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Purpose: To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non–small cell lung cancer (NSCLC). Experimental Design: Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell–specific defects, and clinicopathologic/survival associations of b2 microglobulin (b2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II b chain in >700 immunotherapy-na€ve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts. Results: Cancer cell–specific downregulation of HLA markers was identified in 30.4% of cases. b2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of b2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in

Essentials Cancer patients receiving anticoagulants for venous thromboembolism have an elevated bleeding risk. This secondary analysis of CATCH assessed characteristics of clinically relevant bleeding (CRB). CRB occurs in 15% of cancer patients with thrombosis using therapeutic doses of anticoagulation. After multivariate analysis, risk factors for CRB were age >75 years and intracranial malignancy. Summary Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg-1 once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of 75 years and intracranial malignancy.

Three hundred consecutive normal intravenous urograms were studied. The position of the ureter relative to the vertebral pedicles was assessed at different levels in patients from different racial groups. Medial placement of the ureter (where it overlay or was medial to a pedicle) was considerably commoner in black patients of African origin than in white Northern Europeans. In both races it occurred more frequently in males and in the young, and it was more common on the right side than on the left. The recognition of this normal variant, particularly in the black patient, is important in the interpretation of intravenous urograms.

The shape of the full bladder was studied during the course of 70 consecutive normal intravenous urograms. A conical or pear-shaped bladder was more frequently seen in patients of black African origin than in white Northern Europeans and more frequently in males than in females. This configuration was found in the absence of pelvic pathology and is considered a normal variant. Non-pathological medial deviation of the ureters is not closely associated, suggesting that the mechanisms for medial placement of the ureters and conical bladder are not necessarily interrelated.