Familial Adenomatous Poliposys Italian Network (Rete Italiana Poliposi Adenomatosa Familiare)

RIPAF is a nationwide, multicenter, observational registry developed to address the current heterogeneity in the management of Familial Adenomatous Polyposis and related hereditary adenomatous polyposis syndromes in Italy. Although several specialized centers provide care for these patients, clinical practice varies in terms of genetic workup, surveillance protocols, timing and type of prophylactic surgery, and management of extracolonic manifestations. This fragmentation limits the possibility of conducting large-scale analyses and generating robust multicenter evidence.

The registry is designed to create a structured collaborative framework that integrates expertise from 28 participating institutions, enabling standardized data collection and long-term follow-up.

Study Population:

Eligible participants include pediatric and adult patients diagnosed with adenomatous colorectal polyposis, defined as more than 10 synchronous adenomas or at least 20 cumulative adenomas across colonoscopies. The registry encompasses:

APC-associated familial adenomatous polyposis (classic phenotype with >100 adenomas and attenuated phenotype with 10-99 adenomas); MUTYH-associated polyposis (biallelic pathogenic variants); Adenomatous polyposis associated with other susceptibility genes (e.g., POLE, POLD1, NTHL1, MSH3, GREM1); Polyposis cases without identified pathogenic variants (NAMP), provided adenomas represent the predominant histological type.

Patients with non-adenomatous polyposis syndromes (e.g., hamartomatous or serrated polyposis) are excluded.

Study Design and Data Collection:

This is an observational registry with both retrospective and prospective components. Each participating center defines its retrospective observation period according to local data availability, while prospective enrollment continues throughout the study duration.

Data are entered into a centralized, pseudonymized REDCap database hosted by the coordinating center. The infrastructure incorporates encrypted data storage, two-factor authentication, role-based access control, audit trails, and compliance with GDPR and Good Clinical Practice requirements. Direct identifiers remain stored locally at each participating institution and are not shared within the network.

Collected variables include:

Demographic characteristics (age class, sex, geographic region); Genetic data (genes tested, specific pathogenic variants, mutation location, testing date, family history); Clinical presentation at diagnosis (age, symptoms, polyp burden and distribution, histology, presence of colorectal cancer); Extracolonic manifestations (duodenal polyps with Spigelman stage, desmoid tumors, thyroid abnormalities, CNS tumors, other associated conditions); Surveillance data (colonoscopy and upper endoscopy intervals and findings); Surgical data (type of procedure-IRA versus IPAA-surgical approach, timing, indications, complications, functional outcomes); Oncological outcomes (colorectal and upper gastrointestinal cancers, staging, treatments, recurrence); Desmoid tumor management and outcomes; Follow-up information including vital status and cause of death; Quality-of-life measures when available.

Dates are recorded as time intervals from a reference date to ensure anonymization during data export.

Study Objectives:

The registry pursues three principal domains of investigation:

Natural History and Genotype-Phenotype Correlations:

Comprehensive evaluation of disease evolution across genetic subtypes, including age at onset, cancer incidence, extracolonic manifestations, and variability in clinical severity.

Prognostic and Therapeutic Determinants:

Analysis of overall and cancer-specific survival, impact of different surgical strategies (total colectomy with ileorectal anastomosis versus restorative proctocolectomy with ileal pouch-anal anastomosis), laparoscopic versus open approaches, incidence of rectal stump cancer, and outcomes of desmoid tumors following prophylactic surgery.

Quality-of-Care Assessment:

Measurement of time from symptoms to genetic diagnosis, adherence to surveillance protocols, timing of prophylactic surgery, and concordance between surgical management of probands and preventive interventions in relatives.

Governance and Quality Assurance:

The network is supervised by a Steering Committee, supported by multidisciplinary scientific and data management committees. Built-in validation rules, automated consistency checks, and periodic data cleaning procedures ensure data reliability. Each center accesses only its own patient data, while the coordinating center can analyze the full pseudonymized dataset without access to direct identifiers.

Sample Size and Timeline:

The estimated target population is approximately 1,500-2,000 patients based on the census of participating centers. The initial project duration is 36 months, encompassing ethics approvals, database development, retrospective data entry, prospective enrollment, interim analysis, and dissemination of results. The registry infrastructure is intended to remain operational beyond the initial funding period to enable extended follow-up.

Clinical and Scientific Impact:

By integrating clinical, genetic, surgical, and outcome data within a single national platform, RIPAF aims to:

Reduce variability in clinical management; Improve risk stratification and personalization of care; Benchmark surgical and oncological outcomes; Facilitate case discussion and knowledge exchange among centers;

Provide a foundation for national and international collaborative research, including engagement with European reference networks.

The registry ultimately seeks to enhance survival, optimize preventive strategies, and improve quality of life for individuals affected by hereditary adenomatous polyposis syndromes.