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Small-Cell Cancers, and an Unusual Reaction to Chemotherapy

CASE 4. FLUOROURACIL-RELATED SMALL BOWEL VASCULITIS

Geisinger Medical Center, Danville, PA

Fluorouracil (FU) is one of the most commonly used chemotherapeutic agents in clinical oncology practice, alone or in differentcombinations. In colorectal cancer the addition of leucovorin (LV) to FU resulted in improved patient survival, improved objectivetumor response, and better quality of life.¹ We report a case of ischemic small-bowel injury in a patient who received adjuvantchemotherapy with oxaliplatin (OP), FU, and LV and was found to have angiographic evidence of vasculitis in the superiormesenteric artery (SMA) territory. This will add to the series of patients reported with FU-related or FU-induced vascular injury tothe small bowel.²

A 73-year-old male underwent a left hemicolectomy for stage III colon cancer. He was enrolled in an adjuvant chemotherapyresearch protocol consisting of FU 500 mg/m² intravenous (IV) weekly boluses, each administered during 1 hour; LV 500 mg/m²IV weekly infusions, each administered during 2 hours; and OP 85 mg/m² IV infusions every 2 weeks for 6 weeks, followed by 2weeks of rest. After the third cycle of FU, LV, and OP, he presented with weakness, diarrhea, abdominal cramps, and poor appetite.His abdomen was distended and he had heme-positive stools. Stool cultures and Clostridium difficile toxin antigen were negative.He was not neutropenic. Colonoscopy revealed dusky edematous changes in the ascending colon and focal ulceration with patchysubmucosal hemorrhages in the distal ileum (Figs 1 and 2, arrows). Biopsies of the colon mucosa showed densely neutrophilicinfiltrates of the lining epithelium and associated mild focal cryptitis. An SMA angiogram was performed and it revealed beadingin ileal branches, consistent with the ischemic territory (Fig 3). Vasculitis serologies were negative. The patient was treatedconservatively with hydration and IV antibiotics, and he was later rechallenged with a 20% reduction of FU dose, with no recurrenceof his symptoms in long-term follow-up.

View larger version (150K): [in this window] [in a new window]   Fig 1. Distal ileum endoscopy. Superficial mucosal erosions and ulcerations arrow).

View larger version (160K): [in this window] [in a new window]   Fig 2. Dusky edematous changes in the ascending colon giving the appearance of ischemic colitis (arrow).

View larger version (201K): [in this window] [in a new window]   Fig 3. Superior mesentery artery angiogram showing a beading appearance of ileal branches (arrow).

A series of patients with resected adenocarcinoma of colon who were treated with FU and LV and developed severe erosions andsuperficial ulcerations in the ileum has been described.² These patients were successfully rechallenged with a 20% reduction of FUdose without further toxicities. The mechanisms involved are thought to be multifactorial, including alteration of local mucosal bloodflow^4,6 and thrombogenic⁷ and vasospastic^3,8 effects of FU on the vascular epithelium. Indeed, Mosseri et al⁸ demonstrated in vitrothat FU causes direct endothelial-independent vasoconstriction related to activation of protein kinase C.

Our patient had superficial erosions and ulcerations in the ileum (Fig 3) as well as ischemic appearance of the colon. The characteristic findings of beading on the angiogram suggest an underlying ischemic mechanism related to FU-based therapy.

REFERENCES

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Fata F, Ron IG, Kemeny N, et al: 5-Fluorouracil-induced small bowel toxicity in patients with colorectal carcinoma. Cancer 86:1129–1134, 1999[CrossRef][Medline]

Gradishar WJ, Vokes EE: 5-Fluorouracil cardiotoxicity: A critical review. Ann Oncol 1:409–414, 1990[Abstract/Free Full Text]

Narsete Th, Ansfield F, Wirtanen G, et al: Gastric ulceration in patients receiving intrahepatic infusion of 5-fluorouracil. Ann Surg 186:734–737, 1977[Medline]

Suda K, Seki T, Kano Y, et al: Continuous 5-fluorouracil infusion acute causing gastric mucosal lesions. Endoscopy25:426–427, 1993[Medline]

Kakinuma S, Ohwada S: Gastric mucosal blood flow and gastric secretion following intravenous administration of 5-fluorouracil in rats. Cancer Chemother Pharmacol 39:357–360, 1997[CrossRef][Medline]

Kuzel T, Esparaz B, Green D, et al: Thrombogenicity of intravenous 5-fluorouracil alone or in combination with cisplatin. Cancer 65:885–889, 1990[CrossRef][Medline]

Mosseri M, Fingert HJ, Vartikosski L, et al: In vitro evidence that myocardial ischemia resulting from 5-fluorouracil chemotherapy is due to protein kinase c-mediated vasoconstriction of vascular smooth muscle. Cancer Res 53:3028–3033, 1993[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bucaloiu, I. D. Articles by Fata, F. Search for Related Content PubMed PubMed Citation Articles by Bucaloiu, I. D. Articles by Fata, F. Social Bookmarking                            What's this?