Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, characterized by the development of hundreds to thousands of adenomas in the colorectum, with implications in children and adolescents. Almost all adult patients will develop colorectal cancer if they are not identified and treated early enough. Identifying and screening for FAP commences in adolescence. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the adenomatous polyposis (APC) gene. This European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) position paper provides a guide for diagnosis, assessment, and management of FAP in children and adolescents. This is the first position paper regarding FAP published by ESPGHAN. Literature from PubMed, Medline, and Embase was reviewed and in the absence of evidence, recommendations reflect the opinion of paediatric and adult experts involved in the care of polyposis syndromes. Because many of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, these of the recommendations are supported on expert opinion. This position paper will instruct on the appropriate management and timing of procedures in children and adolescents with FAP.

Keywords: adolescent; child; colonoscopy; colorectal cancer; familial adenomatous polyposis; polyposis

Importance

The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

Objective

The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

Design

An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology (SIGN), including the Delphi methodology and the AGREEII tool for quality assessment and external validation.

Results

The 38 consensus questions and 51 recommendations provide guidance on the following key aspects: I. More specific anatomic criteria for the definition of what qualifies as “ampullary” neoplasms, their distinction from duodenal and common bile duct tumors, and clinicopathologic characteristics of anatomic subsets; II. Avoidance of the confusing term “periampullary” for final classification; III. Refined definitions of intestinal, pancreatobiliary and mixed subtypes, and introduction of rare histologic subtypes; IV. The use and limitations of immunohistochemical and molecular profiling; V. Biopsy acquisition; VI. Clinical information required for accurate pathology assessment of biopsies and ampullectomy specimens; VII. Key items to be included in pathology reports of endoscopic specimens.

Conclusions and Relevance

Recognition of the Brescia PERIPAN guidelines will allow a more accurate classification of true ampullary cancers and their differentiation from other “periampullary” tumors. This will have significant implications for endoscopic interpretation and management, staging, pathologic diagnosis and therapeutic evaluation as well as oncologic treatment of various anatomic and histologic subsets of ampullary tumors. This will enhance the quality of both clinical care and future research in this complex medical field.

1 ESGE recommends that all duodenal adenomas should be considered for endoscopic resection as progression to invasive carcinoma is highly likely.
Strong recommendation, low quality evidence.

2 ESGE recommends performance of a colonoscopy, if that has not yet been done, in cases of duodenal adenoma.
Strong recommendation, low quality evidence.

3 ESGE recommends the use of the cap-assisted method when the location of the minor and/or major papilla and their relationship to a duodenal adenoma is not clearly established during forward-viewing endoscopy.
Strong recommendation, moderate quality evidence.

4 ESGE recommends the routine use of a side-viewing endoscope when a laterally spreading adenoma with extension to the minor and/or major papilla is suspected.
Strong recommendation, low quality evidence.

5 ESGE suggests cold snare polypectomy for small (< 6 mm in size) nonmalignant duodenal adenomas.
Weak recommendation, low quality evidence.

6 ESGE recommends endoscopic mucosal resection (EMR) as the first-line endoscopic resection technique for nonmalignant large nonampullary duodenal adenomas.
Strong recommendation, moderate quality evidence.

7 ESGE recommends that endoscopic submucosal dissection (ESD) for duodenal adenomas is an effective resection technique only in expert hands.
Strong recommendation, low quality evidence.

8 ESGE recommends using techniques that minimize adverse events such as immediate or delayed bleeding or perforation. These may include piecemeal resection, defect closure techniques, noncontact hemostasis, and other emerging techniques, and these should be considered on a case-by-case basis.
Strong recommendation, low quality evidence.

9 ESGE recommends endoscopic surveillance 3 months after the index treatment. In cases of no recurrence, a further follow-up endoscopy should be done 1 year later. Thereafter, surveillance intervals should be adapted to the lesion site, en bloc resection status, and initial histological result.
Strong recommendation, low quality evidence.

1 ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia.
Strong recommendation, high quality evidence.

ESGE/ESGAR do not recommend barium enema in this setting.
Strong recommendation, high quality evidence.

2 ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors.
Strong recommendation, low quality evidence.

ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete.
Weak recommendation, low quality evidence.

3 When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms.
Strong recommendation, high quality evidence.
Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation.
Very low quality evidence.

ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms.
Strong recommendation, high quality evidence.
In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms.
Weak recommendation, low quality evidence.

4 Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors.
Strong recommendation, high quality evidence.

ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer.
Weak recommendation, low quality evidence.

5 ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs.
Strong recommendation, moderate quality evidence.

ESGE/ESGAR also suggest the use of CCE in this setting based on availability.
Weak recommendation, moderate quality evidence.

6 ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasible
Weak recommendation, low quality evidence.

There is insufficient evidence to recommend CCE in this setting.
Very low quality evidence.

7 ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible.
Weak recommendation, low quality evidence.

There is insufficient evidence to recommend CCE in post-polypectomy surveillance.
Very low quality evidence.

8 ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation.

Strong recommendation, low quality evidence.

9 ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp >= 6 mm detected at CTC or CCE.
Follow-up CTC may be clinically considered for 6 – 9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia.

Strong recommendation, moderate quality evidence.