Kolitis-assoziierte Karzinome, Prävention und Früherkennung

Zusammenfassung

Patienten mit chronisch entzündlichen Darmerkrankungen haben ein erhöhtes Risiko im Verlaufe ihrer Erkrankung ein kolorektales Karzinom (CRC) zu entwickeln. Das Risiko an einem Kolonkarzinom zu erkranken ist bei Patienten mit Colitis ulcerosa (CU) bis zu dreifach höher als in der Normalbevölkerung. Unter der Voraussetzung, dass das Kolon befallen ist, gelten ähnliche Risikofaktoren auch für den M. Crohn (MC) [1], die Datenlage ist jedoch deutlich spärlicher.
Das Risiko hängt im Wesentlichen von der Dauer und Ausdehnung der Erkrankung ab [2] [3] [4] [5], die Mortalität bei Patienten mit chronisch entzündlichen Darmerkrankungen ist dabei höher als bei Patienten mit sporadischem kolorektalen Karzinom [6]. Insbesondere jüngere Patienten mit Colitis ulcerosa oder Crohn-Kolitis über 10 Jahre andauernder Krankheitsgeschichte und ausgedehntem Befall haben ein hohes relatives Risiko (Alter 20-39 Jahre, RR 22) ein Karzinom zu entwickeln. Als Risikofaktoren sind weiterhin lange Krankheitsdauer, gleichzeitige geringe Krankheitsaktivität, frühe Erkrankung, gleichzeitig bestehende primär sklerosierende Cholangitis, Stenosen und der Nachweis einer „Backwash Ileitis” etabliert. Das Fehlen einer adäquaten Überwachung von Risikopatienten scheint ebenso wie eine unzureichende antientzündliche Therapie, ein Folsäuremangel und evtl. sogar ein Nichtraucherstatus das Risiko eines Kolitis-assoziierten Karzinoms (Ulcerative Colitis Associated Colorectal Cancer UCACRC) zu erhöhen [2] [3] [4] [7] [8] [9] [10] [11] [12]. Es gilt allgemein als akzeptiert, dass Dysplasien die Vorstufen des Kolitis-assoziierten Karzinoms bilden und als solche als Marker für ein Karzinomrisiko darstellen. Obwohl eindeutige Studien zum eigentlichen Nutzen fehlen wird daher eine Überwachung von Patienten mit länger andauernden chronisch entzündlichen Darmerkrankungen zur Früherkennung von Dysplasien und Karzinomen empfohlen [13] [14]. Während diese Strategien zur Prävention des kolorektalen Karzinoms heute durch Studien recht gut belegt sind, ist die Datenlage bezüglich einer Überwachungsstrategie zur Prävention des Colitis ulcerosa-assoziierten Karzinoms wesentlich schlechter. So bestehen große Unsicherheiten, welche Patientengruppe überwacht werden muss und wie eine solche Überwachung aussehen sollte [15]. Generell wird empfohlen, alle Patienten mit früher Manifestation, langjährigem und ausgedehntem Befall etwa 8-10 Jahre nach Erstmanifestation in ein Überwachungsprogramm einzuschließen. Dieses Programm sollte derzeit eine hohe Koloskopie in ein- bis zweijährlichen Intervallen mit der Entnahme von Stufenbiopsien zur frühzeitigen Entdeckung von Epitheldysplasien beinhalten. Besonderer Wert sollte dabei auf reichliche bioptische Probenentnahmen z. B. alle 10 cm des Darms und die konsequente Anwendung pathologischer Dysplasie-Kriterien z. B. nach dem IBD-DMSG-Standard gelegt werden [16] [17]. Bei Nachweis von highgrade-Dysplasien und DALM ist eine Proktokolektomie zu empfehlen, bei Nachweis von low-grade-Dysplasien ist zumindest die Überwachung zu intensivieren und auch hier ggfs. eine Proktokolektomie zu erwägen.

Abstract

Patients with chronic inflammatory bowel disease have a higher risk of developing colorectal carcinoma (CRC) during the course of their disease. The risk of colon carcinoma is up to three times higher in patients with ulcerative colitis than in the normal population. When the colon is affected, similar risk factors also hold for patients with Crohn's disease (CD) [1] although markedly few data are available.
The risk depends principally on the duration and extent of the disease [2] [3] [4] [5], with the mortality being higher for patients with chronic inflammatory bowel disease than for patients with sporadic colorectal carcinomas [6]. In particular, younger patients with ulcerative colitis or Crohn's colitis with a duration of disease of more than 10 years and extensive attack have a high relative risk of developing a carcinoma (age 20-39 years, RR 22). A long duration of disease with concomitant low disease activity, early onset, a simultaneously existing primary sclerorising cholangitis, stenoses, and the detection of backwash ileitis are still considered as risk factors. The lack of an adequate control of risk patients as well as an unsatisfactory anti-inflammation therapy, a folic acid deficiency and possibly, also non-smoking status, appear to increase the risk of colitis-associated carcinoma (ulcerative colitis associated colorectal cancer, UCACRC) [2] [3] [4] [7] [8] [9] [10] [11] [12]. It is generally accepted that dysplasias represent the precursors of colitis-associated carcinoma and as such constitute a marker for the carcinoma risk. Although unambiguous studies are lacking, the close monitoring for the early detection of dysplasias and carcinomas in patients with long-duration chronic inflammatory bowel diseases is recommended [13] [14]. Although these strategies for the prevention of colorectal carcinoma are now well-founded by studies, the available data on monitoring strategies for the prevention of ulcerative colitis-associated carcinomas are much less extensive. Thus, there are large differences of opinion as to which patient groups should be monitored and what such as monitoring scheme should look like [15]. It is generally recommended to include all patients with long-duration and extensive attack in a monitoring program at about 8-10 years after the first manifestation. This program should involve a high coloscopy with serial biopsies for the early detection of epithelial dysplasias at one to two year intervals. Particular attention should be paid to obtaining sufficient biopsy samples, e. g., at about every 10 cm along the bowel, and the consequent application of pathological dysplasia criteria, e. g., according to those set out in the IBD-DMSG standard [16] [17]. On detection of high-grade dysplasia and DALM, a proctocolectomy is recommended, on detection of low-grade dysplasias at least the monitoring should be intensified and a proctocolectomy considered.

Schlüsselwörter

Colitis ulcerosa - Kolorektale Karzinome - Prävention - Diagnose

Key words

Ulcerative colitis - colorectal carcinoma - prevention - diagnosis

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