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Expert Review of Anticancer Therapy Jun 2024APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated... (Review)
Review
INTRODUCTION
APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers.
AREAS COVERED
The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices.
EXPERT OPINION
FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.
Topics: Humans; Adenomatous Polyposis Coli; Quality of Life; Colectomy; Postoperative Complications; Patient Care Team; Precision Medicine; Phenotype; Genotype; Fibromatosis, Aggressive
PubMed: 38785081
DOI: 10.1080/14737140.2024.2344649 -
International Journal of Molecular... Mar 2023Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic... (Review)
Review
Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic extra-intestinal manifestations. Patients affected will inevitably undergo abdominal surgery due to the malignant transformation of one or more adenomas. The pathogenesis of the disease is based on a loss of function mutation in adenomatous polyposis coli (APC), a tumor-suppressor gene, inherited following a Mendelian pattern. This gene is a key component of multiple cell functions that cooperate for homeostasis; when mutated, it contributes to the progression of colorectal adenoma into cancer. Recent studies have demonstrated that several additional mechanisms may influence this process, such as alterations in gut microbiota composition and mucosal barrier immunity, interaction with the immune microenvironment and inflammation, the hormone estrogen, and other signaling pathways. These factors represent promising targets of future therapies and chemoprevention, aiming to alter the progressive nature of the disease and improve the quality of life of families affected. Therefore, we performed a narrative review about the current knowledge of the aforementioned pathways involved in colorectal cancer pathogenesis in FAP, exploring the genetic and environmental factors that may contribute to the development of CRC in FAP.
Topics: Humans; Adenomatous Polyposis Coli Protein; Quality of Life; Adenomatous Polyposis Coli; Colorectal Neoplasms; Genes, APC; Adenoma; Carcinogenesis; Tumor Microenvironment
PubMed: 36982759
DOI: 10.3390/ijms24065687 -
Clinics in Colon and Rectal Surgery May 2024Familial adenomatous polyposis (FAP) is an autosomal dominant disorder affecting patients with germline mutations of the adenomatous polyposis coli (APC) tumor... (Review)
Review
Familial adenomatous polyposis (FAP) is an autosomal dominant disorder affecting patients with germline mutations of the adenomatous polyposis coli (APC) tumor suppressor gene. The surgical treatment of colorectal disease in FAP, which has the goal of colorectal cancer prevention, varies based on both patient and disease factors but can include the following: total colectomy with ileorectal anastomosis, proctocolectomy with stapled or hand-sewn ileal pouch-anal anastomosis, or total proctocolectomy with end ileostomy. The operative options and extent of resection, as well as the use of endoscopy and chemoprevention for the management of polyposis, will be discussed in detail in this article. In addition, commonly debated management decisions related to the treatment of patients with FAP, including the timing of prophylactic colorectal resections for patients with FAP and management of the polyp burden in the rectum, will be discussed. Finally, genotype considerations and the impact of desmoid disease on operative decisions in the setting of FAP will also be reviewed.
PubMed: 38617844
DOI: 10.1055/s-0043-1770732 -
The Lancet. Gastroenterology &... Jan 2024Gastrointestinal tract polyposis is characterised by the presence of multiple polyps, particularly in the colorectum, and encompasses both cancer predisposition genetic... (Review)
Review
Gastrointestinal tract polyposis is characterised by the presence of multiple polyps, particularly in the colorectum, and encompasses both cancer predisposition genetic syndromes and non-syndromic clinical manifestations. The sources of the heterogeneity observed in polyposis syndromes relate to genetic cause, mode of inheritance, polyp burden and histological type, and spectrum and frequency of extracolonic manifestations. These features determine the clinical management of carriers, including strategies for cancer prevention and early detection, and oncological treatments. Despite substantial progress in identifying the genetic causes of polyposis, a large proportion of cases remain genetically unexplained. Although some of these cases might be due to lifestyle, environmental factors, or cancer treatments, it is likely that additional polyposis predisposition genes will be identified. This Review provides an overview of the known syndromes and genes, genetic testing, and clinical management of patients with polyposis, and recent advances and challenges in the field of gastrointestinal polyposis.
Topics: Humans; Colorectal Neoplasms; Genetic Testing; Genetic Predisposition to Disease; Syndrome
PubMed: 37931640
DOI: 10.1016/S2468-1253(23)00240-6 -
Clinical Gastroenterology and... Apr 2016
Topics: Colonoscopy; Cyclooxygenase 2; Diarrhea; Histocytochemistry; Humans; Immunohistochemistry; Intestinal Polyposis; Laparoscopy; Male; Microscopy; Radiography, Abdominal; Rectal Neoplasms; Tomography, X-Ray Computed; Water-Electrolyte Imbalance
PubMed: 26370570
DOI: 10.1016/j.cgh.2015.09.001 -
The Journal of Pathology Feb 2018It is now well established that germline genomic aberrations can underlie high-penetrant familial polyposis and colorectal cancer syndromes, but a genetic cause has not... (Review)
Review
It is now well established that germline genomic aberrations can underlie high-penetrant familial polyposis and colorectal cancer syndromes, but a genetic cause has not yet been found for the major proportion of patients with polyposis. Since next-generation sequencing has become widely accessible, several novel, but rare, high-penetrant risk factors for adenomatous polyposis have been identified, all operating in pathways responsible for genomic maintenance and DNA repair. One of these is the base excision repair pathway. In addition to the well-established role of the DNA glycosylase gene MUTYH, biallelic mutations in which predispose to MUTYH-associated polyposis, a second DNA glycosylase gene, NTHL1, has recently been associated with adenomatous polyposis and a high colorectal cancer risk. Both recessive polyposis syndromes are associated with increased risks for several other cancer types as well, but the spectrum of benign and malignant tumours in individuals with biallelic NTHL1 mutations was shown to be broader; hence the name NTHL1-associated tumour syndrome. Colorectal tumours encountered in patients with these syndromes show unique, clearly distinct mutational signatures that may facilitate the identification of these syndromes. On the basis of the prevalence of pathogenic MUTYH and NTHL1 variants in the normal population, we estimate that the frequency of the novel NTHL1-associated tumour syndrome is five times lower than that of MUTYH-associated polyposis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Topics: Adenomatous Polyposis Coli; Animals; Biomarkers, Tumor; DNA Damage; DNA Glycosylases; DNA Repair; Deoxyribonuclease (Pyrimidine Dimer); Genetic Predisposition to Disease; Humans; Mutation; Mutation Rate; Penetrance; Phenotype; Risk Factors
PubMed: 29105096
DOI: 10.1002/path.5002 -
Gastroenterology Jun 2022The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and...
Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer.
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
Topics: Colorectal Neoplasms; Gastrointestinal Hemorrhage; Hamartoma; Hamartoma Syndrome, Multiple; Humans; Intestinal Polyposis; Intestinal Polyps; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome; Telangiectasia, Hereditary Hemorrhagic
PubMed: 35487791
DOI: 10.1053/j.gastro.2022.02.021 -
Gastrointestinal Endoscopy Clinics of... Apr 2023Polypectomy is the most common therapeutic endoscopic intervention in children. Management of sporadic juvenile polyps is limited to polypectomy to resolve symptoms,... (Review)
Review
Polypectomy is the most common therapeutic endoscopic intervention in children. Management of sporadic juvenile polyps is limited to polypectomy to resolve symptoms, whereas polyposis syndromes pose a multidisciplinary challenge with broader ramifications. In preparation for polypectomy, there are key patient, polyp, endoscopy unit, and provider characteristics that factor into the likelihood of success. Younger age and multiple medical comorbidities increase the risk of adverse outcomes, classified as intraoperative, immediate postoperative, and delayed postoperative complications. Novel techniques, including cold snare polypectomy, can significantly decrease adverse events but a more structured training process for polypectomy in pediatric gastroenterology is needed.
Topics: Humans; Child; Intestinal Polyposis; Colonic Polyps; Colonoscopy; Colorectal Neoplasms
PubMed: 36948756
DOI: 10.1016/j.giec.2022.11.001 -
The Korean Journal of Gastroenterology... Dec 2018Although small bowel the mainly occupies the most part of the gastrointestinal tract, small intestine tumors are rare, insidious in clinical presentation, and frequently... (Review)
Review
Although small bowel the mainly occupies the most part of the gastrointestinal tract, small intestine tumors are rare, insidious in clinical presentation, and frequently represent a diagnostic and management challenge. Small bowel tumors are generally classified as epithelial, mesenchymal, lymphoproliferative, or metastatic. Familial adenomatous polyposis and Peutz-Jeghers syndrome are the most common inherited intestinal polyposis syndromes. Until the advent of capsule endoscopy (CE) and device-assisted enteroscopy (DAE) coupled with the advances in radiology, physicians had limited diagnostic examination for small bowel examination. CE and new radiologic imaging techniques have made it easier to detect small bowel tumors. DAE allows more diagnosis and deeper reach in small intestine. CT enteroclysis/CT enterography (CTE) provides information about adjacent organs as well as pictures of the intestinal lumen side. Compared to CTE, Magnetic resonance enteroclysis/enterography provides the advantage of soft tissue contrast and multiplane imaging without radiation exposure. Treatment and prognosis are tailored to each histological subtype of tumors.
Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Capsule Endoscopy; Humans; Intestinal Neoplasms; Intestinal Polyps; Magnetic Resonance Imaging; Peutz-Jeghers Syndrome
PubMed: 30642146
DOI: 10.4166/kjg.2018.72.6.277 -
Klinicka Onkologie : Casopis Ceske a... 2019It is estimated that 5-10% of colorectal cancers arise due to a known genetic syndrome. Individuals with these cancer syndromes are also at risk of extracolonic cancers.... (Review)
Review
BACKGROUND
It is estimated that 5-10% of colorectal cancers arise due to a known genetic syndrome. Individuals with these cancer syndromes are also at risk of extracolonic cancers. Polyposis and nonpolyposis hereditary syndromes are generally recognized. Inclusion of next-generation sequencing technology, especially multiple-gene panel testing, in routine laboratory practice has made identifying the causes of these diseases significantly easier.
PURPOSE
To summarize current knowledge of the causes, clinical manifestations, diagnostic criteria, and recommendations for presymptomatic screening of individuals at risk of hereditary gastrointestinal polyposis and colorectal cancer syndromes. We dicuss currently defined syndromes detected by multiple-gene panel next-generation sequencing; these include constitutional mismatch repair deficiency (biallelic MLH1, MSH2, MSH6, PMS2 gene mutations), gastric adenocarcinoma and proximal polyposis of the stomach (APC gene), NTHL1-associated polyposis, polymerase proofreading-associated polyposis (POLD1, POLE genes), juvenile polyposis (SMAD4, BMPR1A genes), and serrated polyposis syndromes. Another aim is to summarize recent knowledge about well-known syndromes, including hereditary nonpolyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, MUTYH-associated polyposis, and Peutz-Jeghers and Cowden/PTEN hamartoma tumor syndromes.
CONCLUSION
Awareness of hereditary polyposis/colon cancer syndromes enables early diagnosis and prevention of cancer in affected individuals and their relatives. Genetic counseling, presymptomatic testing of at-risk individuals, and efficient screening may be beneficial for affected families. Thank to Lenka Foretová, M.D., PhD, (Masaryk Memorial Cancer Institute, Brno) for a critical review of the manuscript and valuable advices. The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 1. 3. 2019 Accepted: 6. 6. 2019.
Topics: Gastrointestinal Neoplasms; Genetic Testing; Humans; Neoplastic Syndromes, Hereditary
PubMed: 31409085
DOI: 10.14735/amko2019S97