of Crohn’s. In 1950, Ball et al. (4) were the first to suggest the association between pancreatitis and inflammatory bowel disease. Pancreatitis associated with inflammatory bowel disease is most often ascribed to biliary tract disease and to medications such as azathioprine, 6-mercaptopurine, corticosteroids, 5-aminosalicyclic acid, sulfasalazine, metronidazole, and intravenous lipid emulsions (5). Gschwantler et al. (6) described a patient with granulomatous inflammation caused by Crohn’s disease. The involved areas included the stomach, duodenum, and the head of the pancreas, suggesting contiguous pancreatic involvement of Crohn’s disease. Subsequently, cases of pancreatitis with duodenal involvement of Crohn’s disease, excluding other etiologies, were reported (7, 8). Pancreatitis without Crohn’s involvement of the duodenum, drugs, or other known etiological factors suggests its role as an extraintestinal manifestation of Crohn’s disease (7). Although pancreatic cancer associated with pancreatitis is well described, it has always been described in a setting of chronic pancreatitis (9). We present an unusual case of Crohn’s disease with acute pancreatitis with complete resolution, then, after 3 yr, the development of pancreatic cancer. Our patient lacked a history of biliary tract disease, drug exposure, or contiguous Crohn’s disease involving the duodenum. The head of the pancreas was replaced with
AJG – Vol. 94, No. 8, 1999
multicystic mucinous adenocarcinoma. Could Crohn’s-associated pancreatitis be a premalignant state for cystadenocarcinoma of the pancreas? Reprint requests and correspondence: Seymour Katz, M.D., F.A.C.P., F.A.C.G., 1000 Northern Boulevard, Great Neck, NY 11021. Received Apr. 6, 1998; accepted Jan. 27, 1999.
REFERENCES 1. Meyers S, Greenspan J, Greenstein AJ, et al. Pancreatitis coincident with Crohn’s ileocolitis. Report of a case and a review of the literature. Dis Colon Rectum 1987;30:119 –22. 2. Matsumoto T, Matusi T, Iida M, et al. Acute pancreatitis as a complication of Crohn’s disease. Am J Gastroenterol 1989;84: 804 –7. 3. Niemela S, Lehtola J, Karrtunen T, et al. Pancreatitis in patients with chronic inflammatory bowel disease. Hepatogastroenterology 1989;36:175–7. 4. Ball PW, Baggenstoss AH, Bargen JA. Pancreatic lesions associated with chronic ulcerative colitis. Arch Pathol 1950;50:347–58. 5. Weber P, Seibold F, Jenss H. Acute pancreatitis in Crohn’s disease. J Clin Gastroenterol 1993;17:286 –91. 6. Gschwantler M, Kogelbauer G, Klose W, et al. The pancreas as a site of granulomatous inflammation in Crohn’s disease. Gastroenterology 1995;108:1246 –9. 7. Eisner TS, Goldman IS, McKinley MJ. Crohn’s disease and pancreatitis. Am J Gastroenterol 1993;88:583– 6. 8. Legge DA, Carlson HC, Judd ES. Roentgenologic features of regional enteritis of the upper gastrointestinal tract. Am J Roentgenol Radium Ther Nucl Med 1970;110:355– 60. 9. Ho HS, Frey CF. Current approach to the surgical management of chronic pancreatitis. Gastroenterologist 1997;5:128 –36.
Amitriptyline Absorption in a Patient With Short Bowel Syndrome Brett Robbins, M.D., and Robert A. Reiss, Pharm. D., B.C.P.S. Departments of Medicine and Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester; Department of Medicine and Pediatrics, and Department of Pharmacy Practice, ViaHealth, Rochester General Hospital, Rochester, New York
ABSTRACT Oral drug therapy in patients with short bowel syndrome can be quite challenging. We report the case of a 40-yr-old woman with short bowel syndrome and depression requiring antidepressant drug therapy. After buccal administration of amitriptyline, therapeutic serum antidepressant concentrations were attained despite the patient having only 18 inches of proximal small bowel. Clinical improvement in mood was seen, with the only drug side effects being dry mouth and bitter drug taste. Buccal absorption likely is playing a major role in attaining therapeutic serum tricyclic antidepressants drug concentrations. (Am J Gastroenterol 1999;94:2302–2304. © 1999 by Am. Coll. of Gastroenterology)