Cancer risks for relatives of patients with serrated polyposis.

OBJECTIVES: Serrated polyposis (hyperplastic polyposis) is characterized by multiple polyps with serrated architecture in the colorectum. Although patients with serrated polyposis are known to be at increased risk of colorectal cancer (CRC) and possibly extracolonic cancers, cancer risk for their relatives has not been widely explored. The aim of this study was to estimate the risks of CRC and extracolonic cancers for relatives of patients with serrated polyposis. METHODS: A cohort of the 1,639 first- and second-degree relatives of 100 index patients with serrated polyposis recruited regardless of a family history of polyps or cancer from genetic clinics in Australia, New Zealand, Canada, and the USA, were retrospectively analyzed to estimate the country-, age-, and sex-specific standardized incidence ratios (SIRs) for relatives compared with the general population. RESULTS: A total of 102 CRCs were observed in first- and second-relatives (SIR 2.25, 95% confidence interval (CI) 1.75-2.93; P<0.001), with 54 in first-degree relatives (SIR 5.16, 95% CI 3.70-7.30; P<0.001) and 48 in second-degree relatives (SIR 1.38, 95% CI 1.01-1.91; P=0.04). Six pancreatic cancers were observed in first-degree relatives (SIR 3.64, 95% CI 1.70-9.21; P=0.003). There was no statistical evidence of increased risk for cancer of the stomach, brain, breast, or prostate. CONCLUSIONS: Our finding that relatives of serrated polyposis patients are at significantly increased risk of colorectal and pancreatic cancer adds to the accumulating evidence that serrated polyposis has an inherited component.

Immunohistochemical testing of conventional adenomas for loss of expression of mismatch repair proteins in Lynch syndrome mutation carriers: a case series from the Australasian site of the colon cancer family registry.

Debate continues as to the usefulness of assessing adenomas for loss of mismatch repair protein expression to identify individuals with suspected Lynch syndrome. We tested 109 polyps from 69 proven mutation carriers (35 females and 34 males) belonging to 49 Lynch syndrome families. All polyps were tested by immunohistochemistry for four mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. Detailed pathology review was performed by specialist gastrointestinal pathologists. The majority of polyps (86%) were conventional adenomas (n=94), with 65 tubular and 28 tubulovillous adenomas and a single villous adenoma. The remaining 15 lesions (14%) were serrated polyps. Overall, loss of mismatch repair expression was noted for 78/109 (72%) of polyps. Loss of mismatch repair expression was seen in 74 of 94 (79%) conventional adenomas, and 4 of 15 (27%) serrated polyps from mismatch repair gene mutation carriers. In all instances, loss of expression was consistent with the underlying germline mutation. Mismatch repair protein expression was lost in 27 of 29 adenomas with a villous component compared with 47 of 65 adenomas without this feature (93 vs 73%; P=0.028). A strong trend was observed for high-grade dysplasia. Mismatch repair deficiency was observed in 12 of 12 conventional adenomas with high-grade dysplasia compared with 60 of 79 with low-grade dysplasia (100 vs 76%; P=0.065). We were unable to demonstrate a significant association between conventional adenoma size or site and mismatch repair deficiency. All (4/4 or 100%) of the serrated polyps demonstrating mismatch repair deficiency were traditional serrated adenomas from a single family. Diagnostic testing of adenomas in suspected Lynch syndrome families is a useful alternative in cases where cancers are unavailable. The overwhelming majority of conventional adenomas from mutation carriers show loss of mismatch repair protein expression concordant with the underlying germline mutation.

Complications of tube thoracostomy placement in the emergency department.

BACKGROUND: Emergency medicine residents frequently perform invasive procedures, including tube thoracostomy (TT), that inherently place patients at risk for complications. OBJECTIVES: The purpose of the study was to assess the prevalence and types of complications from TT in an academic emergency department (ED). METHODS: A combined prospective and retrospective, observational study of all patients who had TT between December 2002 and January 2006 was performed. Exclusion criteria included age < 15 years and tube placement at an outside facility. Complications detected in the ED were defined as immediate, whereas those discovered later were defined as delayed. Complications requiring corrective surgical intervention, administration of blood products, or intravenous antibiotics were defined as major. Bivariate and multivariate analyses were used to identify operator and patient factors associated with complications. RESULTS: TTs were placed in 242 patients, and 90 (37%; 95% confidence interval [CI] 31.1-43.3%) experienced a complication. Major complications included one intercostal artery laceration, one retroperitoneal placement, and empyema in 2 patients. In multivariate analysis, blunt injury excluding motor vehicle accidents (odds ratio [OR] 2.57; 95% CI 1.27-5.21) and spontaneous pneumothorax (OR 3.84; 95% CI 1.80-8.18) were associated with all complications. TT size < 36 French and blunt injury excluding motor vehicle accidents were associated with immediate complications and spontaneous pneumothorax was associated with delayed complications. CONCLUSIONS: The vast majority of complications from TT in the ED were minor. The prevalence of complications was consistent with previous reports of TTs placed by non-emergency-medicine-trained physicians outside the ED. The findings can be used to identify avoidable complications and improve residency training.

Phenotypic diversity in patients with multiple serrated polyps: a genetics clinic study.

OBJECTIVE: Hyperplastic polyposis is a colonic polyposis condition of unknown aetiology. The purpose of this study was to examine the spectrum of phenotypic variation in patients with multiple serrated polyps as a basis for gene discovery. METHODS: One hundred and twenty-six patients with multiple (> or = 5) serrated polyps were recruited to the study. Polyp counts were extracted from histology and colonoscopy reports. Ethnicity was self-reported. Family history of cancer data were derived from pedigrees. Ascertainment status was classified as either index case or identified by screening. RESULTS: The average reported polyp count was 39. Patients with highest polyp numbers were more likely to be male (P = 0.02). Colorectal cancer (CRC) was identified in 49 of 119 patients (41%) and 28% of these patients had multiple CRC. Young onset patients had higher polyp numbers (P = 0.03) and were more likely to have their CRC in the distal colon (P = 0.02). CRC was significantly associated with the presence of adenomas (P = 0.03). Patients were divided into moderate polyposis (5-79 serrated polyps) and dense polyposis (80 or more) categories. The dense polyposis category was associated with a lack of family history for CRC (P = 0.034) and male gender (P = 0.014), independent of ascertainment status and recruitment site. CONCLUSION: Multiple serrated polyps were associated with an increased personal risk of CRC. A subset of patients with the highest polyp numbers was more likely to be male and to have no family history of CRC. This result suggests heterogeneous modes of inheritance and has implications for studies investigating the genetic basis of multiple serrated polyps.

Attitudes and practices regarding influenza vaccination among emergency department personnel.

In the United States, infections related to influenza result in a huge burden to the health care system and emergency departments (EDs). Influenza vaccinations are a safe, cost-effective means to prevent morbidity and mortality. We sought to understand the factors that contribute to the professional and personal influenza vaccination practices of health care workers in the ED setting by assessing their knowledge, attitudes, and practices with regards to the influenza vaccine. A cross-sectional study of all full-time ED staff (nurses, emergency medicine residents, and emergency medicine faculty) at an urban academic medical center in Boston treating > 90,000 ED patients annually, was performed. We examined knowledge, attitudes, and practices regarding personal influenza vaccination and support of an ED-based influenza vaccination program using an anonymous, self-administered questionnaire. Of 130 ED staff, 126 individuals completed the survey (97% response rate). Overall, 69% of respondents reported that they were very or extremely likely to be vaccinated before the coming influenza season. Residents (94%) and attending physicians (82%) were significantly more likely than nurses (42%) to be vaccinated (p < 0.001). Respondents likely to be vaccinated this year were more likely to support a vaccination program for ED patients (80% vs. 55% of those not vaccinated,p < 0.001). Providing regular education on the efficacy of preventive vaccination therapy and dispelling misconceptions regarding adverse effects may reduce barriers to vaccination programs. An educational initiative may result in acceptance of influenza vaccination by ED providers themselves, which could result in increased support for an influenza vaccination program for ED patients.

Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome).

Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

Risk factors for colorectal cancer in patients with multiple serrated polyps: a cross-sectional case series from genetics clinics.

BACKGROUND: Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps. METHODS AND FINDINGS: We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes. CONCLUSION: A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.

Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry.

PURPOSE: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. EXPERIMENTAL DESIGN: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. RESULTS: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor-negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. CONCLUSIONS: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.

Six-month follow-up of a brief intervention on self-reported safety belt use among emergency department patients.

OBJECTIVES: Safety belt use (SBU) reduces motor vehicle deaths by 45%. We previously reported that a brief intervention improved self-reported SBU among emergency department (ED) patients at 3 months. We sought to determine if these effects were sustained at 6 months postenrollment. METHODS: This was a prospective, randomized controlled trial of adult patients (age > or = 21 years) at an academic medical center ED from February 2006 to May 2006. Patients were systematically sampled for self-reported SBU. Those with self-reported SBU less than "always" were asked to participate. Subjects were surveyed at baseline with a nine-item series of situational SBU questions scored on a five-point Likert scale (e.g., 5 = always, 1 = never). This nine-item average comprised the mean SBU score. Subjects were randomized to a control group (CG) and an intervention group (IG). The CG received an injury prevention brochure; the IG received a brief motivation interview by a trained interventionist and the brochure. Subjects were phoned at 3 and 6 months to determine interval change in SBU scores via a standard script. Repeated-measures analysis of covariance and t-tests were used to analyze trends in mean SBU scores between groups, as well as to test mean changes in SBU scores from the 3- to 6-month intervals. RESULTS: Of 432 eligible patients, 292 enrolled (mean age = 35 years, SD +/- 11.2 years; 61% male). At baseline, there were no significant demographic differences; the IG (n = 147) and CG (n = 145) had similar mean SBU scores (2.8 vs. 2.6, p = 0.31), and 66% (n = 96 in each) completed both 3- and 6-month follow-up. The mean SBU score at 6 months in the IG was greater than in the CG group (3.6 vs. 2.9, p < 0.001), as were the mean SBU score differences from baseline (IG = 0.84 vs. CG = 0.29, p < 0.001). These differences were sustained from the 3-month interval (IG = -0.02 vs. CG = -0.06, p > 0.05). CONCLUSIONS: The previously reported finding that ED patients who received a brief motivation interview reported higher SBU scores at 3 months compared to a CG was sustained at 6-month follow-up. Although limited by self-report, a brief intervention may enhance lasting SBU behavior among high-risk ED patients.

Brief motivational intervention to increase self-reported safety belt use among emergency department patients.

OBJECTIVES: Brief motivational interventions have shown promise in reducing harmful behaviors. The authors tested an intervention to increase safety belt use (SBU) among emergency department (ED) patients. METHODS: From February 2006 to May 2006, the authors conducted a randomized trial of adult ED patients at a teaching hospital in Boston. ED patients were systematically sampled for self-reported SBU. Those with SBU other than "always" were asked to participate. At baseline, participants answered a 9-item series of situational SBU questions, each scored on a 5-point Likert scale. SBU was defined as a continuous variable (9-item average) and as a dichotomous variable (response of "always" across all items). Participants were randomized to an intervention or a control group. The intervention group received a 5- to 7-minute intervention, adapted from classic motivational interviewing techniques, by a trained interventionist. Participants completed a 3-month follow-up phone survey to determine changes from baseline SBU. Continuous and dichotomous SBU were analyzed via analysis of covariance and chi-square testing. RESULTS: Of 432 eligible patients, 292 enrolled (mean age 35 years, standard deviation [SD] +/-11 years; 61% male). At baseline, the intervention and control groups had similar mean (+/-SD) SBU scores (2.8 [+/-1.1] vs. 2.6 [+/-1.1], p = 0.31) and SBU prevalence (each 0%). At 3 months, 81% completed follow-up. The intervention group had significantly greater improvement in mean (+/-SD) SBU scores than controls (0.76 [+/-0.91] vs. 0.34 [+/-0.88], p < 0.001). Also, SBU prevalence of "always" was higher for the intervention group than controls (14.4% vs. 5.9%, p = 0.03). CONCLUSIONS: Participants receiving a brief motivational intervention reported higher SBU at follow-up compared to controls. An ED-based intervention may be useful to increase SBU.