Zusammenfassung
Hintergrund: Zur palliativen Behandlung metastasierter kolorektaler und Magenkarzinome werden zunehmend 5-Fluorouracil-24-h-Hochdosischemotherapie-Schemata (HD-5-FU) eingesetzt. Hierbei werden gehäuft persistierende Durchfälle und abdominelle Schmerzen beobachtet. Als Ursache wird eine 5-FU-assoziierte Kolitisform angenommen, die bisher nicht ausreichend charakterisiert ist. Hier werden 6 Fälle einer 5-Fluorouracil-induzierten Kolitis dokumentiert und auf eine mögliche Beteiligung des Dünndarms anhand von endoskopischen und histologischen Untersuchungen des Dünn- und Dickdarms untersucht.
Fallsammlung: 2 Männer und 4 Frauen zwischen 49 und 62 Jahren erhielten im Rahmen metastasierter Kolon- (n = 2) Magen- (n = 3)- bzw. Gallengangskarzinome (n = 1) eine palliative wöchentliche Chemotherapie mit 5-Fluorouracil (2600 mg/m2/24 h)/Folinsäure (500 mg/m2/2 h). Zwischen der 1. und 5. Applikation der Chemotherapie stellten sich die Patienten mit z. T. heftigsten wässrigen Durchfällen (bis zu 20-mal/Tag) außerplanmäßig vor (WHO-Klassifikation Stadium Grad III). Die Stuhlkulturen waren bei allen Patienten negativ einschließlich des fehlenden Nachweises von Clostridium difficile und seinen Toxinen A und B. Die bei der Koloskopie erhobenen Befunde reichten von unauffälliger Schleimhaut (n = 2) bis zu kolitischen Veränderungen mit hochrotem Ödem, verstärkten Fibrinausschwitzungen sowie Mikroulzerationen (n = 4). Bei 4 Patienten war zusätzlich zum Kolon auch der obere Dünndarm mit endoskopisch imponierendem Erythem (n = 1) oder schmierigen Belägen und Ulzerationen (n = 3). befallen. In der histologischen Aufarbeitung zeigte sich eine unterschiedlich ausgeprägte apoptotische Destruktion der Krypten, bei Dünndarmbefall partiell Zottenatrophie und minimale apikale Erosionen. Unter der Therapie mit Antibiotika (Vancomycin [n = 2] , Metronidazol [n = 3]) Glukokortikoiden (n = 5) und/oder dem Hefepräparat Saccaromyces cerevisiae (n = 3) waren 5 Patienten innerhalb von 8-10 Tagen beschwerdefrei. Eine Patientin verstarb an den Folgen der Enterokolitis.
Schlussfolgerung: Diese Fallsammlung zeigt, dass 5-Fluoruracil nicht nur eine histologisch nachweisbare Kolitis induzieren, sondern auch das gesamte Intestinum erfassen kann. Die oft schweren, persistierenden Verlaufsformen stellen eine seltene, aber ernst zu nehmende Komplikation dar. Die Genese der Kolitis (medikamententoxisch und/oder bakteriell) mit dem Ziel einer gezielten Therapie und/oder Prophylaxe muss weiter untersucht werden.
5-fluorouracil-induced colitis-A review based upon consideration of 6 cases
Background: At increasing use of high-dose 5-fluorouracil-based chemotherapy for metastatic colorectal and gastric cancer complicated drug-induced colitis is being 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.
Case reports: 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/m2/24 h) and folinic acid (500 mg/m2/2 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.
Conclusions: 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.
Schlüsselwörter
5-Fluorouracil - 5-FU - Hochdosischemotherapien - Kolitis
Key words
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Korrespondenzadresse
Dr. med. Ahmed Madisch
Abteilung für Gastroenterologie
Allgemeines Krankenhaus Celle
Siemensplatz 4
29223 Celle
eMail: gastroenterologie@akh-celle.de
