Shortened surveillance intervals following suboptimal bowel preparation for colonoscopy: Results of a national survey

Purpose: Suboptimal bowel preparation can result in decreased neoplasia detection, shortened surveillance intervals, and increased costs. We assessed bowel preparation recommendations and the relationship to self-reported proportion of suboptimal bowel preparations in practice; and evaluated the impact of suboptimal bowel preparation on colonoscopy surveillance practices. A random sample of a national organization of gastroenterologists in the U.S. was surveyed. Methods: Demographic and practice characteristics, bowel preparation regimens, and proportion of suboptimal bowel preparations in practice were ascertained. Recommended follow-up colonoscopy intervals were evaluated for optimal and suboptimal bowel preparation and select clinical scenarios. Results: We identified 6,777 physicians, of which 1,354 were randomly selected; 999 were eligible, and 288 completed the survey. Higher proportion of suboptimal bowel preparations/week (≥10 %) was associated with hospital/university practice, teaching hospital affiliation, greater than 25 % Medicaid insured patients, recommendation of PEG alone and sulfate-free. Those reporting greater than 25 % Medicare and privately insured patients, split dose recommendation, and use of MoviPrep® were associated with a less than 10 % suboptimal bowel preparations/week. Shorter surveillance intervals for three clinical scenarios were reported for suboptimal preparations and were shortest among participants in the Northeast who more often recommended early follow-up for normal findings and small adenomas. Those who recommended 4-l PEG alone more often advised less than 1 year surveillance interval for a large adenoma. Conclusions: Our study demonstrates significantly shortened surveillance interval recommendations for suboptimal bowel preparation and that these interval recommendations vary regionally in the United States. Findings suggest an interrelationship between dietary restriction, purgative type, and practice and patient characteristics that warrant additional research

Gastroenterologists' Perceived Barriers to Optimal Pre-Colonoscopy Bowel Preparation: Results of a National Survey

Poor quality bowel preparation has been reported in almost one third of all colonoscopies. To better understand factors associated with poor bowel preparation, we explored perceived patient barriers to optimal pre-colonoscopy bowel preparation from the perspective of the gastroenterologist. A random sample of physician members of the American College of Gastroenterology was surveyed via the internet and postal mailing. Demographic and practice characteristics and practice-related and perceived patient barriers to optimal bowel preparation were assessed among 288 respondents. Lack of time, no patient education reimbursement, and volume of information were not associated with physician level of suboptimal bowel preparation. Those reporting greater than or equal to 10 % suboptimal bowel preparations were more likely to believe patients lack understanding of the importance of following instructions, have problems with diet, and experience trouble tolerating the purgative. Bowel preparation instruction communication and unmet patient educational needs contribute to suboptimal bowel preparation. Educational interventions should address both practice and patient-related factors

Split dose and MiraLAX-based purgatives to enhance bowel preparation quality becoming common recommendations in the US

Objectives: Rates of suboptimal bowel preparation up to 30% have been reported. Liberalized precolonoscopy diet, split dose purgative, and the use of MiraLAX-based bowel preparation (MBBP) prior to colonoscopy are recently developed measures to improve bowel preparation quality but little is known about the utilization prevalence of these measures. We examined the patterns of utilization of these newer approaches to improve precolonoscopy bowel preparation quality among American gastroenterologists. Methods: Surveys were distributed to a random sample of members of the American College of Gastroenterologists. Participants were queried regarding demographics, practice characteristics, and bowel preparation recommendations including recommendations for liberal dietary restrictions, split dose purgative, and the use of MBBP. Approaches were evaluated individually and in combination. Results: Of the 999 eligible participants, 288 responded; 15.2% recommended a liberal diet, 60.0% split dose purgative, and 37.4% MBBP. Diet recommendations varied geographically with gastroenterologists in the West more likely to recommend a restrictive diet (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.16–7.67) and physicians in the Northeast more likely to recommend a liberal diet more likely. Older physicians more often recommended split dosing (OR 1.04, 95% CI 1.04–2.97). Use of MBBP was more common in suburban settings (OR 2.14, 95% CI 1.23–3.73). Evidence suggests that physicians in private practice were more likely to prescribe split dosing (p = 0.03) and less often recommended MBBP (p = 0.02). Likelihood of prescribing MBBP increased as weekly volume of colonoscopy increased (p = 0.03). Conclusions: To enhance bowel preparation quality American gastroenterologists commonly use purgative split dosing. The use of MBBP is becoming more prevalent while a liberalized diet is infrequently recommended. Utilization of these newer approaches to improve bowel preparation quality varies by physician and practice characteristics. Further evaluation of the patterns of usage of these measures is indicated

Advantage of HSP110 (T17) marker inclusion for microsatellite instability (MSI) detection in colorectal cancer patients

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Microsatellite instability (MSI) is a genetic pathway leading to CRC, associated with particular clinicopathological features, and recently a major biomarker of immunotherapy response. There is little information the frequency MSI among Brazilian CRC patients, and it is still debatable the ideal methodology for MSI screening in countries with limited resources. We proposed to evaluate MSI by molecular and immunohistochemistry (IHC) methods, to compare both methodologies and also to assess the inclusion of a novel microsatellite marker, HSP110 (T17). The molecular MSI evaluation was performed using a PCR-multiplex panel in a total of 1013 CRC patients. Mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2) expression were evaluated by IHC. HSP110 (T17) marker was analyzed by fragment analysis. Molecularly, 89.5% of cases were MSI-negative and 10.5% were MSI-positive. The IHC showed that 88.9% of cases exhibited MMR-proficient status, 10.2% were MMR-deficient and 0.9% was inconclusive. Genotyping of the HSP110 (T17) in 106 MSI-positive and 215 MSI-negative cases showed its alteration only among the MSI-positive cases. We observed agreement (0.956, Kappa Test) between both molecular and IHC methodologies, with only eight discordant results, and in this subset of cases the HSP110 (T17) corroborate the molecular findings. This study suggests the use of molecular assays over IHC for MSI analysis and proposes the inclusion HSP110 (T17) marker as a complementary analysis in discordant cases.The present study was partially supported by a MCT/FINEP/CT-INFRA- PROINFRA 02/2010 grant.info:eu-repo/semantics/publishedVersio

Surveillance for pancreatic cancer in high-risk individuals

Background Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC

A Blood-Based Metabolomic Signature Predictive of Risk for Pancreatic Cancer

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the top 2.5th percentile have absolute 5-year risk estimates of \u3e13%. The risk prediction model based on circulating microbial and non-microbial metabolites provides a potential tool to identify individuals at high risk of PaCa that would benefit from surveillance and/or from potential cancer interception strategies

Attitude towards pre-implantation genetic diagnosis for hereditary cancer

The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition. Forty-eight Von Hippel-Lindau and 18 Li–Fraumeni Syndrome families were identified via the 9 family cancer clinics in the Netherlands. In total, 216 high risk family members and partners were approached, of whom 179 (83%) completed a self-report questionnaire. Of the high risk family members, 35% expressed a positive attitude towards PGD. Those with a current desire to have children were significantly more likely to have a positive attitude: 48% would consider the use of PGD. No other sociodemographic, medical or psychosocial variables were associated significantly with a positive attitude. The most frequently reported advantage of PGD is the avoidance of a possible pregnancy termination. Uncertainty about late effects was the most frequently reported disadvantage. These results indicate that approximately half of those contemplating a future pregnancy would consider the use of PGD. The actual uptake, however, is expected to be lower. There is no indication that psychosocial factors affect interest in PGD

A haplotype variation affecting the mitochondrial transportation of hMYH protein could be a risk factor for colorectal cancer in Chinese

<p>Abstract</p> <p>Background</p> <p>The human MutY homolog (<it>hMYH</it>), a DNA glycolsylase involved in the excision repair of oxidative DNA damage, is currently studied in colorectal cancer (CRC). We previously demonstrated a haplotype variant c.53C>T/c.74G>A of <it>hMYH </it>(T/A) increasing the risk for gastric cancer in Chinese. However, most investigations on correlation between <it>hMYH </it>and CRC are conducted in Western countries and the underlying mechanism has been poorly understood.</p> <p>Methods</p> <p>To determine whether the haplotype T/A variant of <it>hMYH </it>was related to colorectal carcinogenesis, we performed a case-control study in 138 colorectal cancer (CRC) patients and 343 healthy controls in a Chinese population. Furthermore, the C/G for wild-type, C/A or T/G for single base variant and T/A for haplotype variant <it>hMYH </it>cDNAs with a flag epitope tag were cloned into pcDNA3.1+ vector and transfected into cos-7 cell line. Their subcellular localizations were determined by immunofluorescence assay.</p> <p>Results</p> <p>It was found that the frequency of haplotype variant allele was statistically higher in CRC patients than that in controls (<it>P </it>= 0.02, odds ratio = 5.06, 95% confidence interval = 1.26 – 20.4). Similarly, significant difference of heterozygote frequency was indicated between the two groups (<it>P </it>= 0.019), while no homozygote was found. In addition, immunofluorescence analysis showed that hMYH protein with haplotype T/A variation presented in both nucleus and mitochondria, in contrast to the wild-type protein only converging in mitochondria. However, neither of the single missense mutations alone changed the protein subcelluar localization.</p> <p>Conclusion</p> <p>Although preliminarily, these results suggest that: the haplotype variant allele of <it>hMYH </it>leads to a missense protein, which partly affects the protein mitochondrial transportation and results as nuclear localization. This observation might be responsible for the increased susceptibility to cancers, including CRC, in Chinese.</p

MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer

Background: Approximately 10% of Lynch syndrome families have a mutation in MSH6 and fewer families have a mutation in PMS2. It is assumed that the cancer incidence is the same in families with mutations in MSH6 as in families with mutations in MLH1/MSH2 but that the disease tends to occur later in life, little is known about families with PMS2 mutations. This study reports on our findings on mutation type, cancer risk and age of diagnosis in MSH6 and PMS2 families. Methods: A total of 78 participants (from 29 families) with a mutation in MSH6 and 7 participants (from 6 families) with a mutation in PMS2 were included in the current study. A database of de-identified patient information was analysed to extract all relevant information such as mutation type, cancer incidence, age of diagnosis and cancer type in this Lynch syndrome cohort. Cumulative lifetime risk was calculated utilising Kaplan-Meier survival analysis. Results: MSH6 and PMS2 mutations represent 10.3% and 1.9%, respectively, of the pathogenic mutations in our Australian Lynch syndrome families. We identified 26 different MSH6 and 4 different PMS2 mutations in the 35 families studied. We report 15 novel MSH6 and 1 novel PMS2 mutations. The estimated cumulative risk of CRC at age 70 years was 61% (similar in males and females) and 65% for endometrial cancer in MSH6 mutation carriers. The risk of developing CRC is different between males and females at age 50 years, which is 34% for males and 21% for females. Conclusion: Novel MSH6 and PMS2 mutations are being reported and submitted to the current databases for identified Lynch syndrome mutations. Our data provides additional information to add to the genotype-phenotype spectrum for both MSH6 and PMS2 mutations