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Best Practice & Research. Clinical... 2022Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are rare inherited polyposis syndromes with a high colorectal cancer (CRC) risk. Therefore,... (Review)
Review
Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are rare inherited polyposis syndromes with a high colorectal cancer (CRC) risk. Therefore, frequent endoscopic surveillance including polypectomy of relevant premalignant lesions from a young age is warranted in patients. In FAP and less often in MAP, prophylactic colectomy is indicated followed by lifelong endoscopic surveillance of the retained rectum after (sub)total colectomy and ileal pouch after proctocolectomy to prevent CRC. No consensus is reached on the right type and timing of colectomy. As patients with FAP and MAP nowadays have an almost normal life-expectancy due to adequate treatment of colorectal polyposis, challenges in the management of FAP and MAP have shifted towards the treatment of duodenal and gastric adenomas as well as desmoid treatment in FAP. Whereas up until recently upper gastrointestinal surveillance was mostly diagnostic and patients were referred for surgery once duodenal or gastric polyposis was advanced, nowadays endoscopic treatment of premalignant lesions is widely performed. Aiming to reduce polyp burden in the colorectum as well as in the upper gastrointestinal tract, several chemopreventive agents are currently being studied.
Topics: Adenomatous Polyposis Coli; Adenomatous Polyps; Colorectal Neoplasms; Humans; Stomach Neoplasms
PubMed: 35988966
DOI: 10.1016/j.bpg.2022.101793 -
Terapevticheskii Arkhiv Mar 2019MutYH-associated polyposis is the only polyposis syndrome with an autosomal recessive type of inheritance, often phenotypically similar to a weakened form of familial... (Review)
Review
MutYH-associated polyposis is the only polyposis syndrome with an autosomal recessive type of inheritance, often phenotypically similar to a weakened form of familial adenomatous polyposis. For the development of the disease mutations in both alleles of the gene are required, but an increased risk of developing colorectal cancer in carriers of monoallelic mutations is noted. The diagnosis of MutYH-associated polyposis should be suspected in a patient with colorectal cancer over 45 years old on the background of polyps in the colon. The review presents modern algorithms for diagnostic and treatment of the disease.
Topics: Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Aged; Aged, 80 and over; Alleles; Colorectal Neoplasms; DNA Glycosylases; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Phenotype
PubMed: 31094179
DOI: 10.26442/00403660.2019.02.000124 -
Best Practice & Research. Clinical... 2022Serrated colorectal polyps, long considered innocent, are currently recognized as the precursors to one-third of all colorectal cancers (CRC). Serrated polyposis... (Review)
Review
Serrated colorectal polyps, long considered innocent, are currently recognized as the precursors to one-third of all colorectal cancers (CRC). Serrated polyposis syndrome (SPS), characterized by accumulation of multiple and/or large serrated polyps, symbolizes the highest expression of serrated pathway of carcinogenesis, leading to a high risk of CRC when it is not detected or treated on time. Although previously considered uncommon, SPS is now acknowledged as the most prevalent colorectal polyposis. This syndrome has attracted increasing interest over the past decade and has become a hot topic in the field of gastrointestinal oncology. Besides a small proportion of cases caused by germline mutations in RNF43, no clear genetic cause has been identified. Both epigenetic and environmental factors, especially smoking, have been related to this syndrome, but the etiology of SPS remains uncertain and diagnosis is based on endoscopic criteria. Recent studies on SPS have focused on identifying the underlying risk-factors for CRC, defining the best endoscopic techniques for surveillance and establishing optimal preventive strategies aimed at reducing CRC-incidence without exposing patients to unnecessary procedures. The purpose of this chapter is to review, from a practical perspective, current knowledge and future directions in the diagnosis and management of serrated polyposis syndrome.
Topics: Adenoma; Adenomatous Polyposis Coli; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans; Syndrome
PubMed: 35988960
DOI: 10.1016/j.bpg.2022.101791 -
Current Treatment Options in... Dec 2019Colorectal 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... (Review)
Review
PURPOSE OF REVIEW
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.
RECENT FINDINGS
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.
PubMed: 31705372
DOI: 10.1007/s11938-019-00251-4 -
Der Internist Feb 2021Gastrointestinal polyposis syndromes are the second most common cause of hereditary colorectal carcinomas after Lynch syndrome (hereditary non-polyposis colon cancer,... (Review)
Review
BACKGROUND
Gastrointestinal polyposis syndromes are the second most common cause of hereditary colorectal carcinomas after Lynch syndrome (hereditary non-polyposis colon cancer, HNPCC). The detection of a causal germline mutation in an affected family member serves for differential diagnosis, assessment of the recurrence risk and predictive testing of healthy individuals at risk.
OBJECTIVES
The present article aims to provide an overview of the differential diagnosis of different gastrointestinal polyposis syndromes based on the endoscopic findings, polyp histology, extraintestinal phenotype and molecular genetic diagnostics.
MATERIALS AND METHODS
The present article is based on a literature search on gastrointestinal polyposis syndromes.
RESULTS
In addition to familial adenomatous polyposis (FAP), there are further subtypes of adenomatous polyposis that can often only be distinguished by the detection of a causative germline mutation and are sometimes associated with different extracolonic manifestations. In hamartomatous polyposis syndromes, the clinical overlaps often cause differential diagnostic problems. Serratated polyposis syndrome is possibly the most frequent polyposis syndrome, although its cause is currently largely unexplained.
CONCLUSIONS
Early detection and correct classification of polyposis is crucial for adequate prevention and therapy. Access to multidisciplinary expert centres is useful for the care of families.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms; Early Detection of Cancer; Humans; Phenotype; Syndrome
PubMed: 33237439
DOI: 10.1007/s00108-020-00903-z -
Best Practice & Research. Clinical... 2022Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is... (Review)
Review
Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.
Topics: Colorectal Neoplasms; Gastrointestinal Neoplasms; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 35988962
DOI: 10.1016/j.bpg.2022.101799 -
Best Practice & Research. Clinical... 2022Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is... (Review)
Review
Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is associated in some patients with a different syndrome, Hereditary Hemorragic Telangiectasia, justifying a complementary and different management. Recent international recommendations help in managing this very rare disease, and this management should probably be restricted to expert centers able to take care of the multiple manifestations and risks of these patients and families. This paper will focus on the poorly known and evaluated aspects of juvenile polyposis, excluding the colonic involvement and epidemiology that are addressed in a different article of this issue.
Topics: Colon; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Smad4 Protein
PubMed: 35988968
DOI: 10.1016/j.bpg.2022.101802 -
Gastroenterology Clinics of North... Mar 2024Gastrointestinal polyposis disorders are a group of syndromes defined by clinicopathologic features that include the predominant histologic type of colorectal polyp and... (Review)
Review
Gastrointestinal polyposis disorders are a group of syndromes defined by clinicopathologic features that include the predominant histologic type of colorectal polyp and specific inherited gene mutations. Adenomatous polyposis syndromes comprise the prototypical familial adenomatous polyposis syndrome and other recently identified genetic conditions inherited in a dominant or recessive manner. Serrated polyposis syndrome is defined by arbitrary clinical criteria. The diagnosis of hamartomatous polyposis syndromes can be suggested from the histologic characteristics of colorectal polyps and the association with various extraintestinal manifestations. Proper identification of affected individuals is important due to an increased risk of gastrointestinal and extragastrointestinal cancers.
Topics: Humans; Colorectal Neoplasms; Adenomatous Polyposis Coli; Syndrome
PubMed: 38280747
DOI: 10.1016/j.gtc.2023.09.006 -
Frontline Gastroenterology Oct 2019Hereditary bowel tumours are usually part of a distinct syndrome which require management of both intestinal and extra-intestinal disease. Polyposis syndromes include:... (Review)
Review
Hereditary bowel tumours are usually part of a distinct syndrome which require management of both intestinal and extra-intestinal disease. Polyposis syndromes include: Familial adenomatous polyposis, MUTYH-associated polyposis, Serrated polyposis syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome and PTEN-hamartomatous syndromes. Of all colorectal cancers (CRC), 5%-10% will be due to an underlying hereditary CRC syndrome. Diagnosis and management of polyposis syndromes is constantly evolving as new scientific and technological advancements are made with respect to identifying causative genes and increased sophistication of endoscopic therapy to treat polyps. This, in addition to data yielded from meticulous record-keeping by polyposis registries has helped to guide management in what are otherwise relatively rare conditions. These data help guide clinical management of patients and their 'at-risk' relatives. Diagnosis is both genetic where possible but clinical recognition is key in the absence of an identifiable causative gene. Furthermore, some syndromes can overlap which can additionally complicate diagnosis. The principle goals of polyposis management are first to manage and treat the presenting patient and then to identify 'at-risk' patients, through screening and predictive genetic testing, endoscopic surveillance to allow therapy and guide surgical prophylaxis. Due to the complexity of diagnosis and management, patients and their families should be referred to a genetics centre or a polyposis registry where dedicated management can take place.
PubMed: 31656563
DOI: 10.1136/flgastro-2018-101053 -
World Journal of Gastroenterology Nov 2011Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk... (Review)
Review
Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.
Topics: Bone Morphogenetic Protein Receptors, Type I; Colon; Colorectal Neoplasms; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Polyps; Rectum; Smad4 Protein
PubMed: 22171123
DOI: 10.3748/wjg.v17.i44.4839