Hereditary Gastrointestinal Polyposis Syndromes Research Articles

The histomorphological and molecular landscape of colorectal adenomas and serrated lesions.

SummaryThe 2019 WHO classification of digestive system tumors significantly reformed the classificatory definition of serrated lesions of the colorectal mucosa and added new essential diagnostic criteria for both conventional adenomas and hereditary gastrointestinal polyposis syndromes. Histopathological examination of colorectal adenocarcinoma precursors lesions represents an important segment of daily clinical practice in a pathology department and is essential for the implementation of current colorectal adenocarcinoma secondary prevention strategies. This overview will focus on a schematic histopathological and molecular classification of precursor lesions arising within colorectal mucosa.

Hereditary Polyposis Syndromes.

Colorectal cancer (CRC) is the third most common cancer in the USA and inherited cancer syndromes are responsible for approximately 3-5% of all CRCs. Genetic testing costs have plummeted in recent years; however, awareness and referral of high-risk patients for testing is still very low. We review the salient clinical features, genetics, and management of well-defined gastrointestinal (GI) hereditary polyposis syndromes including familial adenomatous polyposis, MUTYH-associated polyposis, and the hamartomatous polyposis syndromes. Comprehensive endoscopic surveillance has the potential to prevent the development of GI cancer and to identify early-stage cancer; newer developments like high-definition endoscopes, chromoendoscopy, and the use of cap-assisted endoscopy have shown promise for enhanced lesion detection rates. Several chemoprevention trials have yielded promising results but safety and efficacy data for long-term use is still awaited. Several new polyposis genes have also been identified in the recent years. Multiple societies have recently published updated surveillance guidelines to aid clinicians in the detection and management of patients with hereditary GI polyposis syndromes. Although these syndromes are rare, it is crucial for the clinicians to recognize these in a timely manner, for the appropriate management plans for both the patient and their at risk family members.

Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

ESGE recommends that individuals with hereditary gastrointestinal polyposis syndromes should be surveilled in dedicated units that provide monitoring of compliance and endoscopic performance measures. Strong recommendation, moderate quality of evidence, level of agreement 90 %.ESGE recommends performing esophagogastroduodenoscopy, small-bowel examination, and/or colonoscopy earlier than the planned surveillance procedure if a patient is symptomatic. Strong recommendation, low quality of evidence, level of agreement 100 %.

Colorectal polyps and polyposis syndromes.

A polyp is defined as any mass protruding into the lumen of a hollow viscus. Colorectal polyps may be classified by their macroscopic appearance as sessile (flat, arising directly from the mucosal layer) or pedunculated (extending from the mucosa through a fibrovascular stalk). Colorectal polyps may also be histologically classified as neoplastic or as non-neoplastic (hyperplastic, hamartomatous, or inflammatory). The neoplastic polyps are of primary importance because they harbor a malignant potential, which represents a stage in the development of colorectal cancer. For this reason, it is essential to identify these polyps at a sufficiently early stage, when a simple outpatient procedure to remove them can interrupt the development of colorectal cancer and prevent disease and death. When invasive carcinoma arises in a polyp, careful consideration must be given to ensuring the adequacy of treatment. Although most neoplastic polyps do not evolve into cancer, it is well accepted that the majority of colorectal carcinomas evolve from adenomatous polyps; the sequence of events leading to this transformation is referred to as the adenoma-to-carcinoma sequence.The presence of a systemic process that promotes the development of multiple gastro-intestinal polyps is termed ‘polyposis’. Hereditary gastro-intestinal polyposis syndromes account for approximately 1% of all cases of colorectal cancer and are associated with a broad spectrum of extra-colonic tumors. Early detection and accurate classification of these syndromes are essential, in order to initiate a surveillance program for the early detection of cancer. Several polyposis syndromes have been described, each having its own genetic basis and characteristic polyp distribution, clinical presentation, and malignancy risk.Diagnostic modalities and treatment options for neoplastic polyps—as well as the most prevalent polyposis syndromes—are reviewed below.

Hereditary Gastrointestinal Polyposis Syndromes: A Review Including Newly Identified Syndromes

There are multiple hereditary and non-hereditary polyposis syndromes that were originally categorized as adenomatous or hamartomatous. More recently, serrated polyps and their syndromes have been defined. Nearly all of these syndromes have a risk of colorectal cancer in the individuals and affected family members. Most of these syndromes are associated with extracolonic manifestations, including extracolonic tumors. The major clinical features, genetic mechanisms, and clinical management of Familial Adenomatous Polyposis (FAP), Peutz-Jeghers Syndrome (PJS), Juvenile Polyposis Syndrome (JPS), PTEN Hamartoma Syndrome (PTHS), and the more recently described syndromes MUTYH-Associated Polyposis, Hereditary Mixed Polyposis Syndrome, Serrated Polyposis Syndrome, and Polymerase Proofreading Associated Polyposis are summarized in this article.

Polyposissyndrome des Gastrointestinaltrakts

Hereditary gastrointestinal polyposis syndromes account for around 1% of all colorectal cancers; most of them are associated with a broad spectrum of extracolonic tumors. The initial diagnosis is based on endoscopic findings and polyp histology. Molecular genetic screening is important for the delineation of conditions with a similar phenotype such as autosomal dominant familial adenomatous polyposis (FAP) and autosomal recessive MUTYH-associated polyposis (MAP). Identification of the germline mutation in an affected person is a prerequisite for the exact evaluation of the recurrence risk in relatives and the predictive testing of asymptomatic persons at risk. Beside cases with attenuated adenomatosis or few colorectal adenomas, diagnostic difficulties are common among the hamartomatous polyposes such as the juvenile polyposis syndrome due to their broad clinical overlap and uncertainties in histological assessment. Several poorly defined nonhereditary polyposis syndromes and those with an as yet unknown etiology exist including hyperplastic polyposis syndrome. Early detection and accurate classification are essential since effective methods for surveillance and treatment are available.

The Differential Diagnosis and Early Detection of Hereditary Gastrointestinal Polyposis Syndromes

Survival times are often used to compare treatments. Survival data are a special type of data, and therefore have to be analyzed with special methods.We illustrate special techniques for analyzing survival times by applying them to a publication on the treatment of patients with brain tumors. The present article is based on textbooks of statistics, a selective review of the literature, and the authors' own experience.Survival times are analyzed with the Kaplan-Meier method, which yields two measures of interest: survival rates and the median survival time. The log-rank test is used to compare survival times across treatment groups. Cox regression is used in multivariable models. The hazard ratio, a descriptive measure for differences in survival times, is explained.If survival times are analyzed without the use of special techniques, or if the underlying assumptions are not taken into account, faulty interpretation may result. Readers of scientific publications should know these pitfalls and be able to judge for themselves whether the chosen analytical method is correct.

Gastrointestinal Polyposis Syndromes

Colorectal cancer is one of the leading causes of cancer-related death in the Western society, and the incidence is rising. Rare hereditary gastrointestinal polyposis syndromes that predispose to colorectal cancer have provided a model for the investigation of cancer initiation and progression in the general population. Many insights in the molecular genetic basis of cancer have emerged from the study of these syndromes. This review discusses the genetics and clinical manifestations of the three most common syndromes with gastrointestinal polyposis and an increased risk of colorectal cancer: familial adenomatous polyposis (FAP), juvenile polyposis (JP) and Peutz-Jeghers syndrome (PJS).

AN INTERNET BASED PEDIATRIC RESIDENT QUESTIONNAIRE ON KNOWLEDGE ON HEREDITARY GASTROINTESTINAL POLYPOSIS SYNDROMES

Background: Patients with hereditary gastrointestinal polyposis syndromes present usually in the first two decades of life with hematochezia (FAP, JP) or intestinal obstruction (PJS) or anemia. Patients at risk of polyposis syndromes require continued surveillance. Physicians taking care of children should be able to recognize and competently manage these patients including their need for referral for endoscopy. Herein we present our findings on US pediatric and medicine pediatrics residents familiarity with gastrointestinal polyposis syndromes based on an internet-administerd questionnaire. Methods: This study was exempt from IRB approval. The program directors at all 196 pediatric, medicine pediatric programs throughout the US were asked to allow their residents to participate in an anonymous internet based questionaire testing their practice on, and knowledge of polyposis syndromes in children; 43 sites consented. The questionnaire was forwarded to the residents as a hyperlinked interactive web-page by e-mail. Questions addressed clinical practice (2) and tested knowledge (15) based on information included in 2 out of 3 standard pediatric textbooks. Results: The respondents included 323 residents; 290 pediatric, 33 medicine-pediatrics. Medicine-pediatrics residents were more likely to inquire on family history of polyposis or early onset colorectal cancer during health care maintenance (HCM) visits (P = 0.02, 0.03) than pediatric residents. Most residents (91%) would refer newly diagnosed children with polyposis to genetic counselling. Factual knowledge on polyps and polyposis syndromes varied widely by syndrome (15% [FAP]-80% [PJS] correct) but not by year of training. Discussion: Our study suggests that a greater emphasis should be placed on resident education on the identification and correct management of gastrointestinal polyps and polyposis syndromes including inquiry on pertinent family history during HCM visits.

A Prospective Trial Comparing Wireless Capsule Endoscopy and Barium Contrast Series for Small Bowel Surveillance in Hereditary Polyposis Syndromes

Background: Capsule endoscopy has demonstrated its clinical utility in the evaluation of the small bowel and, accordingly, it has been suggested that it could be useful for the identification of small intestinal polyps in patients with polyposis syndromes. Objectives: To establish the effectiveness of wireless capsule endoscopy for detecting small bowel polyps in patients with hereditary gastrointestinal polyposis syndromes in comparison with barium contrast series. Patients and Methods: Consecutive patients with gastrointestinal polyposis syndromes were included. Small bowel follow-through series and capsule endoscopy were performed within one-week in a blind fashion. Number and location of polyps were analyzed. Results: Twenty-four patients with familial adenomatous polyposis (n = 20) or Peutz-Jeghers syndrome (n = 4) were included. Capsule endoscopy detected small bowel polyps in 7 out of 24 patients (29%), whereas barium contrast study identified small intestinal polyps in only 3 of these 7 patients. In the four remaining patients, all of them with familial adenomatous polyposis, polyps detected by the capsule but missed in radiographic series were located at either ileum (2 cases), jejunum (1 case) or duodenum (1 case). No procedure-related complication was observed in any patient. Conclusions: Wireless capsule endoscopy is a high accurate technique for the detection of small bowel polyps, and it represents a valuable alternative to barium contrast series in the surveillance of patients with hereditary gastrointestinal polyposis syndromes. Background: Capsule endoscopy has demonstrated its clinical utility in the evaluation of the small bowel and, accordingly, it has been suggested that it could be useful for the identification of small intestinal polyps in patients with polyposis syndromes. Objectives: To establish the effectiveness of wireless capsule endoscopy for detecting small bowel polyps in patients with hereditary gastrointestinal polyposis syndromes in comparison with barium contrast series. Patients and Methods: Consecutive patients with gastrointestinal polyposis syndromes were included. Small bowel follow-through series and capsule endoscopy were performed within one-week in a blind fashion. Number and location of polyps were analyzed. Results: Twenty-four patients with familial adenomatous polyposis (n = 20) or Peutz-Jeghers syndrome (n = 4) were included. Capsule endoscopy detected small bowel polyps in 7 out of 24 patients (29%), whereas barium contrast study identified small intestinal polyps in only 3 of these 7 patients. In the four remaining patients, all of them with familial adenomatous polyposis, polyps detected by the capsule but missed in radiographic series were located at either ileum (2 cases), jejunum (1 case) or duodenum (1 case). No procedure-related complication was observed in any patient. Conclusions: Wireless capsule endoscopy is a high accurate technique for the detection of small bowel polyps, and it represents a valuable alternative to barium contrast series in the surveillance of patients with hereditary gastrointestinal polyposis syndromes.

Counseling families with hereditary gastrointestinal polyposis syndromes.

Counseling for families with one of the hereditary polyposis and/or colon cancer syndromes can be offered by a number of different professional persons depending upon the emotional needs of the counselee. It is sometimes difficult to persuade at-risk persons in polyposis families to institute a medical surveillance plan with their physicians because of their reactions to knowledge (or lack of it) of the family diagnosis. Counseling may reveal both emotional and financial problems as deterrents to needed medical planning. Support organizations and explanatory literature are helpful in allaying fears and promoting compliance.

Hereditary gastrointestinal polyposis syndromes.

Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous types. Familial adenomatous polyposis coli (FAPC) is the prototype adenomatous polyposis syndrome and is defined by the autosomal dominant transmission of multiple (more than 100) colorectal adenomas. Virtually all affected patients develop colorectal carcinoma if untreated. Adenomas may develop also in the stomach and small bowel in FAPC patients, but the incidence of carcinoma in these sites is low. A variety of extracolonic manifestations has been reported in FAPC, with the name Gardner's syndrome applied to kindreds with osteomas of the skull and mandible, multiple epidermal cysts, and other skin and soft-tissue lesions. In Turcot's syndrome, brain tumors are present. The distinction between Gardner's and Turcot's syndromes and classical FAPC has become blurred because of marked overlap between them; some authorities consider them to be varying manifestations of a single genetic defect. The hamartomatous polyposes include Peutz-Jeghers syndrome, familial juvenile polyposis, Cowden's disease, intestinal ganglioneuromatosis, and the Ruvalcaba-Myrhe-Smith syndrome. The incidence of gastrointestinal cancer in patients with Peutz-Jeghers syndrome and familial juvenile polyposis exceeds that in the normal population, but is relatively low. In Cowden's disease, the gastrointestinal tract may be the site of multiple hamartomas, but there is no associated increase in the incidence of gastrointestinal cancers; instead, there is an increased incidence of carcinoma of the breast and thyroid. Intestinal ganglioneuromatosis occurs in von Recklinghausen's disease, in association with multiple endocrine neoplasia, type 2b, or as an isolated abnormality. Patients with ganglioneuromatosis do not appear to have an increased risk of developing gastrointestinal cancer. Ruvalcaba-Myrhe-Smith syndrome comprises macrocephaly, mental deficiency, an unusual craniofacial appearance, hamartomatous intestinal polyposis, and pigmented macules on the penis. No increased risk of developing cancer has been identified in the few reported cases.