Citations

Background: Two-staged implant-based reconstruction (IBR) is the most common breast reconstructive modality. Recently, technological and surgical advances have encouraged surgeons to revisit prepectoral IBR. Data comparing prepectoral against subpectoral IBR in women under the age of 40 are lacking. Methods: Retrospective chart review of patients under the age of 40 years old, who underwent immediate 2-staged IBR at our institution, was performed. Patient’s demographics, clinical characteristics, operative details, and early surgical outcomes of prepectoral and subpectoral reconstruction were compared. Data with values of P < 0.05 were considered statistically significant. Results: Between 2012 and 2016, 100 patients (187 breasts) who underwent prepectoral and 69 patients (124 breasts) who underwent subpectoral IBR were included. Median follow-up was 17.9 and 17.5 months in the prepectoral and subpectoral groups, respectively. Total number of complications including both stages of reconstruction was 20 (10.7%) and 19 (15.3%) in the prepectoral and subpectoral groups, respectively (P = 0.227). Specific complications, including hematoma, seroma, skin flap necrosis, wound dehiscence, and breast infections, were not significantly different among groups. Ten (5.4%) devices, including implants and tissue expander, required explantation in the prepectoral group and 8 (6.5%) in the subpectoral group (P = 0.683). Explantation was most commonly due to infection (n = 14), and all of them occurred during the first stage (P < 0.001). Conclusions: Early complications and implant explantation rates are comparable among prepectoral and subpectoral breast reconstruction in women under 40 years old. Based on these results, we believe that prepectoral IBR is a safe, reliable, and promising reconstructive option.

Objective: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). Background: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. Methods: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. Results: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil–lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). Conclusions: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.

Background Preoperative planning software has been developed to measure glenoid version, glenoid inclination, and humeral head subluxation on computed tomography (CT) for shoulder arthroplasty. However, most studies analyzing the effect of glenoid positioning on outcome were done prior to the introduction of planning software. Thus, measurements obtained from the software can only be extrapolated to predict failure provided they are similar to classic measurements. The purpose of this study was to compare measurements obtained using classic manual measuring techniques and measurements generated from automated image analysis software. Methods Ninety-five two-dimensional computed tomography scans of shoulders with primary glenohumeral osteoarthritis were measured for version according to Friedman method, inclination according to Maurer method, and subluxation according to Walch method. DICOM files were loaded into an image analysis software (Blueprint, Wright Medical) and the output was compared with values obtained manually using a paired sample t-test. Results Average manual measurements included 13.8° version, 13.2° inclination, and 56.2% subluxation. Average image analysis software values included 17.4° version (3.5° difference, p < 0.0001), 9.2° inclination (3.9° difference, p < 0.001), and 74.2% for subluxation (18% difference, p < 0.0001). Conclusions Glenoid version and inclination values from the software and manual measurement on two-dimensional computed tomography were relatively similar, within approximately 4°. However, subluxation measurements differed by approximately 20%.

Abstract Oncolytic viruses hold promise as “self-amplifying” cancer therapies wherein a virally killed cell can produce thousands of new viral “drugs” that can kill more cancer cells. Oncolytic viruses may also serve to reawaken or initiate immune responses against cancers by virtue of their abilities to lyse cells, liberate cancer antigens, and provide viral DNA and proteins as immune adjuvants. Oncolytics can also be armed with cytokine or checkpoint inhibitors to amplify antitumor immune responses. Adenoviruses (Ads) are one family of oncolytic viruses. Most human studies have used human Ad serotype 5 (Ad5). Unfortunately, most patients are already immune to Ad5, increasing the likelihood that the agent will be neutralized if used as a cancer therapy. In this work, low seroprevalence Ad6 and Ad57 oncolytic viruses were tested as intravenous therapies against distant prostate cancer sites. After prostate cell infection in vitro, Ad viruses executed these cells efficiently and generated 10,000 to 100,000 progeny infectious viruses. This genome replication also amplified transgene protein production by 100 to 1,000-fold when compared to nonreplicating Ad vectors. Ad5, Ad6, and Ad57 were injected intravenously a single time in nude mice bearing human prostate tumors, and toxicity and efficacy were assessed. Ad6 and 57 produced 30-fold lower liver damage and less toxicity than Ad5. Ad6 and Ad57 significantly repressed the growth of androgen-resistant human DU145 prostate tumors and androgen-sensitive LNCaP prostate tumors and extended survival after single intravenous injection in mice. Ad6 and Ad57 E1 protein were also modified to protect normal cells from viral oncolysis while allowing the virus to amplify and kill prostate cancer cells having perturbations in p300 and pRB pathways. These and other data suggest that targeted and untargeted low seroprevalent Ad6 and Ad57 have better efficacy and safety than the benchmark oncolytic virus Ad5 for systemic therapy of advanced prostate cancer. Citation Format: Tien Nguyen, Michael A. Barry. Systemic oncolytic virotherapy for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A062.

OBJECTIVES: Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials and examined the relationship between histologic and endoscopic outcomes. METHODS: MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for randomized controlled trials of aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial–normal random-effect or fixed-effect models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel–Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission. RESULTS: Seventy-four studies (68 induction and 7 maintenance) were identified. Topical aminosalicylate enemas [37.2%, 95% confidence interval (CI), 29.0–46.3] and suppositories (44.9%, 95% CI, 28.9–62.3) had the highest induction of histologic remission rates. Aminosalicylate enemas (RR = 4.14, 95% CI, 2.35–7.31), aminosalicylate suppositories (RR = 3.94, 95% CI, 1.26–12.32), and budesonide multimatrix (RR = 1.47, 95% CI 1.08–1.99) had higher histologic remission rates than placebo. Data were lacking for biologics and immunosuppressives. The pooled histologic remission rate for placebo in induction studies was 10.4% (95% CI, 7.1–15.2). Histologic and endoscopic remission correlated strongly ( r = 0.66; 95% CI, 0.50–0.78). In multivariate analysis of placebo-arm data, less severe clinical disease activity and corticosteroid use were associated with higher histologic remission rates. Similarly, mild clinical disease activity was associated with higher histologic remission rates when active-arm data were analyzed. CONCLUSIONS: Histologic remission rates for current UC treatments ranged from 15.0% to 44.9% according to drug class and patient population with the highest rates observed for topical aminosalicylates. Placebo remission rates were low with relatively narrow CIs. These data provide benchmarks to inform future trial design. Histologic remission is a potential treatment target in clinical practice.