Endoscopic Evaluation of Duodenal Polyposis in Patients With Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder that predisposes to a number or malignant disorders \[1,2\]. Clinically, FAP presents with an abnormal number of colorectal polyps (100-5000), while it genetically is defined by mutations in the APC-gene \[1\]. Historically, colorectal cancer has been the major cause of deaths for FAP patient. However, as the incidence of colorectal cancer has decreased with the use of prophylactic colectomy, the incidence of duodenal cancer has increased \[3,4\]. It is estimated that the cumulative lifetime risk of duodenal polyposis exceeds 95% \[1,5\]. The predictor of duodenal cancer is duodenal polyposis, which is almost inevitable in patients with FAP. In 1989 the Spigelman score was introduced in order to assess the severity of duodenal polyposis and stratify patients according to risk of duodenal cancer (Table 1) \[6\]. It is a composite score that includes two endoscopic parameters (number and maximum size of polyps, respectively) and two histopathological parameters (histological subtype and grade of dysplasia). The score ranges from 0-12 and it has been classified in four stages. The 10-year risk of developing duodenal cancer corresponds with the Spigelman stage ranging from ≈0 for stage 0-1 to 36% for stage 4 \[7\]. Besides duodenal cancer, the indications of cancer prophylactic surgical resection are debatable, but generally recommended in the case of Spigelman stage 4 or high-grade dysplasia. Table 1 Spigelman Classification for duodenal polyposis Criterion 1 point 2 points 3 points Polyp number 1-4 5-20 \>20 Polyp size (mm) 1-4 5-10 \>20 Histology Tubular Tubulovillous Villous Dysplasia Low grade\* High grade\* Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points. \*Originally, 3 grades of dysplasia were incorporated. While the correlation to cancer has been explored in several studies, the validation and the reproducibility of the Spigelman score remains somewhat unclear. The primary aim of this study is to assess the inter- and intra-observer agreement of the Spigelman score for experienced endoscopists using state-of-the-art high-definition (HD) endoscopes. Hypothesis: The Spigelman score has perfect reproducibility for endoscopic experts (κ\>0.80 with 95% CI.).

Sex

All

Inclusion Criteria:

* Patients known with FAP (having either an APC mutation, or \>100 colorectal adenomas and a positive family history) and with an indication of EGD as part of their surveillance or therapeutic program.

Exclusion Criteria:

* Patients, in whom the standard biopsy protocol cannot be fulfilled due to vital anticoagulant therapy, liver failure etc.

• BACKGROUNDVasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Engel C, Frayling I, Friedl W, Hes FJ, Hodgson S, Jarvinen H, Mecklin JP, Moller P, Myrhoi T, Nagengast FM, Parc Y, Phillips R, Clark SK, de Leon MP, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen J. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008 May;57(5):704-13. doi: 10.1136/gut.2007.136127. Epub 2008 Jan 14. PMID 18194984
• BACKGROUNDBulow S, Bjork J, Christensen IJ, Fausa O, Jarvinen H, Moesgaard F, Vasen HF; DAF Study Group. Duodenal adenomatosis in familial adenomatous polyposis. Gut. 2004 Mar;53(3):381-6. doi: 10.1136/gut.2003.027771. PMID 14960520
• BACKGROUNDSpigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4. PMID 2571019