altered bowel movements. A large cystic, necrotic appearingmass 63 3 cm was found on the head of the pancreas oncomputed tomography of the abdomen (Fig. 1). The massappeared to communicate with both distal common bile ductand pancreatic duct consistent with a neoplasm of the pan-creas. A subsequent magnetic resonant cholangiogram andangiogram revealed vessels free of tumor, but tumor wasencroaching the portal vein. There was no evidence ofdistant metastasis.

In July 1997 the patient underwent pancreatoduodenec-tomy with resection of the duodenum and head of pancreas.A multicystic mucinous adenocarcinoma and cystadenomalargely replaced the head of the pancreas. The tumor wasfound extending into the wall of the duodenum and ampul-lary region, causing mucosal ulceration with a duodenalampullary fistula. There was no gross evidence of Crohn’sdisease in the residual bowel at time of surgery. Ten lymphnodes and the resected margins were free of tumor. Thepatient was discharged on a low fat diet with a jejunos-tomy for supplemental feeding. The latter was subse-quently discontinued and she has fared well for 1.5 yearsof observation.

DISCUSSION

An increase in reported cases of pancreatitis in patients withCrohn’s disease has been highly suggestive of their associ-ation (1–3). In many cases, no etiological factors were foundexcept for Crohn’s disease itself, indicating pancreatitis asan extraintestinal complication of Crohn’s.

In 1950, Ball et al. (4) were the first to suggest theassociation between pancreatitis and inflammatory boweldisease. Pancreatitis associated with inflammatory boweldisease is most often ascribed to biliary tract disease and tomedications such as azathioprine, 6-mercaptopurine, corti-costeroids, 5-aminosalicyclic acid, sulfasalazine, metronida-zole, and intravenous lipid emulsions (5).

Gschwantleret al. (6) described a patient with granulo-matous inflammation caused by Crohn’s disease. The in-volved areas included the stomach, duodenum, and the headof the pancreas, suggesting contiguous pancreatic involve-ment of Crohn’s disease. Subsequently, cases of pancreatitiswith duodenal involvement of Crohn’s disease, excludingother etiologies, were reported (7, 8).

Pancreatitis without Crohn’s involvement of the duode-num, drugs, or other known etiological factors suggests itsrole as an extraintestinal manifestation of Crohn’s disease(7).

Although pancreatic cancer associated with pancreatitis iswell described, it has always been described in a setting ofchronic pancreatitis (9). We present an unusual case ofCrohn’s disease with acute pancreatitis with complete res-olution, then, after 3 yr, the development of pancreaticcancer. Our patient lacked a history of biliary tract disease,drug exposure, or contiguous Crohn’s disease involving theduodenum. The head of the pancreas was replaced with

multicystic mucinous adenocarcinoma. Could Crohn’s-as-sociated pancreatitis be a premalignant state for cystadeno-carcinoma of the pancreas?

Reprint requests and correspondence:Seymour Katz, M.D.,F.A.C.P., F.A.C.G., 1000 Northern Boulevard, Great Neck, NY11021.

Received Apr. 6, 1998; accepted Jan. 27, 1999.

REFERENCES

1. Meyers S, Greenspan J, Greenstein AJ, et al. Pancreatitis co-incident with Crohn’s ileocolitis. Report of a case and a reviewof the literature. Dis Colon Rectum 1987;30:119–22.

2. Matsumoto T, Matusi T, Iida M, et al. Acute pancreatitis as acomplication of Crohn’s disease. Am J Gastroenterol 1989;84:804–7.

3. Niemela S, Lehtola J, Karrtunen T, et al. Pancreatitis in patientswith chronic inflammatory bowel disease. Hepatogastroenter-ology 1989;36:175–7.

4. Ball PW, Baggenstoss AH, Bargen JA. Pancreatic lesions associ-ated with chronic ulcerative colitis. Arch Pathol 1950;50:347–58.

5. Weber P, Seibold F, Jenss H. Acute pancreatitis in Crohn’sdisease. J Clin Gastroenterol 1993;17:286–91.

6. Gschwantler M, Kogelbauer G, Klose W, et al. The pancreas asa site of granulomatous inflammation in Crohn’s disease. Gas-troenterology 1995;108:1246–9.

7. Eisner TS, Goldman IS, McKinley MJ. Crohn’s disease andpancreatitis. Am J Gastroenterol 1993;88:583–6.

8. Legge DA, Carlson HC, Judd ES. Roentgenologic features ofregional enteritis of the upper gastrointestinal tract. Am JRoentgenol Radium Ther Nucl Med 1970;110:355–60.

9. Ho HS, Frey CF. Current approach to the surgical managementof chronic pancreatitis. Gastroenterologist 1997;5:128–36.

Amitriptyline Absorption in aPatient With Short Bowel SyndromeBrett Robbins, M.D., and Robert A. Reiss, Pharm. D., B.C.P.S.Departments of Medicine and Pediatrics, University ofRochester School of Medicine and Dentistry, Rochester;Department of Medicine and Pediatrics, and Department ofPharmacy Practice, ViaHealth, Rochester General Hospital,Rochester, New York

ABSTRACTOral drug therapy in patients with short bowel syndrome canbe quite challenging. We report the case of a 40-yr-oldwoman with short bowel syndrome and depression requiringantidepressant drug therapy. After buccal administration ofamitriptyline, therapeutic serum antidepressant concentra-tions were attained despite the patient having only 18inches of proximal small bowel. Clinical improvement inmood was seen, with the only drug side effects being drymouth and bitter drug taste. Buccal absorption likely isplaying a major role in attaining therapeutic serum tricy-clic antidepressants drug concentrations. (Am J Gastro-enterol 1999;94:2302–2304. © 1999 by Am. Coll. ofGastroenterology)

2302 Brief Case Reports AJG – Vol. 94, No. 8, 1999

INTRODUCTION

Short bowel syndrome (SBS) is a chronic and debilitatingdisease. The most common causes in adults are Crohn’sdisease, mesenteric infarction, and radiation enteritis, butthere are a host of miscellaneous other causes. The mostcommon treatment of SBS is total parenteral nutrition(TPN), but this has been reported to lead to a host ofpsychological problems. The literature addressing the psy-chological problems of patients with SBS requiring perma-nent TPN is limited (1–4). There are many reasons forpatients with SBS on TPN to be depressed. These includeloss of normal body function, loss of independence, alteredbody appearance, and dependence upon medical supplies.As high as 22% of patients needing permanent TPN havebeen reported to show depressive signs and symptoms (4). Thisestimate is much higher than the prevalence of major depres-sive disorder in the general population, about 3–5% (5).

Drug therapy in SBS can be complicated by inadequateabsorption of oral drugs in the small intestine due to loss ofeffective surface area (6). Many medications are availableonly as oral dosage forms, which greatly limits therapychoices. Several published reports suggest tricyclic antide-pressants may be absorbed by buccal or sublingual admin-istration (7). A case of treating a depressed patient with SBSon long term TPN using amitriptyline is described.

CASE REPORT

E.G. is a 40-yr-old woman who was diagnosed with Crohn’sdisease at age 18 yr. She has suffered multiple admissionsand operations for this disorder, including toxic megacolonand strictures. After several years and multiple operations,she has been left with approximately 18 inches of proximalsmall intestine. For the past 8 yr she has been dependentupon TPN for all of her caloric and fluid needs. Because ofthe nature of her illness, she suffers chronic dysthymia andepigastric pain. She has been admitted to the hospital mul-tiple times for exacerbation of her ill defined epigastric pain.In 1995 she spent approximately 300 days in the hospital.She had sleep disturbance, difficulty concentrating, psy-chomotor activation, and increased appetite. She had occa-sional tearful episodes, an overall feeling of worthlessnessand helplessness, and did feel depressed. She attempted toend her life once by stopping her TPN. For these reasons, wewished to begin an antidepressant medication in addition tocounseling. However, her SBS made the route of adminis-tration a problem. The depressed patient’s response to drugtherapy is difficult to quantify, especially if medicationabsorption may be a problem.

In November 1996, a search of the literature revealed noreports suggesting an antidepressant of choice in this patientpopulation. Tricyclic antidepressants have been reported tohave buccal absorption and are also easily measured in theserum. Therefore, we started amitriptyline 25 mg at bedtimeand titrated up to a dose of 125 mg. The patient was

instructed to crush the tablets and to let the powder remainin her mouth to dissolve to minimize the possibility ofswallowing part of the dose. Because of initial noncompli-ance on the part of the patient, the initial serum combinedamitriptyline and nortriptyline concentration (ANC) was,20 ng/ml (usual therapeutic range 100–250 ng/ml) (8).After a discussion of the importance of medication compli-ance, E.G. began to take her medication consistently and herANC rose to 147 ng/ml. In March 1997, the ANC was 677ng/ml, necessitating overnight cardiac monitoring and dosereduction to 75 mg. We believe that the toxic level was dueto continued liver dysfunction (bilirubin 4.6 mg/dl, ALT394 mU/ml, albumin 4.0 g/dl, AST 311 mU/ml, alkalinephosphatase 248 mU/ml) from chronic TPN and perhapsconfusion on her part in taking the medication. We havemonitored her ANC monthly and it has remained in thetherapeutic range on 75 mg/day (Table 1).

E.G.’s dysthymia has subjectively improved and she nowsuffers far fewer bouts of the ill defined epigastric pain. Shefeels less depressed and more relaxed, has almost no cryingspells, and has more confidence in herself. She has evenbegun to think about the possibility of a liver/small boweltransplant. She was admitted to the hospital a total of 8 wkin the past 12 months, mainly because of infectious com-plications of heri.v. access.

DISCUSSION

Amitriptyline is extensively absorbed through the stomachand small intestine (8). It has an average half life of 15 h, ishepatically metabolized by N-demethylation and hydroxy-lation, and has an active metabolite, nortriptyline (9). Theusual adult daily dosage ranges between 50 and 300 mg/day.We chose to treat E.G.’s chronic dysthymia with amitrip-tyline because of its proven efficacy for depression, ex-pected buccal absorption, and the ability to follow serumlevels to confirm absorption.

Table 1. Time Course of Tricyclic Antidepressant Dosage,Serum Concentration, and Serum Bilirubin

Date

AmitriptylineDosage(mg)

ANC(ng/ml)*

Serum TotalBilirubin

Concentration(mg/dl)

Nov 1996 25 ,20 0.7Dec 1996 100 147 0.5Feb 1997 100 677 4.3Mar 1997 50 264 5.5Apr 1997 25 47 4.6May 1997 75 223 4.4June 1997 75 170 3.3July 1997 75 135 2.5Oct 1997 75 127 3.2Jan 1998 75 53 3.5Apr 1998 75 124 2.7May 1998 75 108 6.3Aug 1998 50 208 11.2

* Serum combined amitriptyline and nortriptyline concentration.

2303AJG – August, 1999 Brief Case Reports

E.G. demonstrates good absorption of amitriptyline aftercrushing her dose and allowing the powder to dissolve in hermouth. This might be explained by the overwhelming li-pophilicity of amitriptyline and the large absorptive surfacearea of the mouth. Also, absorption of amitriptyline fromswallowing could still be expected from the 18 inches ofproximal small intestine and reduced first pass metabolismbecause of E.G.’s impaired liver function. Most importantly,E.G. responded clinically with the only side effects beingdry mouth and a slightly bitter taste while the amitriptylinepowder was in her mouth. We believe that this case illus-trates the potential use of oral tricyclic antidepressants,particularly amitriptyline, in the management of depressionin patients with SBS and unreliable oral absorption.

Reprint requests and correspondence:Brett Robbins, M.D.,Departments of Medicine and Pediatrics, ViaHealth, Rochester Gen-eral Hospital, 1425 Portland Avenue, Rochester, NY 14621-3095.

Received Sep. 24, 1998; accepted Jan. 27, 1999.

REFERENCES

1. Gilchrist PN, Phillips PJ, et al. Dietary compliance in the shortbowel syndrome. J Parenter Enter Nutr 1984;3:315–6.

2. Price BS, Levine EL. Permanent total parenteral nutrition: Psy-chologic and social responses of the early stages. J ParenterEnter Nutr 1979;3:48–52.

3. MacRitchie KJ. Life without eating or drinking. Can PsychiatryAssoc J 1978;23:373–8.

4. Gullege AD, Gipson WT, Steiger E, et al. Home parenteralnutrition for the short bowel syndrome. Gen Hosp Psychiatry1980;2:271–80.

5. Myers JK, Weissman MM, Tischler GE, et al. Six monthprevalence of psychiatric disorders in three communities. ArchGen Psychiatry 1984;41:959–70.

6. McFadden MA, DeLegge MH, Kirby DF. Medication delivery inthe short-bowel syndrome. J Parenter Enteral Nutr 1993;17:180–6.

7. Gibaldi M. Nonoral medication In: Biopharmaceutics and clin-ical pharmacokinetics, 4th ed. Malvern: Lea and Febiger; 1991:80–123.

8. DeVane CL. Cyclic antidepressants. In: Evans WE, Schentag JJ,Jusko, WJ, et al., eds. Applied pharmacokinetics: Principles oftherapeutic drug monitoring, 3rd ed. Vancouver: Applied Thera-peutics, 1992:33:1–33;47.

9. Amitriptyline package insert; Zeneca Pharmaceuticals, Wil-mington, DE.

Mesalamine-AssociatedThrombocytopeniaRichard J. Farrell, M.D., M.R.C.P.I.,Mark A. Peppercorn, M.D., F.A.C.G., Steven N. Fine, M.D.,and Pierre Michetti, M.D.Department of Gastroenterology, Beth Israel Deaconess MedicalCenter, Harvard Medical School, Boston, Massachusetts

ABSTRACTWe describe a case of a 25-yr-old woman with ulcerativecolitis who developed marked thrombocytopenia during

treatment and upon rechallenge with oral mesalamine. Incontrast to its parent drug, sulfasalazine, which has oftenbeen reported to cause serious blood disorders, particularlyagranulocytosis, mesalamine has rately been implicated as acause of serious blood disorders. Although previous cases ofhematological toxicity have been described in patients tak-ing mesalamine, none of these patients were rechallenged inan effort to prove causality between 5-aminosalicyclic acidand the hematological abnormality as well as outrule thepossible “autoimmune” contribution of inflammatory boweldisease to the hematological toxicity of these agents. Thisreport demonstrates that mesalamine has the potential, likesulphasalazine, to cause marked thrombocytopenia in anidiosyncratic fashion. All patients receiving mesalaminetherapy, either orally or topically should have regular, com-plete blood profiles. (Am J Gastroenterol 1999;94:2304–2306. © 1999 by Am. Coll. of Gastroenterology)

INTRODUCTION

Mesalamine (5-aminosalicyclic acid) is indicated for mild tomoderate exacerbations of inflammatory bowel disease(IBD) and as an agent to maintain remission. In contrast toits parent drug, sulfasalazine, which has often been reportedto cause serious blood disorders, particularly agranulocyto-sis (1), mesalamine has rarely been implicated as a cause ofserious blood disorders (2). Although sulfasalazine-associ-ated thrombocytopenia has been well documented in arthri-tis and inflammatory bowel disease patients (3, 4), therehave been only two previous cases of thrombocytopeniareported in patients taking mesalamine (5, 6). Althoughthese observations clearly suggest the possibility of a directrelationship between administration of the agent and hema-tological toxicity, neither of these patients were rechal-lenged. For this reason, we report a patient who experiencedmarked thrombocytopenia during treatment and upon re-challenge with oral mesalamine.

CASE REPORT

A 25-yr-old woman presented with rectal bleeding, diarrhea,and abdominal pain in 1995. On colonoscopic examination,findings consistent with extensive ulcerative colitis werefound. A small bowel follow-through was normal. Routinebiochemical tests, including hematocrit, hemoglobin con-centration, leucocytes, platelet counts, BUN, creatinine, andprothrombin time, were normal. She was begun on oralmesalamine (Asacol) tablets, 4.8 g daily, and went intoremission. She gave no prior history of drug allergies. After3 months, her mesalamine dosage was tapered to 2.4 g daily,and she remained in remission on this dosage over the next2 yr.

In December 1997, she experienced a flare in her colitis.Her mesalamine was increased to 4.8 g daily and ciprofloxa-cin 500 mgb.i.d. was added for 1 month. At that time, herplatelet count was 225,000 cm3. In early March, she noted

2304 Brief Case Reports AJG – Vol. 94, No. 8, 1999