Videocapsule Endoscopy in Lynch Syndrome

Study Overview
=================
Brief Summary
-----------------
Background Lynch syndrome is caused by a pathogenic variant in one of the four Mismatch Repair genes (MMR): MLH1, MSH2/Epcam, MSH6, or PMS2. These pathogenic variants confer a higher risk of developing colorectal and other cancers, including small bowel cancer. The risk of developing a small bowel adenocarcinoma is about 100 times higher compared to individuals without Lynch syndrome, and the lifetime risk of small bowel cancer is estimated at 4,2%. The diagnosis of a small bowel cancer depends on videocapsule endoscopy (VCE). This device is swalled so that it can record images of the small bowel, which are then stored on a wearable device for about 8 hours. The capsule is then expelled in the feces while the images are transferred to a computer to be analysed. To date, there is conflicting evidence on the efficacy of small bowel cancer screening with VCE Rationale: this registry study will collect prospective data from patients with LS undergoing VCE Aim: evaluate the incidence of neoplastic and pre-neoplastic lesions in patients with LS during a VCE-based small bowel cancer screening study Design: this is a multicentric, observational study that analyzes data from diagnostic techniques already approved. Patients will not undergo diagnostic procedures beyond what would be recommended by clinical practice.

Detailed Description
-----------------
Background Lynch syndrome (LS) is caused by a pathogenic germline defect in one of the mismatch repair genes (MMR), namely MLH1, MSH2/Epcam, MSH6, or PMS2. Such pathogenic defects confer a higher risk of developing not only colorectal cancer but also small bowel cancer (SBC). Patients with LS have a lifetime risk of SMB of 4.2%, with a relative risk of >100, compared to the general population. Moreover, patients with LS may develop SBC at a younger age, compared to SBC in individuals without LS. The diagnostic standard for SBC is video capsule endoscopy (VCE). This consists in swallowing a pill with a camera inside. The VCE will record the images through the gastrointestinal tract and send them via Bluetooth to a wearable device for roughly 8 hours The capsule is then expelled with feces while the images are stored in a computer for later revision. Today, the data on the efficacy of a screening program for SBC in patients with LS is controversial. Rationale This register study will collect prospective data on the VCEs done on patients with LS Objective To estimate the incidence of neoplasia and preneoplastic lesions of the small bowel in patients with LS via VCE Design Multicentric observational study with the use of approved diagnostic devices. It will not modify the current standard of care. The study design will not mandate obligatory studies of further procedures besides those that are clinically approved. Population At least 10 subjects/year by each center (400 patients by study completion) Controindications to VCE Stenosis, obstructions, fistulas (suspected or known) Cardiac defibrillators or cardiac pace-makers. Dysphagia Inability to provide written informed consent. Pregnancy (suspected or known). Risks of VCE VCE retention is the most dreaded adverse events. The risk may vary between 1.5 and 21%. Allergic reactions may be possible due to the use of sticky electrodes on the skin. Study duration 10 years from January 2016. Confounders To date, not known. Data management All results will remain confidential. Clinical data may become available at scientific meetings or in published articles, but patient anonymity will always be maintained Statistics The incidence of neoplastic and preneoplastic lesions of the subjects included in the study will be estimated. The sample size was established on the basis of feasibility (10 subjects enrolled each year for each center in 10 years = 400 patients in total). The expected incidence of small bowel injury is approximately 5%. With 400 subjects it is possible to estimate the incidence with an accuracy of 2% estimated with a 95% confidence interval. Descriptive statistical variables (mean, standard deviation, median, etc.) will be evaluated on the collected data. Any relationships between these variables will be evaluated using inferential statistics (t-test, chi-squared, logistic regression analysis, multivariate analysis, etc.). Any relationship with a p-value less than 0.05 will be considered significant. Ethics The investigators declare that the study will be conducted in accordance with the ethical principles deriving from the Declaration of Helsinki and the current legislation on Observational Studies. Informed consent. All subjects will be informed of the purpose of the study, of the confidentiality of the personal data, and of the fact that this data may be subject to review, for study-related reasons, by authorized person other than the physician. It will be emphasized that participation is entirely voluntary and that the patient can refuse further participation in the protocol at any time without affecting the patient's subsequent care. Informed consent will be obtained for all subjects included in the study prior to their inclusion in the present study, in accordance with national and local regulations.

Official Title
-----------------
Role of Videocapsule Endoscopy in Lynch Syndrome: a Multicenter Italian Registry Study

Conditions
-----------------
Lynch Syndrome, Lynch Syndrome I, Lynch Syndrome II, MLH1 Gene Mutation, MSH2 Gene Mutation, MSH6 Gene Mutation, PMS2 Gene Mutation, Small Bowel Adenocarcinoma

Intervention / Treatment
-----------------
* Device: Video capsule endoscopy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathogenic germline variant in one of the MMR genes (MLH1, MSH2/Epcam, MSH6, or PMS2). Exclusion Criteria: Patients younger than 18 years of age Patients unwilling or unable to provide informed consent Patients with prior small bowel surgery Patients with a contraindication to VCE

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lynch Syndrome<br>Video capsule endoscopy every 2 years | Device: Video capsule endoscopy<br>* Video capsule endoscopy every 2 years<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Small bowel adenocarcinoma | Annual incidence | 10 years | 
| Small bowel adenoma | Annual incidence | 10 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Videocapsule, Small bowel