Diagnostik und Therapie von Dünndarmpolypen mittels Push-and-Pull-Enteroskopie in Doppelballontechnik bei Patienten mit Peutz-Jeghers-Syndrom

Zusammenfassung

Einleitung: Das Peutz-Jeghers-Syndrom (PJS) ist charakterisiert durch eine Kombination aus mukokutanen Melaninpigmentierungen und hamartomatösen gastrointestinalen Polypen, die vorwiegend im Bereich des mittleren Dünndarms lokalisiert sind. Die Polypen können zur intestinalen Obstruktion sowie zu Invaginationen und Blutungen führen. Bis vor wenigen Jahren war die primär chirurgische Resektion sowie die intraoperative Polypektomie bei diesen Patienten die einzige Möglichkeit zur Therapie von Polypen im Bereich des mittleren Dünndarms. Die Push-and-Pull-Enteroskopie in Doppelballontechnik (DBE) eröffnet erstmals die Möglichkeit zur nichtchirurgischen Therapie. Methodik: Im Zeitraum von März 2003 bis September 2006 wurden insgesamt 16 Patienten mit PJS mittels DBE untersucht und endoskopisch therapiert. Dokumentiert wurden Größe, Anzahl und Lokalisation der diagnostizierten und endoskopisch resezierten Dünndarmpolypen sowie alle untersuchungs- und therapieassoziierten Komplikationen. Ergebnisse: Insgesamt wurden 47 DBE durchgeführt (oral 39, anal 8). Dabei fanden sich insgesamt 178 Polypen. 47 Polypen wurden aufgrund ihrer Größe und/oder ihres makroskopischen Erscheinungsbildes (Erosionen, Blutung, V. a. Malignität) endoskopisch polypektomiert. Die Größe der resezierten Dünndarmpolypen lag bei maximal 50 mm (Spanne 15 - 50 mm). Insgesamt traten 4 Komplikationen auf (2 Hb-relevante Blutungen, 1 Perforation, 1 Propofol-assoziierter Sättigungsabfall). Schlussfolgerung: Die DBE stellt ein sicheres Verfahren zur Diagnostik von Dünndarmpolypen bei Patienten mit PJS dar. Sie ermöglicht neben dem makroskopischen Eindruck eine Entnahme von Biopsien aus suspekten Arealen sowie eine genau Lokalisationsbestimmung und ggf. Markierung von primär operationswürdigen Befunden. Die DBE revolutioniert die therapeutischen Möglichkeiten für Polypen im Bereich des mittleren Dünndarms und minimiert die Indikation für ein primär chirurgisches Vorgehen.

Abstract

Introduction: Peutz-Jeghers syndrome (PJS) is characterised by a combination of hamartomatous gastrointestinal polyps and mucocutaneous melanin pigmentation. The polyps occur mainly in the small bowel and can lead to intestinal obstruction, intussusception and bleeding. Until only a few years ago, primary surgical resection and intraoperative endoscopy and polypectomy were the only available means of treating polyps in the mid-small bowel in these patients. With the introduction of double-balloon enteroscopy (DBE), we now have not only an improved diagnostic tool but also a non-surgical treatment option. Methods: Between March 2003 and September 2006 a total of 16 patients with PJS were examined by DBE and treated endoscopically. The size, number and location of the diagnosed and endoscopically resected small-bowel polyps were documented as were all complications associated with the examination or treatment. Results: A total of 47 DBE-procedures were performed (oral approach 39, anal approach 8). The examinations revealed a total of 178 polyps. 47 polyps were removed by endoscopic polypectomy on the grounds of their size and/or gross appearance. The largest small-bowel polyp resected was 50 mm (min. 15 mm, max. 50 mm). A total of four complications occurred (2 episodes of bleeding with a fall in Hb, 1 perforation, 1 propofol-associated decrease in oxygen saturation). Conclusion: DBE is a safe and reliable procedure for the diagnosis of small-bowel polyps in patients with PJS. In addition to macroscopic assessment and biopsy of suspicious areas, it permits the exact localisation as well as preoperative marking of polyps that are primary candidates for surgery. DBE revolutionises the therapeutic options for polyps in the region of the mid-small bowel and limits the indications for primary surgical management.

Peutz-Jeghers-Syndrom - Dünndarmpolypen - Push-and-Pull-Enteroskopie in Doppelballontechnik - endoskopische Polypektomie

Peutz-Jeghers syndrome - small bowel polyps - push-and-pull enteroscopy in double-balloon technique - endoscopic polypectomy

Literatur

• 1 Hemminki A, Tomlinson I, Markie D. et al . Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis.  Nat Genet. 1997;  15 87-90
• 2 Amos C I, Bali D, Thiel T J. et al . Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p.  Cancer Res. 1997;  57 3653-3656
• 3 Jenne D E, Reimann H, Nezu J. et al . Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.  Nat Genet. 1998;  18 38-43
• 4 Hemminki A, Markie D, Tomlinson I. et al . A serine/threonine kinase gene defective in Peutz-Jeghers syndrome.  Nature. 1998;  391 (6663) 184-187
• 5 Boardman L A, Couch F J, Burgart L J. et al . Genetic heterogeneity in Peutz-Jeghers syndrome.  Hum Mutat. 2000;  16 23-30
• 6 Wei C, Amos C I, Rashid A. et al . Correlation of staining for LKB1 and COX-2 in hamartomatous polyps and carcinomas from patients with Peutz-Jeghers syndrome.  J Histochem Cytochem. 2003;  51 1665-1672
• 7 Ballhausen W G, Gunther K. Genetic screening for Peutz-Jeghers syndrome.  Expert Rev Mol Diagn. 2003;  3 471-479
• 8 Amos C I, Keitheri-Cheteri M B, Sabripour M. et al . Genotype-phenotype correlations in Peutz-Jeghers syndrome.  J Med Genet. 2004;  41 327-333
• 9 Schumacher V, Vogel T, Leube B. et al . Gene symbol: STK11. Disease: Peutz-Jeghers syndrome.  Hum Genet. 2005;  116 540
• 10 Mehenni H, Resta N, Park J G. et al . Cancer risks in LKB1 germline mutation carriers.  Gut. 2006;  55 984-990
• 11 Weber F P. Patches of deep pigmentation of oral mucous membrane not connected with Addison`s disease.  Q J Med. 1949;  12 404-408
• 12 Peutz H, Mc Kusick V A, Katz K H. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits: A syndrom of diagnostic significance.  N Engl J Med. 1949;  241 993-1005
• 13 Jeghers H. Pigmentation of skin.  N Engl J med. 1944;  231 88-100, 122 - 136, 181 - 189
• 14 Dozois R R, Judd E S, Dahlin D C. et al . The Peutz-Jeghers syndrome. Is there a predisposition to the development of intestinal malignancy?.  Arch Surg. 1969;  98 509-517
• 15 Linos D A, Dozois R R, Dahlin D C. et al . Does Peutz-Jeghers syndrome predispose to gastrointestinal malignancy? A later look.  Arch Surg. 1981;  116 1182-1184
• 16 Dodds W J, Schulte W J, Hensley G T. et al . Peutz-Jeghers syndrome and gastrointestinal malignancy.  Am J Roentgenol Radium Ther Nucl Med. 1972;  115 374-377
• 17 Papaioannou A, Critselis A. Malignant changes in Peutz-Jeghers syndrome.  N Engl J Med. 1973;  289 694
• 18 Giardiello F M, Welsh S B, Hamilton S R. et al . Increased risk of cancer in the Peutz-Jeghers syndrome.  N Engl J Med. 1987;  316 1511-1514
• 19 Spigelman A D, Murday V, Phillips R K. Cancer and the Peutz-Jeghers syndrome.  Gut. 1989;  30 1588-1590
• 20 Giardiello F M, Brensinger J D, Tersmette A C. et al . Very high risk of cancer in familial Peutz-Jeghers syndrome.  Gastroenterology. 2000;  119 1447-1453
• 21 Conneely J B, Kell M R, Boran S. et al . A case of bilateral breast cancer with Peutz-Jeghers syndrome.  Eur J Surg Oncol. 2006;  32 121-122
• 22 Brinster D R, Raper S E. Synchronous colon and pancreatic cancers in a patient with Peutz-Jeghers syndrome: report of a case and review of the literature.  Surgery. 2004;  135 352-354
• 23 Nguyen H N. Tumor risk in Peutz-Jegher’s syndrome.  Dtsch Med Wochenschr. 2002;  127 1272-1273
• 24 Mehenni H, Resta N, Park J G. et al . Cancer risks in LKB1 germline mutation carriers.  Gut. 2006;  55 984-990
• 25 Hearle N, Schumacher V, Menko F H. et al . Frequency and spectrum of cancers in the peutz-jeghers syndrome (abstract).  Clin Cancer Res. 2006;  12 3209-3215
• 26 Foley T R, McGarrity T J, Abt A B. Peutz-Jeghers syndrome: a clinicopathologic survey of the „Harrisburg family” with a 49-year follow-up.  Gastroenterology. 1988;  95 1535-1540
• 27 Burdick D, Prior J T. Peutz-Jeghers syndrome. A clinicopathologic study of a large family with a 27-year follow-up.  Cancer. 1982;  50 2139-2146
• 28 Bartholomew L G, Dahlin D C, Waugh J M. Intestinal polyposis associated with mucocutaneous melanin pigmentation (Peutz-Jeghers syndrome). Review of the literature and report of six cases with special reference to pathologic findings.  Gastroenterology. 1957;  32 434-451
• 29 Bartholomew L G, Moore C E, Dahlin D C. et al . Intestinal polyposis with mucocutaneous pigmentation.  Surg Gynecol Obstet. 1962;  115 1-11
• 30 Utsunomiya J, Gocho H, Miyanaga T. et al . Peutz-Jeghers syndrome: its natural course and management.  Johns Hopkins Med J. 1975;  136 71-82
• 31 Westerman A M, Entius M M, Baar de E. et al . Peutz-Jeghers syndrome: 78-year follow-up of the original family.  Lancet. 1999;  353 (9160) 1211-1215
• 32 Spigelman A D, Arese P, Phillips R K. Polyposis: the Peutz-Jeghers syndrome.  Br J Surg. 1995;  82 1311-1314
• 33 Burke W, Daly M, Garber J. et al . Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium.  JAMA. 1997;  277 997-1003
• 34 The John Hopkins guide for patients and families: Peutz-Jeghers syndrome. Baltimore; John Hopkins University 2001
• 35 Williams C B, Goldblatt M, Delaney P V. ‘Top and tail endoscopy’ and follow-up in Peutz-Jeghers syndrome.  Endoscopy. 1982;  14 82-84
• 36 Paterlini A, Huscher C, Salmi A. Jejunal endoscopic polypectomy in the Peutz-Jeghers syndrome.  Endoscopy. 1983;  15 270-271
• 37 Coevorden van F, Mathus-Vliegen E M, Brummelkamp W H. Combined endoscopic and surgical treatment in Peutz-Jeghers syndrome.  Surg Gynecol Obstet. 1986;  162 426-428
• 38 Spigelman A D, Thomson J P, Phillips R K. Towards decreasing the relaparotomy rate in the Peutz-Jeghers syndrome: the role of peroperative small bowel endoscopy.  Br J Surg. 1990;  77 301-302
• 39 Panos R G, Opelka F G, Nogueras J J. Peutz-Jeghers syndrome. A call for intraoperative enteroscopy.  Am Surg. 1990;  56 331-333
• 40 Sudduth R H, Bute B G, Schoelkopf L. et al . Small bowel obstruction in a patient with Peutz-Jeghers syndrome: the role of intraoperative endoscopy.  Gastrointest Endosc. 1992;  38 69-72
• 41 Spigelman A D, Arese P, Phillips R K. Polyposis: the Peutz-Jeghers syndrome.  Br J Surg. 1995;  82 1311-1314
• 42 McGrath D R, Spigelman A D. Preventive measures in Peutz-Jeghers syndrome.  Fam Cancer. 2001;  1 121-125
• 43 Seenath M M, Scott M J, Morris A I. et al . Combined surgical and endoscopic clearance of small-bowel polyps in Peutz-Jeghers syndrome.  J R Soc Med. 2003;  96 505-506
• 44 Giardiello F M, Trimbath J D. Peutz-Jeghers syndrome and management recommendations.  Clin Gastroenterol Hepatol. 2006;  4 408-415
• 45 Ohmiya N, Taguchi A, Shirai K. et al . Endoscopic resection of Peutz-Jeghers polyps throughout the small intestine at double-balloon enteroscopy without laparotomy.  Gastrointest Endosc. 2005;  61 140-147
• 46 De Palma G D, Rega M, Ciamarra P. et al . Small-bowel polyps in Peutz-Jeghers syndrome: diagnosis by wireless capsule endoscopy.  Endoscopy. 2004;  36 1039
• 47 Parsi M A, Burke C A. Utility of capsule endoscopy in Peutz-Jeghers syndrome.  Gastrointest Endosc Clin N Am. 2004;  14 159-167
• 48 Mata A, Llach J, Castells A. et al . A prospective trial comparing wireless capsule endoscopy and barium contrast series for small-bowel surveillance in hereditary GI polyposis syndromes.  Gastrointest Endosc. 2005;  61 721-725
• 49 Schulmann K, Hollerbach S, Kraus K. et al . Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes.  Am J Gastroenterol. 2005;  100 27-37
• 50 Soares J, Lopes L, Vilas Boas G. et al . Wireless capsule endoscopy for evaluation of phenotypic expression of small-bowel polyps in patients with Peutz-Jeghers syndrome and in symptomatic first-degree relatives.  Endoscopy. 2004;  36 1060-1066
• 51 Caspari R, Falkenhausen von M, Krautmacher C. et al . Comparison of capsule endoscopy and magnetic resonance imaging for the detection of polyps of the small intestine in patients with familial adenomatous polyposis or with Peutz-Jeghers’ syndrome.  Endoscopy. 2004;  36 1054-1059
• 52 Schulmann K, Schmiegel W. Capsule endoscopy for small bowel surveillance in hereditary intestinal polyposis and non-polyposis syndromes.  Gastrointest Endosc Clin N Am. 2004;  14 149-158
• 53 Yamamoto H, Sekine Y, Sato Y. et al . Total enteroscopy with a nonsurgical steerable double-balloon method.  Gastrointest Endosc. 2001;  53 216-220
• 54 May A, Nachbar L, Wardak A. et al . Double-balloon enteroscopy: preliminary experience in patients with obscure gastrointestinal bleeding or chronic abdominal pain.  Endoscopy. 2003;  35 985-991
• 55 Yamamoto H, Kita H, Sunada K. et al . Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases.  Clin Gastroenterol Hepatol. 2004;  2 1010-1016
• 56 Ell C, May A, Nachbar L. et al . Push-and-pull enteroscopy in the small bowel using the double-balloon technique: results of a prospective European multicenter study.  Endoscopy. 2005;  37 613-616
• 57 May A, Nachbar L, Ell C. Double-balloon enteroscopy (push-and-pull enteroscopy) of the small bowel: feasibility and diagnostic and therapeutic yield in patients with suspected small bowel disease.  Gastrointest Endosc. 2005;  62 62-70
• 58 Di Caro S, May A, Heine D G. et al . The European experience with double-balloon enteroscopy: indications, methodology, safety, and clinical impact.  Gastrointest Endosc. 2005;  62 545-550
• 59 Oncel M, Remzi F H, Church J M. et al . Benefits of ‘clean sweep’ in Peutz-Jeghers patients.  Colorectal Dis. 2004;  6 332-335
• 60 Lin B C, Lien J M, Chen R J. et al . Combined endoscopic and surgical treatment for the polyposis of Peutz-Jeghers syndrome.  Surg Endosc. 2000;  14 1185-1187
• 61 Pennazio M, Rossini F P. Small bowel polyps in Peutz-Jeghers syndrome: management by combined push enteroscopy and intraoperative enteroscopy.  Gastrointest Endosc. 2000;  51 304-308
• 62 Edwards D P, Khosraviani K, Stafferton R. et al . Long-term results of polyp clearance by intraoperative enteroscopy in the Peutz-Jeghers syndrome.  Dis Colon Rectum. 2003;  46 48-50
• 63 Heldwein W, Dollhopf M, Rosch T. et al . The Munich Polypectomy Study (MUPS): Prospective Analysis of Complications and Risk Factors in 4000 Colonic Snare Polypectomies (abstract).  Endoscopy. 2005;  37 1116-1122