Madisch A, Wiedbrauck F, Marquard F, Stolte M, Hotz J
Klinik für Gastroenterologie, Allgemeines Krankenhaus Celle, Germany.
Z Gastroenterol. 2002 Feb;40(2):59-66. doi: 10.1055/s-2002-20209.
At increasing use of high-dose 5-fluorouracil-based chemotherapy for metastatic colorectal and gastric cancer complicated drug-induced colitis is observed more frequently. From May 1998 to November 2000 we observed 6 cases of 5-fluorouracil-induced colitis, in which we looked for involvement of small intestine. We report summing up on the 6 cases including both endoscopic and histological findings in both sites of the gut.
In 2 men and 4 women (age 49-78 years) with advanced colon (n = 2), gastric (n = 3 ) and gallbladder (n = 1) cancer a palliative weekly high-dose infusional 5-fluorouracil (2,6 g/m(2)/24 h) and folinic acid (500 mg/m(2)/2 h) chemotherapy was performed. Few days after 1-5 chemotherapy courses the patients were admitted to our hospital with abdominal pain and partly severe watery diarrhea (up to 20 times evacuations/per day). The stool cultures were negative and there were no proof both of clostridium difficile and his toxin A and B. In 4 patients colonoscopy showed different grades of colitis up to diffuse erythema and microlesions, 2 patients had no visible lesions. In 4 patients endoscopy of the upper GI-tract showed a severe inflammation (n = 1) and a fibrinopurulent exsudate, severe edema and isolated ulcerations (n = 3) of jejunum after gastrectomy or duodenum with intact stomach. In the histological assessment different grades of 5-FU-induced colitis without (n = 2) or with (n = 4) involvement of the upper small intestine destruction of the superficial mucosa and crypts (epitheliumapoptosis) were found. 5 patients were treated by antibiotics (vancomycin n = 2, metronidazole n = 3), glucocorticoids (n = 5) and Saccaromyces cerevisiae (n = 3). After 8-10 days the patients were complete free of symptoms. One patient died due to the enterocolitis.
The present cases demonstrate that high-dose 5-fluorouracil-based chemotherapy not only induces a colitis but also may involve the upper small intestine tract. Consequently, it represents an increasing and serious adverse event of high-dose chemotherapy. The etiology of the enterocolitis (drug- or bacterial-induced) needs further investigations in order to find a causal therapy and/or prophylaxis.
随着高剂量基于5-氟尿嘧啶的化疗在转移性结直肠癌和胃癌治疗中的应用增加，药物性结肠炎的发生率也更为常见。1998年5月至2000年11月期间，我们观察到6例5-氟尿嘧啶诱导的结肠炎病例，在此过程中我们探寻了小肠受累情况。我们现总结这6例病例，涵盖肠道两个部位的内镜及组织学检查结果。
2例男性和4例女性（年龄49 - 78岁），分别患有晚期结肠癌（2例）、胃癌（3例）和胆囊癌（1例），接受了每周一次的姑息性高剂量5-氟尿嘧啶（2.6 g/m²/24小时）和亚叶酸（500 mg/m²/2小时）静脉化疗。在1 - 5个化疗疗程后的数天，患者因腹痛和部分严重水样腹泻（每日排便多达20次）入住我院。粪便培养结果为阴性，未检测到艰难梭菌及其毒素A和B。4例患者的结肠镜检查显示不同程度的结肠炎，直至弥漫性红斑和微小病变，2例患者未见明显病变。4例患者的上消化道内镜检查显示，1例有严重炎症，3例在胃切除术后空肠或十二指肠（胃完整）出现纤维蛋白脓性渗出物、严重水肿及孤立性溃疡。组织学评估发现不同程度的5-氟尿嘧啶诱导的结肠炎，其中2例不累及上小肠，4例累及，表现为浅表黏膜和隐窝破坏（上皮细胞凋亡）。5例患者接受了抗生素治疗（2例使用万古霉素，3例使用甲硝唑）、糖皮质激素治疗（5例）和酿酒酵母治疗（3例）。8 - 10天后，患者症状完全消失。1例患者因小肠结肠炎死亡。
目前的病例表明，高剂量基于5-氟尿嘧啶的化疗不仅会引发结肠炎，还可能累及上小肠。因此，这是高剂量化疗中日益严重的不良事件。小肠结肠炎的病因（药物性或细菌性）需要进一步研究，以便找到针对性的治疗方法和/或预防措施。
