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Background: The significance of serrated lesions in inflammatory bowel disease (IBD) remains unclear. We aim to characterize synchronous and metachronous lesions in IBD patients with an index serrated polyp and compare them to sporadic subjects with SSP., Methods: Serrated lesions in patients with IBD were identified from a pathology database and, after review, were reclassified as hyperplastic (HP), sessile serrated (SSPs), or serrated polyps unclassifiable (SPU)., Results: One hundred thirty-four IBD patients were found to have 147 serrated polyps at index colonoscopy. SSPs were more likely to be located in the right colon: SSP (76.0%), SPU (41.7%) and HP (27.8%); P = 0.002. Synchronous multifocal visible dysplasia occurred more frequently in the SSP or SPU groups (44.5% and 66%) compared to the HP group (12%); P = 0.031. Among 13 IBD patients with index SSP followed over a median of 6 years, 61.5% developed metachronous visible dysplasia or additional SSPs. Larger index SSP size was associated with higher risk of developing subsequent visible dysplasia with a 10% increase for every 1 mm increase in size (HR = 1.1; P = 0.028), but was not associated with developing subsequent SSP (P = 0.50). The risk of subsequent SSP or visible dysplasia was no different between the IBD and non-IBD groups, but there was a trend suggesting SSP may be a marker of increased early risk of metachronous visible dysplasia in IBD patients., Conclusions: IBD patients with an index SSP and SPU have a heightened risk of synchronous multifocal visible dysplasia. Additionally, IBD patients with SSP may be at risk of early metachronous visible dysplasia.

Background: Germline mutations in SMAD4 and BMPR1A disrupt the transforming growth factor β signal transduction pathway, and are associated with juvenile polyposis syndrome. The effect of genotype on the pattern of disease in this syndrome is unknown. This study evaluated the differential impact of SMAD4 and BMPR1A gene mutations on cancer risk and oncological phenotype in patients with juvenile polyposis syndrome., Methods: Patients with juvenile polyposis syndrome and germline SMAD4 or BMPR1A mutations were identified from a prospectively maintained institutional registry. Medical records were reviewed and the clinical patterns of disease were analysed., Results: Thirty-five patients had germline mutations in either BMPR1A (8 patients) or SMAD4 (27). Median follow-up was 11 years. Colonic phenotype was similar between patients with SMAD4 and BMPR1A mutations, whereas SMAD4 mutations were associated with larger polyp numbers (number of patients with 50 or more gastric polyps: 14 versus 0 respectively). The numbers of patients with rectal polyps was comparable between BMPR1A and SMAD4 mutation carriers (5 versus 17). No patient was diagnosed with cancer in the BMPR1A group, whereas four men with a SMAD4 mutation developed gastrointestinal (3) or extraintestinal (1) cancer. The gastrointestinal cancer risk in patients with juvenile polyposis syndrome and a SMAD4 mutation was 11 per cent (3 of 27)., Conclusion: The SMAD4 genotype is associated with a more aggressive upper gastrointestinal malignancy risk in juvenile polyposis syndrome., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Context: Adequate serum 25-hydroxyvitamin D concentrations, [25(OH)D], are required for optimal bone health, and low levels are associated with chronic diseases., Objective: We investigated whether 41 candidate single nucleotide polymorphisms (SNPs) in vitamin D and calcium pathway genes (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR, and CASR) are associated with [25(OH)D] or modify the increase in [25(OH)D] from vitamin D3 supplementation., Design and Setting: Baseline and year 1 [25(OH)D] measurements from a randomized controlled trial conducted at 11 clinical centers in the United States., Participants: A total of 1787 healthy non-Hispanic white participants aged 45-75 years., Interventions: Vitamin D3 (1000 IU/d), calcium carbonate (1200 mg/d elemental), both, or placebo., Main Outcome Measures: Genotype main effects and interactions with vitamin D3 treatment estimated using multiple linear regression., Results: The baseline serum [25(OH)D] was 25.4 ± 8.7 ng/mL (mean ± SD). Associations with baseline levels were discovered for SNPs in CYP24A1 (rs2209314, rs2762939) and confirmed for SNPs in GC and CYP2R1. After 1 year, [25(OH)D] increased on average by 6.1 ± 8.9 ng/mL on vitamin D3 treatment and decreased by 1.1 ± 8.4 ng/mL on placebo. The increase in [25(OH)D] due to vitamin D3 supplementation was modified by genotypes at rs10766197 near CYP2R1, rs6013897 near CYP24A1, and rs7968585 near VDR., Conclusions: The increase in [25(OH)D] attributable to vitamin D3 supplementation may vary according to common genetic differences in vitamin D 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), and the vitamin D receptor (VDR) genes. These findings have implications for achieving optimal vitamin D status and potentially for vitamin D-related health outcomes.

Data regarding the association between folate status and risk of prostate cancer are sparse and conflicting. We studied prostate cancer occurrence in the Aspirin/Folate Polyp Prevention Study, a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between July 6, 1994, and December 31, 2006. Participants were followed for up to 10.8 (median = 7.0, interquartile range = 6.0-7.8) years and asked periodically to report all illnesses and hospitalizations. Aspirin alone had no statistically significant effect on prostate cancer incidence, but there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). In contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid-containing supplements vs natural sources of folate.

Background: Previous research suggests that the G315A single-nucleotide polymorphism in the ornithine decarboxylase (ODC) gene may be a genetic marker for risk of colorectal neoplasia and may also modify the association of aspirin use with risk., Methods: We tested these hypotheses among participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or to aspirin treatment (81 or 325 mg daily) and followed for 3 years for the occurrence of new adenomas. Genomic DNA from 973 subjects was analyzed for ODC genotype. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to test the association between ODC genotype and adenoma occurrence and interactions with aspirin treatment. All statistical tests were two-sided., Results: Of the 973 subjects, 54% were homozygous wild-type (GG), 7% were homozygous variant (AA), and 39% were heterozygous individuals; the allele frequencies varied statistically significantly by race and ethnicity. Among these subjects, the absolute risk of any adenoma was 45% and the risk of an advanced lesion was 10%. Overall, no association was found between ODC genotype and the occurrence of new adenomas, but genotype did modify the effect of aspirin on adenoma risk. Although aspirin treatment had no protective effect among subjects with a GG genotype, among subjects with at least one A allele, it was associated with statistically significant reduced risks of any adenoma (RR = 0.77, 95% CI = 0.63 to 0.95; P = .02, P(interaction) = .04) and of advanced lesions (RR = 0.51, 95% CI = 0.29 to 0.90; P = .02, P(interaction) = .02). Among subjects with at least one A allele, 40.8% who took aspirin versus 52.9% who took placebo developed adenomas; 7.1% versus 14.0% developed advanced lesions., Conclusion: ODC genotype may modify the response to aspirin treatment for colorectal adenoma prevention.

Background: Clinical trials have shown that calcium supplementation modestly decreases the risk of colorectal adenomas. However, few studies have examined the effect of calcium on the risk of different types of colorectal lesions or dietary determinants of this effect., Methods: Our analysis used patients from the Calcium Polyp Prevention Study, a randomized, double-blind, placebo-controlled chemoprevention trial among patients with a recent colorectal adenoma. Nine hundred thirty patients were randomly assigned to calcium carbonate (1200 mg/day) or placebo. Follow-up colonoscopies were conducted approximately 1 and 4 years after the qualifying examination. We used general estimating equation (GEE) and generalized linear regression analyses to compute risk ratios and 95% confidence intervals (CIs) to assess the effect of calcium treatment versus placebo on the risk of hyperplastic polyps, tubular adenomas, and more advanced lesions. Additionally, we used GEE analyses to compare the calcium treatment effects for various types of polyps with that for tubular adenomas. We also examined the interaction between calcium treatment and baseline intake of dietary calcium, fat, and fiber. All P values were obtained using Wald tests based on the corresponding models. All tests of statistical significance were two-sided., Results: The calcium risk ratio for hyperplastic polyps was 0.82 (95% CI = 0.67 to 1.00), that for tubular adenomas was 0.89 (95% CI = 0.77 to 1.03), and that for histologically advanced neoplasms was 0.65 (95% CI = 0.46 to 0.93) compared with patients assigned to placebo. There were no statistically significant differences between the risk ratio for tubular adenomas and that for other types of polyps. The effect of calcium supplementation on adenoma risk was most pronounced among individuals with high dietary intakes of calcium and fiber and with low intake of fat, but the interactions were not statistically significant., Conclusion: Our results suggest that calcium supplementation may have a more pronounced antineoplastic effect on advanced colorectal lesions than on other types of polyps.

We have evaluated a number of diluted and undiluted topical corticosteroid preparations in terms of vasoconstrictor potency, clinical efficacy and skin thinning effects. We conclude that, for the materials tested so far, an area under the curve measurement obtained from serial readings of the vasoconstrictor assay allows reasonably accurate predictions to be made concerning the relative clinical efficacy and skin thinning potential of these agents. If further work with a wide range of topical corticosteroids confirms our findings, the value of the vasoconstrictor assay as a predictive model will be enhanced.

Two series of tests have been performed in order to assess the vasoconstrictor potency of several diluted and undiluted proprietary corticosteroid preparations. Results showed that differences in concentration of a particular corticosteroid were not always reflected as significant differences in vasoconstrictor potency. A previous finding that Eumovate ointment exhibits early vasoconstrictor activity similar to that of Betnovate ointment was confirmed. The extemporaneous dilution of proprietary corticosteroid preparations remains a widespread but controversial habit. In addition, several proprietary products are represented by a range of dilutions of the same corticosteroid with each concentration targeted at a different segment of the market place. Recent work by our group has revealed some interesting results concerning the vasoconstrictor potency of both diluted and undiluted preparations (Gibson et al., 1982). The aim of this study was to extend the investigation to cover a number of widely used preparations.

Sera from twenty-three patients with primary or metastatic testicular tumours of germinal origin were tested for antibodies against teratocarcinoma-associated antigen(s), using an indirect immunofluorescence technique. Human and 129/Sv mouse sperm and mouse teratocarcinoma cell line 402 AX were used as target cells. A total of fifteen sera were identified as positive, six of them when tested against both sperm and tumour cells. Tail staining has been the most prevalent pattern of fluorescence on both human and murine spermatozoa. These observations suggest that antibody to a common teratoma-defined antigen(s) was detected in sera of patients with testicular tumours.

During the course of a controlled clinical study the patients' facial acne was assessed using a 0-10 visual-tactile grading system and by lesion counting. In addition, black-and-white photographs and colour slides were taken at each patient visit and subsequently assessed by a panel of three dermatologists. Scores obtained from each method of assessment were subjected to statistical analysis and correlations between the techniques were evaluated. We conclude that a well thought out clinical grading system is the best overall method as it provides a meaningful assessment with speed and reasonable accuracy.