Raising a Small Flock of Sheep in Ohio

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Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Open versus laparoscopic simultaneous bilateral adrenalectomy

To compare our experience with synchronous bilateral adrenalectomy using laparoscopic and open techniques. Laparoscopic adrenalectomy has become the reference standard for management of benign unilateral adrenal pathologic findings. This was a nonrandomized retrospective chart review of 12 known patients who underwent simultaneous bilateral adrenalectomy, comparing five laparoscopic and seven open procedures. One urologic surgeon performed all laparoscopic cases, and one general surgeon performed all open procedures. All patients had Cushing’s disease or syndrome. The average patient age was 47.4 years (range 24 to 71) and 42.4 years (range 19 to 70), with an average body mass index of 38.2 kg/m 2 and 36.0 kg/m 2 for the laparoscopic and open groups, respectively. The operating time was on average 60 minutes longer for the laparoscopic group. No open conversions were necessary. The median blood loss (100 versus 500 mL, P <0.01) and hematocrit drop (8.5% versus 12.6%, P = 0.05) were lower for the laparoscopic group. The transfusion rates and hospital stay trended lower in the laparoscopic group (20% versus 57% and 3 versus 8.5 days, respectively). Specimen weights for both the right and left glands trended larger for the laparoscopic group. The complication rates were similar between groups at 60% for the laparoscopic versus 71% for the open groups. Simultaneous laparoscopic bilateral adrenalectomy is safe and effective. Compared with the open approach, it resulted in decreased blood loss, lower transfusion rate, and a trend toward a shorter hospital stay, although the operating time was longer. The laparoscopic approach should be the treatment of choice for bilateral adrenalectomy

Keeping a Small Beef Cow Herd in Ohio

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Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell–activating factor (BAFF) levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF/B-cell ratios compared with patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre–germinal center (GC) B cells and post-GC “plasmablast-like” cells, suggesting in vivo BAFF dependence of these 2 CD27+ B-cell subsets. Circulating CD27+ B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27+ B cells in the first year after HSCT. These studies delineate specific abnormalities of B-cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC