BACKGROUND: Juvenile polyposis syndrome is a dominant GI polyposis syndrome defined by ≥5 GI juvenile polyps or ≥1 juvenile polyps with a family history of juvenile polyposis. Mutations in BMPR1A or SMAD4 are found in 50% of individuals. Hereditary hemorrhagic telangiectasia is a dominant disorder characterized by epistaxis, visceral arteriovenous malformations, and telangiectasias. Hereditary hemorrhagic telangiectasia is diagnosed when ≥3 criteria including clinical manifestations or a family history, are present. A juvenile polyposis–hereditary hemorrhagic telangiectasia overlap syndrome has previously been reported in 22% of patients with juvenile polyposis due to a SMAD4 mutation. OBJECTIVE: Our objective was to determine the prevalence and clinical manifestations of hereditary hemorrhagic telangiectasia by Curacao criteria in our juvenile polyposis SMAD4 patients. DESIGN, PATIENTS, AND SETTING: This was a cohort study of juvenile polyposis patients in our inherited colon cancer registries. Hereditary hemorrhagic telangiectasia manifestations were obtained from medical records, patient contact, and/or prospective hereditary hemorrhagic telangiectasia screening. The Curacao criteria was used for diagnosis of hereditary hemorrhagic telangiectasia (≥3 criteria diagnostic; 2 criteria suspect of). MAIN OUTCOME MEASURES: Prevalence and clinical manifestations of hereditary hemorrhagic telangiectasia in juvenile polyposis SMAD4 patients. RESULTS: Forty-one juvenile polyposis families were identified. Genetic testing was available for individuals within 18 families. SMAD4 mutations were found in 21 relatives in 9 families. Eighty-one percent of SMAD4 patients had hereditary hemorrhagic telangiectasia and 14% were suspected of having hereditary hemorrhagic telangiectasia. Epistaxis and asthma are the most common symptoms in our overlap patients. Symptomatic and subclinical arteriovenous malformations were noted near universally. LIMITATIONS: There was a single, tertiary referral center. CONCLUSIONS: Nearly all juvenile polyposis SMAD4 patients have the overlap syndrome. The clinical implications and need for hereditary hemorrhagic telangiectasia screening are important factors for genetic testing in juvenile polyposis. Health care providers must be cognizant of the juvenile polyposis–hereditary hemorrhagic telangiectasia overlap syndrome and the implications for management of these patients.

Release date: April 1, 2018Expiration date: March 31, 2019Estimated time of completion: 1 hourClick here to start this CME activity.Click here to complete post-test and CME certificate.ABSTRACTGallstones are common in the United States, affecting an estimated 1 in 7 adults. Fortunately, they are asymptomatic in up to 80% of cases, and current guidelines do not recommend cholecystectomy unless they cause symptoms. Laparoscopic cholecystectomy is the standard treatment for symptomatic gallstones, acute cholecystitis, and gallstone pancreatitis.

BACKGROUND: Adenoma detection rate is an important quality indicator. High adenoma detection rate is related to fewer interval cancers. Interval cancers arise from sessile serrated polyps, often in the proximal colon. The detection of adenomas and sessile serrated polyps by location may enhance colonoscopy efficacy. OBJECTIVE: The aim of this study was to determine entire colon and segmental adenoma and sessile serrated polyp detection rates and to assess the impact of endoscopist specialty on polyp detection. DESIGN: Colonoscopies performed by 65 multispecialty endoscopists were studied. SETTING: This study was conducted at an academic medical center. PATIENTS: Average-risk outpatients undergoing screening colonoscopy were selected. MAIN OUTCOME MEASURES: Polyp detection rates were determined by sex, colon segment, and each endoscopist. RESULTS: Included were 2167 patients. Adenoma and sessile serrated polyp detection rates were 25% and 2% and not significantly different by specialty of the endoscopist. The adenoma detection rate was higher in men (31%) than in women (20%), including each segment in the colon. It was higher proximally (20%) than distally (16%) (p = 0.027) in men, but no different in proximal (11%) and distal colon (11%) (p = 0.66) in women. Sessile serrated polyp detection was the same in men and women at 2% (p = 0.84) and 3-fold higher in the proximal than in the distal colon (1.4% vs 0.5%), but only significantly so in women (p = 0.041). We found a poor correlation between adenoma and sessile serrated polyp detection rates (r = 0.35). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Prevalent adenomas are detected more often in men than in women, including overall and by colon segment. The proximal adenoma detection rate is significantly higher than the distal adenoma detection rate in men, but segmental rates are similar in women. Sessile serrated polyp detection rates are low, albeit 3-fold higher in the proximal colon, and are found as frequently in men and women. High-quality colonoscopy, as evidenced by adenoma detection rate, varies by endoscopist but is independent of colonoscopist subspecialty.

BACKGROUND: Surveillance colonoscopy is recommended for patients with serrated polyps, but the risk of metachronous polyps is not well established. OBJECTIVE: The aim of this study was to determine the risk of metachronous polyps in patients with serrated polyps and assess the relationship of coexistent adenomas in polyp recurrence. DESIGN AND SETTING: This prospective cohort study was conducted in a single tertiary center in the United States. PATIENTS: Patients were included if they had a hyperplastic polyp ≥10 mm a sessile serrated polyp or a traditional serrated adenoma with or without coexistent adenomas, or only adenomas at baseline colonoscopy MAIN OUTCOME MEASUREMENTS: The cumulative incidence of advanced adenomas and advanced serrated polyps was the primary outcome measured. RESULTS: The incidence of metachronous advanced adenomas was highest in patients with baseline advanced adenoma (40%) and 10% in those with serrated polyps only. The coexistence of serrated polyps and adenomas did not increase the risk of metachronous advanced adenoma (27% in serrated polyps + advanced adenoma and 7% in serrated polyps + nonadvanced adenoma). Metachronous serrated polyps ≥10 mm were seen exclusively in patients with baseline serrated polyps (serrated polyps only, 7%; serrated polyps + nonadvanced adenoma, 11%; serrated polyps +advanced adenoma, 9%) and not in patients with only adenomas at baseline. LIMITATION: The small cohort and the data collected retrospectively were limitations of this study. CONCLUSIONS: Patients with baseline large hyperplastic polyps, sessile serrated polyps with or without dysplasia, or traditional serrated adenoma have a low risk of metachronous advanced adenoma, but were the sole group with recurrent large serrated polyps. No effect of coexistent serrated polyps and adenomas was seen for the recurrence of advanced adenoma.

Molecular studies suggest inhibition of colorectal mucosal polyamines (PAs) may be a promising approach to prevent colorectal cancer (CRC). Inhibition of ornithine decarboxylase (ODC) using low-dose eflornithine (DFMO, CPP-1X), combined with maximal PA export using low-dose sulindac, results in greatly reduced levels of normal mucosal PAs. In a clinical trial, this combination (compared with placebo) reduced the 3-year incidence of subsequent high-risk adenomas by >90 %. Familial Adenomatous Polyposis (FAP) is characterized by marked up-regulation of ODC in normal intestinal epithelial and adenoma tissue, and therefore PA reduction might be a potential strategy to control progression of FAP-related intestinal polyposis. CPP FAP-310, a randomized, double-blind, Phase III trial was designed to examine the safety and efficacy of sulindac and DFMO (alone or in combination) for preventing a clinically relevant FAP-related progression event in individuals with FAP. Eligible adults with FAP will be randomized to: CPP-1X 750 mg and sulindac 150 mg, CPP-1X placebo and sulindac 150 mg, or CPP-1X 750 mg and sulindac placebo once daily for 24 months. Patients will be stratified based on time-to-event prognosis into one of the three treatment arms: best (ie, longest time to first FAP-related event [rectal/pouch polyposis]), intermediate (duodenal polyposis) and worst (pre-colectomy). Stage-specific, “delayed time to” FAP-related events are the primary endpoints. Change in polyp burden (upper and/or lower intestine) is a key secondary endpoint. The trial is ongoing. As of February 1, 2016, 214 individuals have been screened; 138 eligible subjects have been randomized to three treatment groups at 15 North American sites and 6 European sites. By disease strata, 26, 80 and 32 patients are included for assessment of polyp burden in the rectum/pouch, duodenal polyposis and pre-colectomy groups, respectively. Median age is 40 years; 59 % are men. The most common reasons for screening failure include minimal polyp burden (n = 22), withdrawal of consent (n = 9) and extensive polyposis requiring immediate surgical intervention (n = 9). Enrollment is ongoing. This trial is registered at ClinicalTrials.gov ( NCT01483144 ; November 21, 2011) and the EU Clinical Trials Register( EudraCT 2012-000427-41 ; May 15, 2014).