Citations

Abstract Background: Hepatocellular carcinoma (HCC) is a lethal malignancy that currently ranks fourth in cancer-related deaths in the US and is projected to become the third leading cause of cancer death in the US by 2030. Thus, there is a pressing need to identify modifying risk factors to improve survival after diagnosis of HCC. Statins and metformin are among the most commonly prescribed medications in the elderly in the US and there are experimental data suggesting that these medications may improve overall survival after cancer diagnosis; however, results from observational studies have been equivocal. We therefore investigated the potential benefits of pre- and post-diagnosis use of statins and metformin both independently and jointly on overall survival after diagnosis of HCC. Methods: The study was performed using data from the Surveillance, Epidemiology, and End Results (SEER-18) registry linked to Medicare claims data and included 8,922 elderly (≥65 years) patients diagnosed with HCC between 2009-2013. Data on metformin and statins use were extracted from the Medicare Part D Claims file and the patients were grouped as statins only users, metformin only users, both statins and metformin users, or neither (i.e., non-users, referent group). We assessed association of both pre-diagnosis (≥2 years) and post-diagnosis statins and metformin use on risk of death after diagnosis of HCC. Statins users were further categorized into high potency statins users (simvastatin, atorvastatin, and rosuvastatin) or low potency statins users (pravastatin, lovastatin, and fluvastatin) and compared with non-users. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for multiple risk factors, including age sex, race, cancer stage at diagnosis, cancer grade, first course therapy, neighborhood level education and income, Charlson comorbidity index, and diabetes severity index. Results: Compared with non-users, post-diagnosis statins use was independently associated with 27% lower risk of death after diagnosis of HCC (HR=0.73, 95% CI: 0.60-0.88; p-value = 0.002), adjusting for pre-diagnosis statins use and other risk factors. Further analysis showed that the association for post-diagnosis statins use is evident only among high potency statins users (HR=0.72, 95% CI: 0.60-0.88; users versus non-users) but not low potency statins users (HR=0.83, 95% CI: 0.55-1.25; users versus non-users). No association was found for pre-diagnosis statins use or for pre- or post-diagnosis metformin use. Conclusions: This study suggests that post-diagnosis statins use, particularly high potency statins use, may improve overall survival after diagnosis of HCC. Metformin use, both before and after diagnosis of HCC, is not associated with overall survival. Citation Format: Samuel O. Antwi, Zhuo Li, Kabir Mody, Tushar C. Patel. Independent and joint use of statins and metformin on overall survival after diagnosis of hepatocellular carcinoma: A SEER-Medicare matched study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1192.

Background and ObjectivesSurgical resection of retroperitoneal sarcomas (RPS) often involves removal of the ipsilateral kidney. We evaluated the long‐term post‐operative renal function in patients who underwent a nephrectomy as part of their en‐bloc resection of RPS.MethodsRetrospective review of an institutional database identified RPS patients who underwent nephrectomy for curative intent from 1990 to 2014. The primary outcome measured was chronic kidney disease (CKD) calculated by the glomerular filtration rate (GFR).ResultsOf the 47 patients in our study, 19 (40%), 18 (38%), and 10 (21%) patients had a preoperative CKD stage 1, 2, and 3, respectively. The GFR decreased by an average of 33.4 mL/min/1.73 m2 with 66% of patients demonstrating mild progression of their renal impairment. Only three (6%) patients progressed to CKD stage 4 or 5, one of which required life‐long dialysis.ConclusionNephrectomy as part of an en‐bloc resection is associated with a decrease in GFR that is not clinically significant. Fear of kidney failure should not prevent a surgeon from performing a nephrectomy in the treatment of RPS.

Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian‐predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. HCC cases were recruited in a comprehensive cancer center while the matched controls were recruited from family practice units from the same catchment area. For risk analyses, unconditional logistic regression analyses were performed in HCC patients and matched healthy controls. Overall survival analyses were performed using Cox proportional hazard models, Kaplan‐Meier curves, and log‐rank tests. In 266 HCC cases and 536 controls, no association between either BRM promoter polymorphism (BRM‐741 or BRM‐1321) and risk of HCC was identified (P > 0.10 for all comparisons). There was significant worsening of overall survival as the number of variant alleles increased: BRM‐741 per variant allele adjusted hazards ratio (aHR) 5.77, 95% confidence interval (CI) 2.89‐11.54 and BRM‐1321 per variant allele aHR 4.09, 95%CI 2.22‐7.51. The effects of these two polymorphisms were at least additive, where individuals who were double homozygotes for the variant alleles had a 45‐fold increase in risk of death when compared to those who were double wild‐type for the two polymorphisms. Two BRM promoter polymorphisms were strongly associated with HCC prognosis but were not associated with increased HCC susceptibility. The association was strongest in double homozygotes for the allele variants.

Renal function improves early after left ventricular assist device (LVAD) implantation but later decline has been observed. We sought to determine the occurrence and evaluate possible causes for this decline. In 62 consecutive patients with HeartMateII LVAD with available calculated glomerular filtration rate (GFR, ml/min/1.73 m2) 1 year after implant, GFR was assessed repeatedly and possible predictors for decline from 3 to 12 months were investigated. Post-mortem renal specimens for patients supported with an LVAD were evaluated. GFR 54.5 ± 19.5 at admission increased to 66.4 ± 22.3 preoperatively and to 79.2 ± 30.1 ~1 month after implantation. Subsequently at ~3 months GFR declined to 74.7 ± 25.4, at ~6 months to 68.8 ± 23.1, and ~1 year after implant to 63.9 ± 17.7. Glomerular filtration rate at 1 year was significantly lower (p < 0.0001, p < 0.0001, p = 0.005) than GFR 1, 3, and 6 months after implant. Early rise in GFR after surgery was not associated with late decline. Shorter bypass time (β = −0.09, p = 0.048) and higher albumin 3 months after LVAD (β = 14.4, p = 0.025) were significantly associated with less later decline in GFR. Arteriosclerosis was identified in autopsy renal specimens. In conclusion, early gains in renal function after LVAD implant are not sustained in many patients. Patient, device, and operative factors may influence long-term renal function in these patients.