Klinik und Pathobiologie von Dysplasien bei chronisch-entzündlichen Darmerkrankungen: aktuelle Empfehlungen zur Dysplasieüberwachung

Zusammenfassung

Patienten mit Colitis ulcerosa und M. Crohn tragen im Vergleich zur Normalbevölkerung ein ca. 10- bzw. 4fach erhöhtes Risiko, an einem kolorektalen Karzinom zu erkranken. Neben den typischen Karzinomlokalisationen im Colon sigmoideum und Rektum finden sich bei chronisch-entzündlichen Darmerkrankungen ebenso gehäuft Karzinome an anderen Lokalisationen, z. B. im rechten Hemikolon oder multifokal. Histologisch handelt es sich oft um schlecht differenzierte muzinöse Adenokarzinome Siegelringzellkarzinome. Die Häufigkeit kolorektaler Neoplasien hängt ab von Ausdehnung, Schwere, Dauer und Therapierbarkeit der chronischen Darmentzündung und scheint auf dieser Grundlage bei Colitis ulcerosa und M. Crohn vergleichbar zu sein.

Das Kolonkarzinom der chronisch-entzündlichen Darmerkrankung folgt in der Regel einer Kolitis-Dysplasie-Karzinom-Sequenz. Verlässliche molekularbiologische Marker zur Frühdiagnostik sind bislang nicht erhältlich; deshalb orientieren sich Überwachungsprogramme an der Entdeckung von Dysplasien (eindeutige intraepitheliale Neoplasie). Diese lassen sich mit einer Sensitivität von ca. 70-85 % mittels Koloskopie und Biopsie nachweisen.

Die Überwachung sollte bei Pankolitis nach 8 Erkrankungsjahren, bei Linksseitenkolitis nach 10-12 Jahren und bei Kolonbefall im Rahmen eines M. Crohn nach ca. 12 Jahren beginnen und jeweils in 1- bis 2-jährlichen Abständen erfolgen. 3-5 Stufenbiopsien sollten dabei alle 10 cm aus nichtentzündlichen Schleimhautarealen entnommen werden. Zudem ist besonders auf feine Strukturveränderungen der Mukosaoberfläche zu achten. Diese sollten genauso wie makroskopisch auffällige Bezirke (Plaques, knotige Strukturen, Stenosen) ausführlich biopsiert werden.

Die klinische Konsequenz eines positiven Dysplasienachweises ist bei einem Karzinomrisiko von 40-70 % die Proktokolektomie. Das höchste Karzinomrisiko besteht bei makroskopisch auffälligen Läsionen mit Dysplasien (sog. nichtadenomtypische Dysplasien), gefolgt von mehreren hochgradigen Dysplasien ohne makroskopische Läsion und mehreren niedriggradigen Dysplasien. Bei singulärem Nachweis von Dysplasien in flacher Mukosa wird eine endoskopische Kontrolle in 2-6 Monaten empfohlen, bei erneutem Nachweis die Kolektomie.

Pathobiology of dysplasia in chronic inflammatory bowel disease: Current recommendations for surveillance of dysplasia

Patients with ulcerative colitis and Crohn’s disease bear an about 10- and 4-fold increased risk, respectively, for developing colorectal carcinoma. Apart from typical locations of colorectal carcinoma in the sigmoid colon and rectum other locations were also often observed, e. g. right hemicolon or multifocal distribution. Histologically colorectal neoplasms frequently present as mucinous adenocarcinoma (signet-ring cell carcinoma). The risk for neoplasm depends on extension, severity, duration and therapeutic responsiveness of chronic colonic inflammation, and it seems pathogenetically to be similar in ulcerative colitis and Crohn’s disease.

Colorectal carcinoma in inflammatory bowel disease arises from epithelial dysplasia. Since there are no reliable biological markers available to date, surveillance-programs continue to rely on the discovery of dysplasia (unequivocal intraepithelial neoplasia). Detection of dysplasia by colonoscopy achieves 70-85 % sensitivity.

Endoscopic surveillance should start after 8 years of disease’s duration in pancolitis, after 10-12 years in left- sided colitis and after 12 years in Crohn’s disease of the colon, with regular intervals every 1-2 years. 3-5 biopsies should be done every 10 cm from mucosa free of inflammation. Additionally, every fine or discrete alteration of the mucosal surface should be recorded. Multiple biosies should also be taken from such minimal lesions as well as from more macroscopically suspicious areas like plaques, nodular lesions or stenosis.

The clinical consequence of a positive screening for dysplasia is colectomy because of an assumed risk of cancer of about 40-70 %. Dysplasia in macroscopically suspect areas bear the highest risk of cancer (non-adenoma like dysplasia), followed by multiple high-grade lesions without a macroscopic lesion, and multiple low-grade dysplasias. Detection of single dysplastic lesions in flat mucosa should be followed by a control endoscopy after 2-6 months, and if dysplasia is seen again, colectomy is recommended.

Schlüsselwörter

Colitis ulcerosa - M. Crohn - Dysplasie - Karzinom - Überwachung

Key words

Ulcerative colitis - Crohn's Disease - Dysplasia - Carcinoma Surveillance

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