Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR

Quantification of B2 glenoid morphology in total shoulder arthroplasty

BACKGROUND: B2 glenoid morphology is challenging to address with shoulder reconstruction. Deformity often renders current techniques inadequate, necessitating compromises that limit long-term implant durability. The purpose of this study was to perform in vivo measurements of glenoid deformity to better appreciate the orientation of the B2 biconcavity demarcation and erosion that surgeons face intraoperatively. MATERIALS AND METHODS: A consecutive 106 total shoulder arthroplasty cases for primary glenohumeral osteoarthritis were studied. We classified glenoids by direct visualization and noted lines of biconcavity demarcation and erosion in B2s. We then calculated the angle of erosion as that between the back side of the unsupported, smooth-backed glenoid sizer disk and the neoglenoid. We obtained depth measurements throughout the reaming process and monitored subchondral bone. RESULTS: We classified 43 of 106 glenoids (41%) as B2. A biconcavity demarcation line between the paleoglenoid and the neoglenoid was present, on average, from the 1-o\u27clock to the 7-o\u27clock position for a left shoulder. Mean depth of erosion was 4.4 mm, occurring at 114° on a Cartesian coordinate system for a left shoulder. The mean angle of erosion was 18° (range, 8°-43°). Despite reaming, 20 of 43 B2 glenoids (47%) had incompletely supported components at final seating. CONCLUSIONS: Arthritic B2 glenoids are common, and their maximal erosion is usually posteroinferior. Use of standard glenoid components to reconstruct them may require significant subchondral bone removal to achieve complete bone support. Alternatively, as a compromise, maintenance of subchondral bone in these cases requires implanting components with incomplete bony support

Shoulder Arthroplasties have Fewer Complications than Hip or Knee Arthroplasties in US Veterans

Total shoulder arthroplasties (TSA) are being performed more commonly for treatment of arthritis, although fewer than either hip (THA) or knee (TKA) arthroplasties. Total shoulder arthroplasty also provides general health improvements that are comparable to THA. One study suggests TSAs are associated with lower morbidity and mortality than THAs and TKAs. To confirm and extend that study, we therefore examined the association of patient characteristics (sociodemographics, comorbid illness, and other risk factors) with 30-day complications for patients undergoing TSAs, THAs, or TKAs. We used data from the Veterans Administration (VA) National Surgical Quality Improvement Program (NSQIP) for fiscal years 1999 to 2006. Sociodemographics, comorbidities, health behaviors, operative factors, and complications (mortality, return to the operating room, readmission within 14 days, cardiovascular events, and infections) were available for 10,407 THAs, 23,042 TKAs, and 793 TSAs. Sociodemographic features were comparable among groups. The mean operative time was greater for TSAs (3.0 hours) than for TKAs (2.2 hours) and THAs (2.4 hours). The 30-day mortality rates were 1.2%, 1.1%, and 0.4% for THAs, TKAs, and TSAs, respectively. The corresponding postoperative complication rates were 7.6%, 6.8%, and 2.8%. Adjusting for multiple risk factors, complications, readmissions, and postoperative stays were less for TSAs versus THAs and TKAs. In a VA population, TSAs required more operative time but resulted in shorter stays, fewer complications, and fewer readmissions than THAs and TKAs

One and two-year clinical outcomes for a polyethylene glenoid with a fluted peg: one thousand two hundred seventy individual patients from eleven centers

PURPOSE: Clinical shoulder science lacks a benchmark against which the early clinical value of new glenoid components can be compared; such a benchmark may be derived from a multicenter study of patients receiving an established, internationally used design of glenoid component. METHODS: We obtained data from 11 centers on 1270 patients having total shoulder arthroplasty using an all-polyethylene component with a fluted central peg. We analyzed individual patient outcomes at 1 and 2 years after surgery. We compared the improvement for each patient to the minimal clinically important difference (MCID) and calculated each patient\u27s improvement as a percent of maximal possible improvement (MPI). RESULTS: The preoperative scores improved from SST 3 ± 2, ASES 37 ± 15, Constant score 36 ± 16, and Penn score 30 ± 19 to SST 10 ± 2, ASES 90 ± 12, Constant 76 ± 13, and Penn 80 ± 24 (p \u3c 0.001 for each). A high percentage of patients improved by more than the MCID (SST 96%, ASES 98%, Constant 94%, Penn 93%) and obtained improvement of at least 30% of the MPI (SST 95%, ASES 98%, Constant 91%, Penn 87%). The clinical outcomes realized with this glenoid design were not worse for the 41% of shoulders with preoperative type B glenoids or for the 30% of shoulders with more than 15 degrees of glenoid retroversion. CONCLUSIONS: Individual patients from 11 international practices having total shoulder arthroplasty using a basic glenoid component design obtained highly significant clinical outcomes, providing a benchmark against which the early outcomes of new designs can be compared to determine whether they provide increased clinical value

One and two-year clinical outcomes for a polyethylene glenoid with a fluted peg : one thousand two hundred seventy individual patients from eleven centers

Purpose: Clinical shoulder science lacks a benchmark against which the early clinical value of new glenoid components can be compared; such a benchmark may be derived from a multicenter study of patients receiving an established, internationally used design of glenoid component. Methods: We obtained data from 11 centers on 1270 patients having total shoulder arthroplasty using an all-polyethylene component with a fluted central peg. We analyzed individual patient outcomes at 1 and 2years after surgery. We compared the improvement for each patient to the minimal clinically important difference (MCID) and calculated each patient's improvement as a percent of maximal possible improvement (MPI). Results: The preoperative scores improved from SST 32, ASES 37 +/- 15, Constant score 36 +/- 16, and Penn score 30 +/- 19 to SST 10 +/- 2, ASES 90 +/- 12, Constant 76 +/- 13, and Penn 80 +/- 24 (p<0.001 for each). A high percentage of patients improved by more than the MCID (SST 96%, ASES 98%, Constant 94%, Penn 93%) and obtained improvement of at least 30% of the MPI (SST 95%, ASES 98%, Constant 91%, Penn 87%). The clinical outcomes realized with this glenoid design were not worse for the 41% of shoulders with preoperative type B glenoids or for the 30% of shoulders with more than 15 degrees of glenoid retroversion. Conclusions: Individual patients from 11 international practices having total shoulder arthroplasty using a basic glenoid component design obtained highly significant clinical outcomes, providing a benchmark against which the early outcomes of new designs can be compared to determine whether they provide increased clinical value