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

NCT03346980 | Completed DMC

• 1 other identifier: SPIGELMAN-VALIDATE
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.).

Conditions

Familial Adenomatous Polyposes; Duodenal Polyposis; Duodenal Cancer

Keywords

Spigelman

Outcome Measures

Primary Outcomes (1)

• Inter-observer agreement of the Spigelman Score evaluated by expert endoscopists.

  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. Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points.

  1 week

Secondary Outcomes (3)

• Inter- and intra-observer agreement of the endoscopic sub-scores evaluated by expert endoscopists (the number of polyps and the size of these)

  1 week

• Intra-observer agreement of Spigelman Score evaluated by expert endoscopists.

  1 week

• Inter- and intra-observer agreement of the Spigelman Score and the endoscopic sub-scores evaluated by novices.

  1 week

Study Arms (1)

Familial adenomatous polyposis

The Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive familial adenomatous polyposis patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible.

Diagnostic Test: Esophagogastroduodenoscopy

Interventions

Esophagogastroduodenoscopy DIAGNOSTIC_TEST

All patients will be evaluated with both standard HD gastroscope and side-viewing duodenoscope; the latter to ensure proper visualization of the major papilla.

Familial adenomatous polyposis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive FAP patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Copenhagen University Hospital, Hvidovre: lead

Study Sites (1)

Copenhagen University Hospital Hvidovre

Hvidovre, Capital, 2650, Denmark

Location

Related Publications (3)

• Vasen 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 BACKGROUND

• Bulow 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 BACKGROUND

• Spigelman 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 BACKGROUND

MeSH Terms

Conditions

Adenomatous Polyposis Coli; Duodenal Neoplasms

Interventions

Endoscopy, Digestive System

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Duodenal Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• John G Karstensen

  MD, PhD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: November 20, 2017
• Study Start: December 1, 2017
• Primary Completion: January 23, 2020
• Study Completion: January 23, 2020
• Last Updated: February 13, 2020

Record last verified: 2020-02

Locations

DK (1)