Senarath Edirimanne

Diabetes increases the risk of breast cancer: a meta-analysis

The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13-1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07-1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79-1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99-1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.

Is Sentinel Lymph Node Biopsy Necessary in Patients Undergoing Prophylactic Mastectomy? A Systematic Review and Meta‐Analysis

The gain by performing sentinel lymph node biopsy (SLNB) during prophylactic mastectomy (PM) is debatable, and we performed a meta‐analysis of existing literature to evaluate that the role of SLNB in subjects undergoing PM. A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science. The search identified 11 relevant articles reporting on patients who underwent SLNB at the time of PM. Data were abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI). We included 14 studies comprising of 2,708 prophylactic mastectomies. Among 2,708 prophylactic mastectomies, the frequency of occult invasive cancer (51 cases) was 1.8% and the rate of positive SLNs (33 cases) was 1.2%. In 25 invasive cancers at the time of PM were found to have negative SLNs which avoided axillary lymph node dissection (ALND). In seven cases with positive SLNBs were found not to have invasive cancer at the time of PM and needed a subsequent ALND. Most of the patients with positive SLNs had locally advanced disease in the contralateral breast. SLNB may be suitable for patients with ipsilateral, locally advanced breast cancer and is not recommend for all patients undergoing PM.

Colorectal complications of end-stage renal failure and renal transplantation: a review.

Aim  End‐stage renal failure (ESRF) and renal transplant recipients are thought to be associated with an increased risk of colorectal complications.

The extent of improvement of health-related quality of life as assessed by the SF36 and Paseika scales after parathyroidectomy in patients with primary hyperparathyroidism--a systematic review and meta-analysis.

BACKGROUND Previous studies have shown that parathyroidectomy for primary hyperparathyroidism (PHPT) improve the function and quality of life of patients. The aim of this systematic review and meta-analysis is to determine the health-related quality of life outcomes among those having surgical management for PHPT. METHODS Several databases were searched (MEDLINE, EMBASE, PubMed, Current Contents) for studies in which health-related quality of life was measured by reliable and validated instruments (SF-36 and Paseika Questionnaire) before and after parathyroidectomy for patients with primary hyperparathyroidism (PHPT). For the SF-36, score differences greater than 5 points indicate clinically relevant changes. RESULTS There were six studies with quality of life data. The SF-36 data was derived from 238 patients, with a mean age of 59 years and 71% were females. The range of follow up after surgery was 6 months to one year. The pre- and post-parathyroidectomy SF-36 quality of life scale scores were vitality (44 vs. 60, p<0.001), physical functioning (51 vs. 69, p<0.001), bodily pain (50 vs. 65, p<0.001), general health (54 vs. 64, p<0.001), role physical (34 vs. 52, p<0.001), role emotional (43 vs. 59, p<0.001), role social (60 vs. 74, p<0.001), and mental health (55 vs. 71, p<0.001). The Paseika data was derived from 203 patients, with a mean age of 54 years and 67% were females. The pre- and post-parathyroidectomy Paseika scores were feeling tired (51 vs. 19, p<0.001), feeling thirsty (29 vs. 12, p<0.001), mood swings (33 vs. 12, p<0.001), joint pains (32 vs. 14, p<0.001), irritability (31 vs. 10, p<0.001), feeling blue (31 vs. 14, p<0.001), feeling weak (37 vs. 15, p<0.001), itchy (17 vs. 7, p<0.001), forgetful (27 vs. 16, p<0.001), headache (18 vs. 5, p<0.001), abdominal pain (19 vs. 8, p<0.001), bone pain (38 vs. 17, p<0.001), ability to move off chair (27 vs. 11, p<0.001). CONCLUSION Parathyroidectomy significantly improves the short to medium-term health-related quality of life of patients suffering from primary hyperparathyroidism.

Recurrence and functional outcomes of partial adrenalectomy: A systematic review and meta-analysis

BACKGROUND Partial adrenalectomy is typically performed for the treatment of hereditary and sporadic bilateral tumours, to reduce the risk of adrenal failure, particularly in younger patients. Partial adrenalectomy proposes a postoperative steroid-free course nevertheless, is associated with the risk of local recurrence. In this study we evaluate the recurrence and functional outcomes of partial adrenalectomy. METHODS A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science. The search identified 60 relevant articles reporting on patients who underwent partial adrenalectomy. Data was extracted from each study and used to calculate a pooled event rate and 95% confidence interval (95% CI). RESULTS The overall recurrence rate was 8% (95% CI: 0.05-0.12) and the 85% (95% CI: 0.78-0.9) of the patients were steroid free. The recurrence rates were the least in the retroperitoneoscopic group 1% (95% CI: 0-0.04) and Conns syndrome group 2% (95% CI: 0.01-0.05) and highest in open group 15% (95% CI: 0.07-0.28) and Pheochromocytoma group 10% (95% CI: 0.07-0.16). Steroid independence rates were best in the Conns syndrome group 97% (95% CI: 0.85-0.99) and laparoscopic group 88% (95% CI: 0.75-0.95). CONCLUSIONS Partial adrenalectomy can obviate the need for steroid replacement in the majority of patients and local recurrence rates appear to be infrequent. For patients with hereditary and bilateral adrenal tumours, partial adrenalectomy should be recommended as a primary surgical approach whenever possible.

Deodorant Use and Breast Cancer Risk

To the Editor:The effect of deodorant use on breast cancer development has generated considerable interest in both the scientific community and the mainstream media. Primary observational studies and numerous reviews have been undertaken, investigating the effect of regular deodorant use on breast c

Delays in discharge of vascular surgical patients: a prospective audit

Aim:  To quantify delays in discharge for vascular surgical patients and identify causes of such delays.

Novel single-nucleotide polymorphisms in the calsequestrin-1 gene are associated with Graves’ ophthalmopathy and Hashimoto’s thyroiditis

Background The eye disorder associated with Graves’ disease, called Graves’ ophthalmopathy (GO), greatly reduces the quality of life in affected patients. Expression of the calsequestrin (CASQ1) protein in thyroid tissue may be the trigger for the development of eye muscle damage in patients with GO. We determined the prevalence of rs74123279, rs3747673, and rs2275703 single-nucleotide polymorphism (SNPs) in patients with autoimmune thyroid disorders, GO, Graves’ hyperthyroidism (GH), or Hashimoto’s thyroiditis (HT) and control subjects with no personal or family history of autoimmune thyroid disorders. Furthermore, we measured the concentration of the CASQ1 protein in normal and Graves’ thyroid tissue, correlating levels with parameters of the eye signs, CASQ1 antibody levels, and the CASQ1 gene polymorphism rs74123279 and rs2275703. Methods High-quality genomic DNA was isolated from fresh blood samples, assayed for identification of rs74123279, rs3747673, and rs2275703 SNPs in CASQ1 gene by MassARRAY SNP analysis using iPLEX technology of SEQUENOM. Results DNA samples from 300 patients and 106 control subjects (100 males, 306 females) with GO (n=74), GH (n=130), HT (n=96) and control subjects (n=106) were genotyped for the SNPs rs74123279, rs3747673 (n=405), and rs2275703 (n=407). The SNP rs74123279, rs3747673, and rs2275703 were identified as 1) common homozygous or wild type, 2) heterozygote, and 3) rare homozygous. Minor allele frequency for rs74123279, rs3747763, and rs2275703 were 21%, 40%, and 44%, respectively. Multiple comparisons of genotype frequency for rs74123279, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed P=0.06, 0.641, and 0.189, respectively. These results were substantiated by multiple comparison of alleles frequency for rs74123279, rs3838216, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed, P=0.36, 0.008, 0.66, and 0.05, respectively. Pairwise analysis of alleles frequency distribution in patients with GO showed significant probability for rs2275703, P=0.008. Conclusion Based on their evolutionary conservation and their significant prevalence, we suggest that CASQ1 gene SNPs rs74123279, rs3838216, and rs2275703 may be considered as genetic markers for GO.

Abstract P1-11-01: Physical Activity Reduces the Risk of Breast Cancer

Background: Lifestyle has been shown to significantly effect breast cancer incidence evident in the increased risk associated with obesity, diabetes, cigarettes and alcohol. The aim of this meta-analysis was to investigate the effect of two traditionally “beneficial” lifestyle choices: physical activity and weight loss. Specifically, we aimed to investigate the effect of the timing, intensity and duration of exercise on breast cancer incidence in women classified as either normal risk or increased risk. Finally, we aimed to investigate the effect of weight loss on breast cancer incidence. Method: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar. Databases were searched using subject headings, keyword searches and text word searches wherever possible using the search terms “Exercise” OR “weight loss” AND “breast cancer” OR “breast carcinoma” OR “breast neoplasm”. Inclusion criteria required a confirmed diagnosis of breast cancer, reporting of an odds ratio or data to calculate an odds ratio (and 95% confidence interval) and the use of an internal control group as the comparator. Exercise was catagorised as “high intensity” if it was vigorous exercise likely to cause sweating (ie. Running, competitive sport) while lower impact activities such as walking and golf were categorized as “low intensity”. The effect of the timing on breast cancer incidence was quantified across three time periods: adolescence, adulthood and post menopause. Collated data was assessed for heterogeneity and a pooled odds ratio calculated. Results: 111 studies were identified in the literature search of which 76 were included in the meta-analysis. Overall, both exercise and weight loss were associated with a significantly reduced risk of breast cancer in women (OR 0.77, 95% CI 0.72–0.81 and OR 0.74, 95% CI 0.60–0.93 respectively). Heterogeneity was high (I 2 =77.12) and publication bias was significant (p Conclusion: Breast cancer incidence is significantly reduced by both physical exercise and weight loss, especially in the postmenopausal population. Intensity, timing and nature of the exercise did not significantly alter the protective effect. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-11-01.

Correlation between thyroidal and peripheral blood total T cells, CD8+ T cells, and CD8+ T- regulatory cells and T-cell reactivity to calsequestrin and collagen XIII in patients with Graves’ ophthalmopathy

ABSTRACT Purpose/aim of the study: Graves’ ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves’ disease. Previous studies have suggested roles for thyroidal CD8+ T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO. Materials and methods: Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method. Results: We found a positive correlation between thyroidal CD8+ T cells and CD8+ T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves’ Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII. Conclusions: Our observations provide further evidence for a possible role of thyroidal CD8+ T cells, CD8+ T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.