Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis.
ABSTRACT MYH-associated polyposis (MAP) is a disorder caused by a bi-allelic germline MYH mutation, characterized by multiple colorectal adenomas. These adenomas typically harbor G:C-->T:A transversions in the APC and K-ras genes caused by MYH deficiency. Occasional hyperplastic polyps (HPs) have been described in MAP patients but a causal relationship has never been investigated. We examined the presence of HPs and sessile serrated adenomas (SSAs) in 17 MAP patients and studied the occurrence of G:C-->T:A transversions in the APC and K-ras gene in these polyps.
MAP patients were analyzed for the presence of HPs/SSAs. APC-mutation cluster region and K-ras codon 12 mutation analysis was performed in adenomas (n = 22), HPs (n = 63), and SSAs (n = 10) from these patients and from a control group of sporadic adenomas (n = 17), HPs (n = 24), and SSAs (n = 17).
HPs/SSAs were detected in 8 of 17 (47%) MAP patients, of whom 3 (18%) met the criteria for hyperplastic polyposis syndrome. APC mutations were detected only in adenomas and comprised exclusively G:C-->T:A transversions. K-ras mutations were detected in 51 of 73 (70%) HPs/SSAs in MAP patients, compared with 7 of 41 (17%) sporadic HPs/SSAs in the control group (P < .0001). In HPs/SSAs, 48 of 51 (94%) K-ras mutations showed G:C-->T:A transversions, compared with 2 of 7 (29%) sporadic HPs/SSAs in the control group (P < .0001).
HPs and SSAs are a common finding in MAP patients. The detection of almost exclusively G:C-->T:A transversions in the K-ras gene of HPs/SSAs strongly suggests that these polyps are related causally to MYH deficiency. This implies that distinct pathways, that is, APC-gene related in adenomas and nonrelated in HPS/SSAs, appear to be operational in MAP.
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ABSTRACT: Hereditary factors are involved in the development of a substantial proportion of all cases of colorectal cancer. Inherited forms of colorectal cancer are usually subdivided into polyposis syndromes characterized by the development of multiple colorectal polyps and nonpolyposis syndromes characterized by the development of few or no polyps. Timely identification of hereditary colorectal cancer syndromes is vital because patient participation in early detection programmes prevents premature death due to cancer. Polyposis syndromes are fairly easy to recognize, but some patients might have characteristics that overlap with other clinically defined syndromes. Comprehensive analysis of the genes known to be associated with polyposis syndromes helps to establish the final diagnosis in these patients. Recognizing Lynch syndrome is more difficult than other polyposis syndromes owing to the absence of pathognomonic features. Most investigators therefore recommend performing systematic molecular analysis of all newly diagnosed colorectal cancer using immunohistochemical methods. The implementation in clinical practice of new high-throughput methods for molecular analysis might further increase the identification of individuals at risk of hereditary colorectal cancer. This Review describes the clinical management of the various hereditary colorectal cancer syndromes and demonstrates the advantage of using a classification based on the underlying gene defects.Nature Reviews Gastroenterology & Hepatology 01/2015; DOI:10.1038/nrgastro.2014.229 · 10.81 Impact Factor
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ABSTRACT: To clarify the efficacy of proton pump inhibitors (PPIs) after endoscopic variceal obturation (EVO) with N-butyl-2-cyanoacrylate. A retrospective study was performed on 16 liver cirrhosis patients with gastric variceal bleeding that received EVO with injections of N-butyl-2-cyanoacrylate at a single center (Kyung Hee University Hospital at Gangdong) from January 2008 to December 2012. Medical records including patient characteristics and endoscopic findings were reviewed. Treatment results, liver function, serum biochemistry and cirrhosis etiology were compared between patients receiving PPIs and those that did not. Furthermore, the rebleeding interval was compared between patients that received PPI treatment after EVO and those who did not. The patient group included nine males and seven females with a mean age of 61.8 ± 11.7 years. Following the EVO procedure, eight of the 12 patients that received PPIs and three of the four non-PPI patients experienced rebleeding. There were no differences between the groups in serum biochemistry or patient characteristics. The rebleeding rate was not significantly different between the groups, however, patients receiving PPIs had a significantly longer rebleeding interval compared to non-PPI patients (22.2 ± 11.2 mo vs 8.5 ± 5.5 mo; P = 0.008). The duration of PPI use was not related to the rebleeding interval. A total of six patients, who had ulcers at the injection site, exhibited a shorter rebleeding interval (16.8 ± 5.9 mo) than patients without ulcers (19.9 ± 3.2 mo), though this difference was not statistically significant. PPI therapy can extend the rebleeding interval, and should therefore be considered after EVO treatment for gastric varices.
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ABSTRACT: Familial adenomatous polyposis (FAP) is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP). FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC), and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP.The Application of Clinical Genetics 01/2015; 8:95-107. DOI:10.2147/TACG.S51484