Download PDF
Z Gastroenterol 2001; 39(10): 861-875
DOI: 10.1055/s-2001-17870
Übersichten
© Karl Demeter Verlag im Georg Thieme Verlag Stuttgart · New York

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

Pathobiology of dysplasia in chronic inflammatory bowel disease: Current recommendations for surveillance of dysplasiaM. Raithel1 , M. Weidenhiller1 , D. Schwab1 , S. Müller2 , E. G. Hahn1
  • Medizinische Klinik I mit Poliklinik, Universität Erlangen-Nürnberg, Erlangen
  • , Institut für Pathologie der Universität Erlangen-Nürnberg, Erlangen
Further Information

Publication History

31.8.2000

8.2.2001

Publication Date:
17 October 2001 (online)

Also available at
    Permissions and Reprints

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

Literatur

  • 1 Axon A TR. Cancer surveillance in ulcerative colitis - a time for reappraisal.  Gut. 1994;  35 587-589
    Google Scholar
  • 2 Ransohoff D F. Colon cancer in ulcerative colitis.  Gastroenterology. 1988;  94 1089-1091
    Google Scholar
  • 3 Bargen J A. Chronic ulcerative colitis associated with malignant disease.  Arch Surg. 1928;  17 561-576
    Google Scholar
  • 4 Weedon D D, Shorter R G, Ilstrup D M. Crohn’s disease and cancer.  N Engl J Med. 1973;  289 1099-1103
    Google Scholar
  • 5 Stange E F, Riemann J, von Herbay A. et al . Diagnostik und Therapie der Colitis ulcerosa - Ergebnisse einer evidenzbasierten Konsensuskonferenz der Deutschen Gesellschaft für Verdauungs- und Stoffwechselerkrankungen.  Z Gastroenterol. 2001;  39 19-72
    Google Scholar
  • 6 Gyde S N. Cancer in inflammatory bowel disease.  Scand J Gastroenterol. 1989;  24 (Suppl. 170) 79-80
    Google Scholar
  • 7 Broomé U, Lindberg G, Löfberg R. Primary sclerosing cholangitis in ulcerative Colitis - a risk factor for the development of dysplasia and DNA aneuploidy?.  Gastroenterology. 1992;  102 1877-1880
    Google Scholar
  • 8 Brentnall T A, Crispin D A, Bronner M P. et al . Microsatellite instability in nonneoplastic mucosa from patients with chronic ulcerative colitis.  Cancer Res. 1996;  56 1237-1240
    Google Scholar
  • 9 Bernstein C N. ALMs versus DALMs in ulcerative colitis: Polypectomy or colectomy.  Gastroenterology. 1999;  117 1488-1491
    Google Scholar
  • 10 Ottenjann R, Classen M. Gastroenterologische Endoskopie. Stuttgart; Enke 1991
    Google Scholar
  • 11 Choi P, Kim W H. Colon cancer surveillance.  Gastroenterol Clin North Am. 1995;  24 671-687
    Google Scholar
  • 12 Felder J B, Korelitz B I. Cancer in inflammatory bowel disease.  Curr Opin Gastroenterol. 1993;  9 552-559
    Google Scholar
  • 13 Provenzale D, Kowdley K V, Arora S, Wong J B. Prophylactic colectomy or surveillance of chronic ulcerative colitis? A decision analysis.  Gastroenterology. 1995;  109 1188-1196
    Google Scholar
  • 14 Nuako K W, Ahlquist D A, Sandborn W J. et al . Primary sclerosing cholangitis and colorectal carcinoma in patients with chronic ulcerative colitis.  Cancer. 1998;  82 822-826
    Google Scholar
  • 15 Pohl C, Hombach A, Kruis W. Mindert antientzündliche Therapie das Karzinomrisiko bei CED?.  MMW - Fortschr Med. 1999;  141 445-449
    Google Scholar
  • 16 Korelitz B I. Carcinoma of the intestinal tract in Crohn’s disease: Results of a survey conducted by the National Foundation for Ileitis and Colitis.  Am J Gastroenterol. 1983;  78 44-46
    Google Scholar
  • 17 Ekbom A. et al . Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement.  Lancet. 1990b;  336 357-358
    Google Scholar
  • 18 Korelitz B I, Felder J B. Gastrointestinal complications of ulcerative colitis and Crohn’s disease. Kirsner JB, Shorter RG Inflammatory bowel disease Baltimore; Williams & Wilkins 1995 4th ed
    Google Scholar
  • 19 Lauwers G. Mucosal dysplasia in inflammatory bowel disease. Korelitz BI, Sohn N Management of inflammatory bowel disease St. Louis; Mosby-Year 1992
    Google Scholar
  • 20 Stenton W F. Inflammatory bowel disease. Yamada T et al Textbook of gastroenterology Philadelphia; Lippincott 1995 2nd ed
    Google Scholar
  • 21 Mueller E, Vieth M, Stolte M, Mueller J. The differentiation of true adenomas from colitis-associated dysplasia in ulcerative colitis: A comparative immunhistochemical study.  Hum Pathol. 1999;  30 898-905
    Google Scholar
  • 22 Lennard-Jones J E, Melville D M, Morson B C. et al . Precancer and cancer inextensive ulcerative colitis: Findings among 401 patients over 22 years.  Gut. 1990;  31 800-806
    Google Scholar
  • 23 Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J. Colorectal cancer prevention in ulcerative colitis: A case control study.  Alimont Phermacol Ther. 2000;  14 145-153
    Google Scholar
  • 24 Connell W R, Lennard-Jones J E, Williams C B. et al . Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.  Gastroenterology. 1994;  107 934-944
    Google Scholar
  • 25 Vieth M, Stolte M, Mueller E, Mueller J, Schneider A. Bioptische Differentialdiagnostik von Adenomen, Dysplasien und Karzinomen bei Patienten mit Colitis ulcerosa.  Leber, Magen, Darm. 2000;  30 125-132
    Google Scholar
  • 26 Nugent F W, Haggitt R C, Gilpin P A. Cancer surveillance in ulceratice colitis.  Gastroenterology. 1991;  100 1241-1248
    Google Scholar
  • 27 Rubin P H, Friedman S, Harpaz N. et al . Colonoscopic polypectomy in chronic colitis:Conservative management after endoscopic resection of dysplastic polyps.  Gastroenterology. 1999;  117 1295-1300
    Google Scholar
  • 28 Engelsgjerd M, Farraye F A, Odze R D. Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis.  Gastroenterology. 1999;  117 1288-1294
    Google Scholar
  • 29 Marchesa P, Lashner B A, Lavery I C. et al . The risk of cancer and dysplasia among ulcerative colitis patients with primary sclerosing cholangits.  Am J Gastroenterol. 1997;  92 1285-1288
    Google Scholar
  • 30 Leidenius M HK, Färkkilä M A, Kärkkäinen P. et al . Colorectal dysplasia and carcinoma in patients with ulcerative colitis and primary sclerosing cholangitis.  Scand J Gastroenterology. 1997;  32 706-711
    Google Scholar
  • 31 Petras R E, Mir-Madilessi S H, Farmer R G. Crohn’s disease and intestinal carcinoma.  Gastroenterology. 1987;  93 1307-1314
    Google Scholar
  • 32 Korelitz B I, Lauwers G Y, Sommers S C. Rectal mucosal dysplasia in Crohn’s disease.  Gut. 1990;  31 1382-1386
    Google Scholar
  • 33 Riddell R H, Goldman H, Ransohoff D F. et al . Dysplasia in inflammatory bowel disease: Standardized classification with provisional clinical implications.  Hum Pathol. 1983;  14 931-968
    Google Scholar
  • 34 Itzkowitz S H, Young E, Bubois D. et al . Sialysyl-Tn antigen is prevalent and precedes dysplasia in ulcerative colitis: A retrospective case-control study.  Gastroenterology. 1996;  110 694-704
    Google Scholar
  • 35 Schneider A, Stolte M. Differential diagnosis of adenomas and dysplastic lesions in patients with ulcerative colitis.  Z Gastroenterol. 1993;  31 653-656
    Google Scholar
  • 36 Collier P E, Turowski  P, Diamond D L. Small intestine adenocarcinoma complicating regional enteritis.  Cancer. 1985;  55 516-521
    Google Scholar
  • 37 Glotzer D J. The risk of cancer in Crohn’s disease.  Gastroenterology. 1985;  89 438-440
    Google Scholar
  • 38 Nikia G, Eisner T, Katz S, Levin R, Eskries D. et al . Crohn’s disease and colorectal carcinoma: Rectal cancer complicating long- standing active perianal disease.  Am J Gastroenterol. 1995;  90 216-219
    Google Scholar
  • 39 Fresko D, Lazarus S S, Dotan J. et al . Early presentation of carcinoma of the small bowel in Crohn’s disease.  Gastroenterology. 1982;  82 783-789
    Google Scholar
  • 40 Yamazaki Y, Ribeiro M B, Sachar D B. Malignant colorectal strictures in Crohn’s disease.  Am J Gastroenterol. 1991;  86 882-885
    Google Scholar
  • 41 Borchard F, Heilmann K L, Hermanek P. et al . Definition und klinische Bedeutung der Dysplasie im Verdauungstrakt.  Pathologe. 1991;  12 50-56
    Google Scholar
  • 42 Rubin C E, Haggitt R C, Burmer G C. DNA aneuploidy in Crohn’s disease and ulcerative colitis: Results of a comparative flow cytometric study.  Gut. 1992;  33 663-667
    Google Scholar
  • 43 Ilyas M, Talbot I C. p53 expression in ulcerative colitis: A longitudinal study.  Gut. 1995;  37 802-804
    Google Scholar
  • 44 Kreißler-Haag D, Ecker K W, Schüder  M. et al . Karzinome bei chronisch entzündlichen Darmerkrankungen.  Coloproctology. 1996;  18 117-123
    Google Scholar
  • 45 Porschen J, Strohmeyer G. Kolorektales Karzinomrisiko bei Colitis ulcerosa - Überwachungsstrategien und Identifikation von Risikopatienten.  Z Gastroenterol. 1992;  30 585-593
    Google Scholar
  • 46 Blackstone M O, Riddell R H, Rogers B HG. et al . Dysplasia-associated lesion of mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: An indication for colectomy.  Gastroenterology. 1981;  80 366-374
    Google Scholar
  • 47 Keller R, Brandt B, Terpe H J. et al . Density gradient centrifugation of colonic fluid after segmental lavage: A method of purification of exfoliative epithelial colonic cells for cytological interpretation and image cytometry in patients with long-standing ulcerative colitis.  Am J Gastroenterol. 1999;  94 404-409
    Google Scholar
  • 48 Mennigen R, Kusche J, Streffer C. et al . Diamine oxidase activities in the large bowel mucosa of ulcerative colitis patients.  Agents Actions. 1990;  30 264-266
    Google Scholar
  • 49 Fischbach W, Mössner J, Seyschab H. Tissue carcinoembryonic antigen and DNA aneuploidy in precancerous and cancerous colorectal lesions.  Cancer. 1990;  65 1820-1824
    Google Scholar
  • 50 Souza F R, Yin J, Smolinski K N. et al . Frequent mutations of the E2F-4 cell cycle gene in primary human gastrointestinal tumors.  Cancer Res. 1997;  57 2350-2353
    Google Scholar
  • 51 Ahnen D J, Warren G H, Greene L J, Singleton J W, Brown W R. Search for a specific marker of mucosal dysplasia in chronic ulcerative colitis.  Gastroenterology. 1987;  93 1346-1355
    Google Scholar
  • 52 Dimitriadou V, Koutsilieris M. Mast cell-tumor cell interactions: For or against tumour growth and metastasis?.  Anticancer Res. 1997;  17 1541-1550
    Google Scholar
  • 53 Norby K. Evidence of mast-cell histamine being mitogenic in intact tissue.  Agents Actions. 1985;  16 287-290
    Google Scholar
  • 54 Okayasu I, Ohkusa T, Kajiura K. et al . Promotion of colorectal neoplasia in experimental murine ulcerative colitis.  Gut. 1996;  39 87-92
    Google Scholar
  • 55 Kusche J, Mennigen R, Leisten L. et al . Large bowel tumor promotion by inhibition of mucosal diamine oxidase in rats II. Biochemical aspects.  Biogenic Amines. 1989a;  6 27-38
    Google Scholar
  • 56 Bieganski T, Braun R, Kusche J. N-methyl-N-formylhydrazine: A toxic and mutagenic inhibitor of intestinal diamine oxidase.  Agents Actions. 1984;  14 351-355
    Google Scholar
  • 57 Schmidt W U, Sattler J, Hestberg R. et al . Human intestinal diamine oxidase (DAO) acticity in Crohn’s disease: A new marker for disease assessment?.  Agents Actions. 1990;  30 267-270
    Google Scholar
  • 58 Hesterberg R, Kusche J, Stahlknecht C D. et al . The start of a programme for measuring diamine oxidase activity in biopsy specimens of human rectal mucosa.  Agents Actions. 1981;  11 33-37
    Google Scholar
  • 59 Raithel M, Ulrich P, Hochberger J, Hahn E G. Measurement of gut diamine oxidase activity: Diamine oxidase as a new biologic marker of colorectal proliferation?.  Ann N Y Acad Sci. 1998;  859 262-266
    Google Scholar
  • 60 Hill M J, Lennard-Jones J E, Mellville D M, Neale K, Ritchie J K. Fecal bile acids, dysplasia, and carcinoma in ulcerative colitis.  Lancet. 1987;  2 185-186
    Google Scholar
  • 61 Hill M J, Lennard-Jones J E, Mellville D M. et al . Association of fecal bile acids and colon cancer in ulceratice colitis.  Gastroenterology. 1988;  94 242-243
    Google Scholar
  • 62 Kurtz R C. Association of fecal bile acids and colon cancer in ulcerative colitis.  Gastroenterology. 1988;  94 242-243
    Google Scholar
  • 63 Biasco G, Zannoni U, Paganelli G M. et al . Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis.  Cancer Epidemiol Biomarkers Prev. 1997;  6 469-471
    Google Scholar
  • 64 Lashner B A, Provencher K S, Seidner D L. et al . The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis.  Gastroenterology. 1997;  112 29-32
    Google Scholar
  • 65 Rashid A, Pizer E S, Moga M. et al . Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia.  Am J Pathol. 1997;  150 201-208
    Google Scholar
  • 66 Kornbluth A, Present D, Rubin P. Sialosyl-Tn antigen (s-Tn) in non-dysplastic biopsies may predict development of cancer or dysplasia in ulcerative colitis (abstract).  Gastroenterology. 1991;  100 A 221
    Google Scholar
  • 67 Löfberg R, Broström O, Karlen P. et al . Aneuploidy in ulcerative colitis; reproducibility, topographic distribution, and relation to dysplasia.  Gastroenterology. 1992;  102 1149-1154
    Google Scholar
  • 68 Gloria L, Cravo M, Pinto A. et al . DNA hypomethylation and proliferative activity are increased in the rectal mucosa of patients with long-standing ulcerative colitis.  Cancer. 1996;  78 2300-2306
    Google Scholar
  • 69 Frykholm G, Enbled P, Pahlman L. Expression of the carcinoma associated antigen CA 19-9 and CA50 in inflammatory bowel disease.  Dis Colon Rectum. 1987;  30 545-548
    Google Scholar
  • 70 Allen D C, Foster H, Orchin J C. Immunohistochemical staining of colorectal tissues with monoclonal antibodies to ras oncogene p21 product and carbohydrate determinant antigen 19-9.  J Clin Pathol. 1987;  40 157-162
    Google Scholar
  • 71 Keller R, Fischbach W. Endoscopic fluorescence detection of dysplasia in patients with Barrett’s esophagus, ulcerative colitis or colorectal adenomas.  Z Gastroenterol. 1999;  37 761-763
    Google Scholar
  • 72 Messmann H. 5-Aminolevulinic acid-induced protoporphyrin IX for the detection of gastrointestinal dysplasia.  Gastrointest Endosc Clin N Am. 2000;  10 497-512
    Google Scholar
  • 73 Messmann H. Fluorescence endoscopy in gastroenterology.  Z Gastroenterol. 2000;  38 21-30
    Google Scholar
  • 74 Choi P M, Nugent F W, Schoetz D J. et al . Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis.  Gastroenterology. 1993;  105 418-424
    Google Scholar
  • 75 Ransohoff D F, Riddel R H, Levin B. Ulcerative colitis and colonic cancer: Problems in assessing the diagnostic usefulness of mucosal dysplasia.  Dis Colon Rectum. 1985;  28 383-386
    Google Scholar
  • 76 Biasco G, Brand G, Paganelli G M. Colorectal cancer in patients with ulcerative colitis.  Cancer. 1995;  75 2045-2050
    Google Scholar
  • 77 Nagasako K, Iizuka B, Miyazaki J, Fuijmori T. Colonoscopic diagnosis of dysplasia and early cancer in long-standing colitis.  Gastroenterology. 1995;  30 36-39
    Google Scholar
  • 78 Woolrich A J, DaSilva M M, Korelitz B I. Surveillance in the routine management of ulcerative colitis: The predictive value of low-grade dysplasia for cancer.  Gastroenterology. 1992;  103 431-438
    Google Scholar
  • 79 Neuhaus H. Vorsorge zur Prävention oder Früherkennung des kolorektalen Karzinoms.  Dtsch Ärztebl. 1998;  95 A530-537
    Google Scholar
  • 80 Wright C L, Riddell R H. The pathology and politics of dysplasia in ulcerative colitis.  Curr Opin Gastroenterol. 1989;  14 11-14
    Google Scholar
  • 81 Stange E F, Schreiber S, Raedler  A. et al . Therapie des Morbus Crohn - Ergebnisse einer Konsensuskonferenz der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten.  Z Gastroenterol. 1997;  35 541-554
    Google Scholar
  • 82 Selby W. The natural history of ulcerative colitis. Gibson PR Ulcerative colitis. Baillieres Clin Gastroenterol 1997 11: 53-64
    Google Scholar
  • 83 Macrae F A, Bhathal P S. Colonoscopy and biopsy. Gibson PR Ulcerative colitis. Baillieres Clin Gastroenterol 1997 11: 65-82
    Google Scholar
  • 84 Shetty K, Rybicki L, Brezinski A, Carey W D, Lashner B A. The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis.  Am J Gastroenterol. 1999;  94 1643-1649
    Google Scholar
  • 85 Shepherd N A. Pouchitis and neoplasia in the pelvic ileal reservoir.  Gastroenterology. 1995;  109 1381-1296
    Google Scholar
  • 86 Lindberg B, Persson B, Veress. et al . Twenty years colonoscopic surveillance of patients with ulcerative colitis.  Scand J Gastroenterol. 1996;  31 1195-1204
    Google Scholar
  • 87 Endlicher E, Knuechel R, Schoelmerich J, Messmann H. Photodynamic diagnosis (PDD) of dysplasia in ulcerative colitis after sensitization with 5-aminolevulinic acid (ALA).  Gastroenterology. 1999;  114 A253
    Google Scholar
  • 88 Bernstein C N, Shanahan F, Weinstein W M. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis?.  Lancet. 1994;  343 71-74
    Google Scholar

Anschrift für die Verfasser

PD Dr. med. Martin Raithel

Medizinische Klinik I mit Poliklinik der Universität Erlangen-Nürnberg
Funktionelle Gewebediagnostik, Gastroenterologie

Krankenhausstraße 12

91054 Erlangen

Email: martin.raithel@med1.imed.uni-erlangen.de