Reyad Al-Ghnaniem

Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study.

BACKGROUND & AIMSnLow folate intake may increase risk for colorectal cancer by inducing DNA hypomethylation. This study reports the influence of folate status, DNA methylation, and polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677C-->T and 1298A-->C), methionine synthase (MS 2756A-->G), and cystathionine-beta-synthase (CBS 844ins68) on risk for developing colorectal neoplasia.nnnMETHODSnThirty-five patients with adenoma, 28 patients with cancer, and 76 controls were recruited for a case control study. Recruitment consent rate was 98%. Blood samples were obtained for determination of blood folates, vitamin B(12), homocysteine, DNA methylation, and genotypes. Tissue biopsy samples were obtained at colonoscopy for determination of DNA methylation in colonic mucosa. Folate status was assessed by constructing a score from estimates of dietary intake and serum and erythrocyte folate.nnnRESULTSnCancer patients had 26% lower folate status (95% confidence interval [CI]: 6% to 44%, P = 0.01) and 21% lower serum vitamin B(12) concentration (95% CI: -38% to 1%, P = 0.06) compared with controls. [(3)H] methyl incorporation into colonic DNA was 26% higher in patients with adenoma (95% CI: 8% to 56%, P = 0.009) and 30% higher in patients with cancer (95% CI: -3% to 48%, P = 0.08) compared with controls. High folate status was associated with decreased risk for cancer (P = 0.01 for trend). Colonic and leukocyte DNA hypomethylation were associated with increased risk for adenoma (P = 0.02 and P = 0.01 for trend, respectively) and a nonsignificantly increased risk for cancer (P = 0.09 and P = 0.08 for trend, respectively).nnnCONCLUSIONSnLow folate status and DNA hypomethylation are associated with colorectal neoplasia.

Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma

Background and aims: A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia. The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a randomised, double blind, placebo controlled, parallel design. Methods: Subjects were randomised to receive either 400 μg/day folic acid supplement (nu200a=u200a15) or placebo (nu200a=u200a16) for 10 weeks. Genomic DNA methylation, serum and erythrocyte folate, and plasma homocysteine concentrations were measured at baseline and post intervention. Results: Folic acid supplementation increased serum and erythrocyte folate concentrations by 81% (95% confidence interval (CI) 57–104%; p<0.001 v placebo) and 57% (95% CI 40–74%; p<0.001 v placebo), respectively, and decreased plasma homocysteine concentration by 12% (95% CI 4–20%; pu200a=u200a0.01 v placebo). Folic acid supplementation resulted in increases in DNA methylation of 31% (95% CI 16–47%; pu200a=u200a0.05 v placebo) in leucocytes and 25% (95% CI 11–39%; pu200a=u200a0.09 v placebo) in colonic mucosa. Conclusions: These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid.

Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer

DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C → T and 1298A → C), methionine synthase (MS 2756A → G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36–78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r=−0.573, P<0.001 and r=−0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=−0.311, P=0.01 and r=−0.356, P=0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively).

Meta-analysis suggests antibiotic prophylaxis is not warranted in low-risk patients undergoing laparoscopic cholecystectomy.

Although laparoscopic cholecystectomy is associated with a low incidence of wound infection antibiotic prophylaxis is still commonly used in low-risk patients undergoing this procedure. A review of the available evidence on infective complications in laparoscopic surgery concluded that antibiotic prophylaxis could be omitted1. A meta-analysis was performed to assess whether antibiotic prophylaxis reduced the risk of wound infection and other septic complications.

The Relationship between Gene-Specific DNA Methylation in Leukocytes and Normal Colorectal Mucosa in Subjects with and without Colorectal Tumors

CpG island methylation in the promoter regions of tumor suppressor genes has been shown to occur in normal colonic tissue and can distinguish between subjects with and without colorectal neoplasms. It is unclear whether this relationship exists in other tissues such as blood. We report the relationship between estrogen receptor gene (estrogen receptor α) methylation in leukocyte and normal colonic tissue DNA in subjects with and without colorectal neoplasia. DNA was extracted from frozen stored whole blood samples of 27 subjects with cancer, 30 with adenoma, 16 with hyperplastic polyps, and 57 disease-free subjects. DNA methylation in seven CpG sites close to the transcription start of estrogen receptor α was quantitated using pyrosequencing and expressed as a methylation index (average methylation across all CpG sites analyzed). Estrogen receptor α methylation in leukocyte DNA was compared with estrogen receptor α methylation in normal colonic mucosa DNA that had been previously determined in the same subjects. Estrogen receptor α was partially methylated (median, 4.3%; range, 0.0-12.6%) in leukocyte DNA in all subjects, with no significant difference between disease groups (P > 0.05). Estrogen receptor α methylation in leukocytes was 60% lower than estrogen receptor α methylation in normal colonic tissue (P < 0.001). Estrogen receptor α methylation in colonic tissue (P < 0.001) and smoking (P = 0.016) were determinants of estrogen receptor α methylation in leukocytes, independent of age, body mass index, gender, and disease status. In conclusion, there was a positive relationship between estrogen receptor α methylation in leukocytes and colonic tissue in subjects with and without colorectal tumors. However, unlike in colonic tissue, estrogen receptor α methylation in leukocytes was unable to distinguish between disease groups. (Cancer Epidemiol Biomarkers Prev 2009;18(3):922–8)

1% Hydrocortisone ointment is an effective treatment of pruritus ani: a pilot randomized controlled crossover trial

BackgroundPruritus ani (PA) is a common condition which is difficult to treat in the absence of obvious predisposing factors. There is paucity of evidence-based guidelines on the treatment of this condition. We examined whether 1% hydrocortisone ointment is an effective treatment for PA.Materials and methodsA pilot randomized, double-blind, placebo-controlled, crossover trial was carried out. Eleven patients consented to take part in the trial and ten completed the study. After a 2-week run-in period, patients with primary PA were randomly allocated to receive 1% hydrocortisone ointment or placebo for 2xa0weeks followed by the opposite treatment for a further 2-week period. There was a washout period of 2xa0weeks between treatments. The primary outcome measure was reduction in itch using a visual analogue score (VAS). The secondary outcome measures were improvement in quality of life measured using a validated questionnaire (Dermatology Life Quality Index, DLQI) and improvement in clinical appearance of the perianal skin using the Eczema Area and Severity Index (EASI) score.ResultsTreatment with 1% hydrocortisone ointment resulted in a 68% reduction in VAS compared with placebo (Pu2009=u20090.019), a 75% reduction in DLQI score (Pu2009=u20090.067), and 81% reduction in EASI score (Pu2009=u20090.01).ConclusionA short course of mild steroid ointment is an effective treatment for PA.

Surgical dexterity after a night out on the town

Background:u2003 This study examines the effect of alcohol intake on surgical dexterity immediately after and the morning after alcohol intake and minimal sleep deprivation by simulating a typical night out on the town.

Strategy to reduce the risk of positive pancreatic resection margin at pancreatico-duodenectomy

Background:u2003 The accuracy of histological assessment of frozen section (FS) of the pancreatic resection margin (PRM) at pancreatico‐duodenectomy can be improved by concurrent FS examination of a sample of the suspected pancreatic lesion.

Prediction of inflammation of the appendix at open and laparoscopic appendicectomy: findings and consequences.

OBJECTIVEnTo evaluate the accuracy of operative assessment of the condition of the appendix during laparoscopic and open appendicectomy, and to assess whether a normal-looking appendix should be excised routinely during a laparoscopic operation.nnnDESIGNnProspective study.nnnSETTINGnDistrict general hospital, UK.nnnSUBJECTSn387 patients who presented with signs and symptoms of appendicitis and underwent appendicectomy.nnnINTERVENTIONn63 patients (16%) were operated on laparoscopically, of whom 48 were female.nnnMAIN OUTCOME MEASURESnCorrelation of operative with histological findings.nnnRESULTSnThe positive predictive value of operative assessment was increased during the laparoscopic procedure in both male (94.4% to 100%) and female (78% to 88%) patients. Of 21 female patients whose appendixes looked normal at laparoscopy, 5 had other conditions (appendixes normal on histological examination) and 4 were inflamed.nnnCONCLUSIONnIn women of childbearing age a normal-looking appendix should be resected during laparoscopic appendicectomy unless another condition is obviously the cause of the signs and symptoms.