Rawal, Bhupendra

The need for liver transplantation (LT) among older patients is increasing, but the role of LT in the elderly (≥70 years) is not well defined. We retrospectively reviewed all primary LTs from 1998 through 2016 at our center. Survival and associated risk factors were analyzed with Cox regression and Kaplan‐Meier methods for LT recipients in 3 age groups: <60, 60‐69, and ≥70 years. Among 2281 LT recipients, the median age was 56 years (range, 15‐80 years), and 162 were aged ≥70 years. The estimated 5‐ and 10‐year patient survival probabilities for elderly LT recipients were lower (70.8% and 43.6%) than for recipients aged 60‐69 years (77.2% and 64.6%) and <60 years (80.7% and 67.6%). Patient and graft survival rates associated with LT improved over time from the pre–Model for End‐Stage Liver Disease era to Share 15, pre–Share 35, and Share 35 for the cohort overall (P < 0.001), but rates remained relatively stable in septuagenarians throughout the study periods (all P > 0.45). There was no incremental negative effect of age at LT among elderly patients aged 70‐75 years (log‐rank P = 0.32). Among elderly LT recipients, greater requirement for packed red blood cells and longer warm ischemia times were significantly associated with decreased survival (P < 0.05). Survival of LT recipients, regardless of age, markedly surpassed that of patients who were denied LT, but it was persistently 20%‐30% lower than the expected survival of the general US population (P < 0.001). With the aging of the population, select older patients with end‐stage liver diseases can benefit from LT, which largely restores their expected life spans.

ObjectiveTo determine long‐term surgical outcomes of salvage autologous fascial sling placement after a failed synthetic midurethral sling.MethodsWomen who had undergone autologous fascial sling placement without concomitant pelvic surgery for a failed synthetic midurethral sling utilizing mesh with a minimum follow up of 36 months were identified. Charts were reviewed, and patients were contacted by telephone. Success was determined by the Patient Global Impression of Improvement. Secondary measures included the Incontinence Severity Index questionnaire, patient recommendation of the autologous fascial sling and need for further incontinence surgery.ResultsA total of 35 patients met the criteria, and 21 were successfully contacted. Of those contacted, the median age at surgery was 67 years (range 53–81 years) and at the time of the survey was 75 years (range 63–84 years) with median follow up of 74 months (range 36–127 years). Preoperatively, 12 patients (57.1%) had urethral hypermobility and 13 patients (61.9%) had mixed urinary incontinence. Eight patients (38.1%) had concomitant sling excision with five of those combined with urethrolysis at the time of the salvage operation. Patient Global Impression of Improvement success was noted in 16 patients (76.2%). A total of 11 patients (52.4%) were dry or had slight incontinence by the Incontinence Severity Index. One patient required additional anti‐incontinence surgery (4.8%). A total of 18 patients (85.7%) recommended the autologous fascial sling. No statistical impact was noted with sling excision (P = 0.62), mixed urinary incontinence (P = 0.61), age at surgery (P = 0.23), age at follow up (P = 0.15), length of follow up (P = 0.71) or first surgery type (transobturator tape vs retropubic; P = 1.00).ConclusionsAutologous fascial sling provides reasonable long‐term success as a salvage operation for failed midurethral slings.

Objective To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence ( BCR ) after salvage radiation therapy ( SRT ) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/ mL and rising as the definition of BCR . Patients and Methods We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks ( RR s) from multivariable Cox regression models. Results With a median follow‐up of 5.5 years after SRT , 354 patients (61%) experienced BCR . At 5 years after SRT , 40% of patients were free of BCR . Independent associations with BCR were identified for the PSA level before SRT ( RR [doubling]: 1.25, P < 0.001), pathological tumour stage ( RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score ( RR [7 vs <7] 1.63, P < 0.001; RR [8–10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status ( RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c ‐index of 0.66. Scores ranged from 0 to 7, and 5‐year freedom from BCR for different levels of the score was as follows: Score = 0–1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5–7: 15%. Conclusion We developed a scoring system that provides an estimation of the risk of BCR after SRT . These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting.

BACKGROUNDBiomarkers are routinely used to predict responses to systemic therapies, but their utility for predicting responses to local therapy for breast cancer is not known. This study determined whether biomarkers could predict responses to breast‐conserving therapy (BCT) and mastectomy.METHODSA review of the Surveillance, Epidemiology, and End Results database identified women diagnosed with early‐stage invasive ductal breast cancer and treated with BCT or mastectomy from 1998 to 2008. The estrogen receptor (ER) status and the histologic grade were used to construct 3 biomarker profiles: low risk (ER‐positive, low/intermediate grade), intermediate risk (ER‐positive, high grade), and high risk (ER‐negative, any grade). The primary measured outcome was disease‐specific survival (DSS).RESULTSBCT and mastectomy were performed in 114,486 patients (59.2%) and 79,035 patients (40.8%), respectively. There were 122,420 low‐risk patients (63.3%), 34,341 intermediate‐risk patients (17.7%), and 36,760 high‐risk patients (19.0%). Multivariate analyses were performed separately for patients with low‐, intermediate‐, and high‐risk tumors. The adjusted hazard ratios for DSS for patients who underwent mastectomy versus BCT for low‐, intermediate‐, and high‐risk tumors were 1.66 (95% confidence interval [CI], 1.54‐1.79; P < .001), 1.40 (95% CI, 1.29‐1.53; P < .001), and 1.27 (95% CI, 1.19‐1.35; P < .001), respectively.CONCLUSIONSPatients with ER‐positive, low‐grade breast cancers who underwent mastectomy had a 66% increase in disease‐specific mortality versus those who underwent BCT. Biomarker profiles defined by the ER status and grade may improve the selection of local therapy for breast cancer. Cancer 2015;121:2705‐2712. © 2015 American Cancer Society

Abstract Cigarette smoking is a major risk factor in the development of non–small cell lung cancer (NSCLC), which accounts for 80% of all lung cancers. Nicotine, the major addictive component of tobacco smoke, can induce proliferation, invasion, and epithelial-to-mesenchymal transition (EMT) in NSCLC cell lines and promote metastasis of NSCLC in mice. Here, we demonstrate that the scaffolding protein β-arrestin-1 is necessary for nicotine-mediated induction of mesenchymal genes vimentin and fibronectin as well as EMT regulators ZEB1 and ZEB2. Nicotine induced changes in cell morphology and ablate tight junctions consistent with EMT; β-arrestin-1, but not β-arrestin-2, was required for these changes. β-Arrestin-1 promoted the expression of the mesenchymal genes, as well as ZEB1 and ZEB2, through the mediation of the E2F1 transcription factor; this required Src kinase activity. Stimulation of multiple NSCLC cell lines with nicotine led to enhanced recruitment of β-arrestin-1 and E2F1 on vimentin, fibronectin, and ZEB1 and ZEB2 promoters. Furthermore, there was significantly more β-arrestin-1 and E2F1 associated with these promoters in human NSCLC tumors, and β-arrestin-1 levels correlated with vimentin and fibronectin levels in human NSCLC samples. A549-luciferase cells lacking β-arrestin-1 showed a significantly reduced capacity for tumor growth and metastasis when orthotopically implanted into the lungs of SCID-beige mice. Taken together, these studies reveal a novel role for β-arrestin-1 in the growth and metastasis of NSCLC. Cancer Res; 75(6); 1009–20. ©2015 AACR.