Chirurgisches Management der perforationsbedingten Peritonitis im Zusammenhang mit einer Bevacizumab-Therapie

Zusammenfassung

Hintergrund: Bevacizumab (Avastin®, Fa. Roche, Genentech) ist der erste Angiogeneseinhibitor, der für die routinemäßige klinische Behandlung maligner Tumoren zugelassen wurde. Das Nebenwirkungsprofil des Antikörpers (Ak) unterscheidet sich von jenem der traditionellen Chemotherapie. Eine zwar seltene, aber schwerwiegende Avastin®-spezifische Komplikation ist die gastrointestinale (GI) Perforation. Sie geht mit einer hohen Morbidität und Letalität einher. Das Ziel der vorliegenden Arbeit bestand darin, anhand eigener und publizierter Erfahrungen befundbezogene Besonderheiten dieser außergewöhnlichen Pathogenese einer perforationsbedingten Peritonitis einschließlich therapeutischem „Outcome“ darzustellen. Methodik: Es wurden die Daten von Patienten mit einer bevacizumabinduzierten perforationsbedingten Peritonitis seit klinischer Einführung i) aus der eigenen Patientenklientel prospektiv erfasst, ii) Literaturangaben gegenübergestellt (historische Vergleichsgruppe) und iii) hinsichtlich der Ergebnisse des chirurgischen Managements (Zielparameter: Raten von Anastomoseninsuffizienzen / Wundheilungsstörungen, Morbidität, Letalität) ausgewertet. Ergebnisse: Über einen 4-Jahres-Zeitraum vom 1.2.2004–31.1.2008 wurden insgesamt 15 Patienten ermittelt, wovon 4 aus der berichtenden Klinik stammten (Durchschnittsalter: 57 Jahre; Frauen / Männer = 2 : 2). Die durchschnittliche Behandlungsdauer bis zum Auftreten der Komplikation betrug im Mittel 70 Tage (Spanne: 8–150 Tage). 13 Patienten wurden operiert, 2 Patienten verstarben ohne operative Versorgung jeweils an den Folgen der Peritonitis. Die Letalität betrug 33,3 % (n = 5 / 15), die Gesamtmorbidität 73,3 % (n = 11 / 15). In allen Fällen, in denen primär eine Anastomose angelegt wurde (n = 4), trat im Verlauf eine Anastomoseninsuffizienz auf (100 %). Die Rate der Wundheilungsstörungen betrug 38,5 % (n = 5 / 13). Schlussfolgerungen: Die Peritonitis nach GI-Perforation infolge einer Bevacizumab-Therapie stellt eine seltene Ak-assoziierte, aber ernst zu nehmende, da lebensbedrohliche Komplikation dar. Die im Zusammenhang mit der Neoangiogeneseinhibition gestörte Wundheilung bedingt Abweichungen im Management gastrointestinaler Perforationsereignisse im Vergleich zur etablierten chirurgischen Standardversorgung. Insbesondere ist zu empfehlen, auf Anastomosen oder Übernähungen zu verzichten und stattdessen, vergleichbar mit der Situation der Immunsuppression, großzügig die Indikation zur Stomaanlage zu stellen.

Abstract

Introduction: Bevacizumab (Avastin®, Fa. Roche, Genentech) is the first anti-angiogenic agent to be approved for the routine clinical treatment of cancer. Its toxicity profile is different to that of standard chemotherapeutic substances. Despite the rarity of gastrointestinal (GI) perforation in patients treated with bevacizumab, this serious adverse event results in significant morbidity and mortality. It was the aim of this study, based on exemplary cases of the reporting clinic as well as on published experiences, to characterise the specific clinical findings, the extraordinary pathogenesis, and the therapeutic outcome of such cases of peritonitis caused by perforation after antibody treatment. Methods: Data of all patients with perforation-caused peritonitis due to bevacizumab therapy since its clinical inauguration were sought in i) the database of the reporting clinic (case series), ii) in the published literature for comparison (historical comparative group) and iii) analysed with regard to results of the surgical management (evaluated parameters: rate of anastomotic insufficiency / disturbances of wound healing, morbidity, mortality). Results: Over a time period of 4 years (from 2 / 1 / 2004 to 1 / 31 / 2008), overall 15 patients were found in this study, among whom 4 patients came from the reporting clinic (mean age, 57 years; males : females = 2 : 2). The mean duration of antibody (Ab) treatment until occurrence of the complication was 70 days (range: 8–150 days). Thirteen patients underwent surgical intervention, 2 patients died due to severe peritonitis without any operation. The overall morbidity was 73.3 % (n = 11 / 15), the mortality was 33.3 % (n = 5 / 15). All patients with an anastomosis developed an anastomotic insufficiency (100 %). Wound healing complications occurred in 38.5 % of the subjects (n = 5 / 13). Conclusions: Peritonitis after GI perforation due to bevacizumab-based Ab treatment needs to be considered as a rare but serious and life-threatening complication. Impairment of wound healing because of the inhibition of angiogenesis is the reason for a different management of GI perforation under these conditions compared with the standard surgical treatment of peritonitis of other causes. In particular, it is recommended to avoid primary anastomosis and to prefer application of an intestinal stoma.

Bevacizumab - gastrointestinale (GI) Perforation - Peritonitis - chirurgisches Management

bevacizumab - gastrointestinal (GI) perforation - peritonitis - surgical management

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