The Application of Fat-Free Mass Index for Survival Prediction in Cancer Patients With Normal and High Body Mass Index.

Background: Fat-free mass (FFM) depletion can be masked by a stable body weight or weight gain in the presence of a normal or high body mass index (BMI). This study investigated the prognostic value of low fat-free mass index (FFMI) in cancer patients with normal or high BMI. Methods: This multicenter retrospective cohort study included 1,602 cancer patients with normal/high BMI. The association of FFMI with patients' overall survival (OS) was analyzed by the Kaplan-Meier method and a Cox model. Results: In this analysis, there were 974 (60.8%) females and 628 (39.2%) males. Low FFMI was associated with worse OS when compared with those patients with normal FFMI. After multivariate adjustment, low FFMI was demonstrated to be an independent unfavorable prognostic factor (HR: 1.69; 95% CI: 1.28, 2.23; P < 0.001) in cancer patients with normal/high BMI. For specific tumor type, low FFMI was found to be associated with worse prognosis in patients with lung cancer, breast cancer and upper gastrointestinal cancer. In subgroup analysis, the association of low FFMI with worse survival was significantly modified by weight loss (P for interaction = 0.012), and those patients with concurrent low FFMI and weight loss showed the worst prognosis (HR: 3.53; 95% CI: 2.04, 6.11; P < 0.001). Conclusion: Low FFMI was associated with worse prognosis in cancer patients with normal/high BMI. This study highlights the usefulness of FFMI for prognostic estimation in these patients.

Incidental para-ureteral aggressive angiomyxoma: a rare case report and literature review.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. CONCLUSIONS: We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

Incidence and risk of proteinuria associated with newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: an up-to-date meta-analysis of randomized controlled trials.

Objective: We performed a meta-analysis to quantify the overall incidence and risk of proteinuria associated with five newly approved VEGFR-TKIs (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) in cancer patients.Methods: Pubmed, Embase, ASCO abstracts, and ESMO abstracts were searched to identify relevant studies. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were estimated using random or fixed effects models according to the heterogeneity of included studies.Results: A total of 9,446 patients from 20 RCTs were included for the meta-analysis. The use of newly approved VEGFR-TKIs was associated with an increased risk of all-grade (RR 2.35, 95% CI 1.69-3.27, P < 0.001) and high-grade (RR 3.70, 95% CI 2.09-6.54, P < 0.001) proteinuria. On subgroup analysis, lenvatinib, axitinib, and vandetanib significantly increased the risk of all-grade proteinuria, and lenvatinib was associated with an increased risk of high-grade proteinuria. In addition, the risk of developing high-grade proteinuria events was significant for patients with hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), but not for patients with colorectal cancer (CRC) and thyroid cancer (TC).Conclusion: Treatment with newly approved VEGFR-TKIs significantly increases the risk of developing proteinuria events in cancer patients, especially for patients treated with lenvatinib.

Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: a meta-analysis of randomized controlled trials.

PURPOSE: Hematologic toxicities, including neutropenia, thrombocytopenia, and anemia, are major adverse effects of PARP inhibitors (PARPis), but the incidence rate and overall risk has not been systematically studied. Therefore, we conducted a meta-analysis of published clinical trials to investigate the incidence and relative risks (RRs) of severe (high-grade) hematologic events in cancer patients treated with PARPis. METHODS: PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were Phase II and III randomized controlled trials (RCTs) of PARPis in cancer patients with adequate safety data on hematologic toxicities. The summary incidence, RRs, and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 2,479 patients from 12 RCTs revealed that the incidence of PARPi-associated severe hematologic toxicities was, respectively: neutropenia: 32.9% (95% CI, 20.5%-48.3%); thrombocytopenia: 15.9% (95% CI, 9.5%-25.4%), and anemia: 9.1% (95% CI, 5.1%-15.7%). Olaparib was associated with an increased risk of severe neutropenia. Veliparib was associated with an increased risk of severe neutropenia and thrombocytopenia. Niraparib was associated with an increased risk of severe thrombocytopenia, anemia, and neutropenia. When stratified by combination therapy, significantly increased risk of hematologic toxicities was observed for patients treated with PARPis monotherapy and PARPis combined with single-agent chemotherapy. CONCLUSION: Treatment with PARPis olaparib, veliparib, and niraparib is associated with a significant increase in the risk of hematologic toxicities in cancer patients, and frequent clinical monitoring should be emphasized when managing these PARPis.

Genomic expression profiling and bioinformatics analysis of pancreatic cancer.

Pancreatic cancer is a polygenic disease and the fourth leading cause of cancer-associated mortality worldwide; however, the tumorigenesis of pancreatic cancer remains poorly understood. Research at a molecular level, which includes the exploration of biomarkers for early diagnosis and specific targets for therapy, may effectively aid in the diagnosis of pancreatic cancer in its early stages and in the development of targeted molecular­biological approaches for treatment, thus improving prognosis. By conducting expression profiling in para­carcinoma, carcinoma and relapse of human pancreatic tissues, 319 genes or transcripts with differential expression levels >3­fold between these tissue types were identified. Further analysis with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that the translation, nucleus assembly processes and molecular functions associated with vitamin B6 and pyridoxal phosphate binding in pancreatic carcinoma were abnormal. Pancreatic cancer was additionally identified to be closely associated with certain autoimmune diseases, including type I diabetes mellitus and systemic lupus erythematosus.

Prognostic significance of neutrophil lymphocyte ratio in patients with gastric cancer: a meta-analysis.

BACKGROUND: Several studies have shown that neutrophil lymphocyte ratio (NLR) may be associated with the prognosis of gastric cancer (GC), but the results are controversial. METHODS: This study was performed to evaluate the prognostic implications of neutrophil lymphocyte ratio of GC in all available studies. We surveyed 2 medical databases, PubMed and EMBASE, to identify all relevant studies. Data were collected from studies comparing overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) in patients with GC. RESULTS: Ten studies (n = 2,952) evaluated the role of NLR as a predictor of outcome were involved for this meta-analysis (10 for OS, 3 for DFS, and 2 for PFS). Overall and disease-free survival were significantly better in patients with low NLR value and the pooled HRs was significant at 1.83 ([95% CI], 1.62-2.07) and 1.58 ([95% CI], 1.12-2.21), respectively. For progression-free survival, the pooled hazard ratio of NLR was significant at 1.54 ([95% CI], 1.22-1.95). No evidence of significant heterogeneity or publication bias for OS and DFS was seen in any of the included studies. CONCLUSION: This meta-analysis indicated that elevated NLR may be associated with a worse prognosis for patients with GC.

Hypoxia inducible factor-1α suppresses Peroxiredoxin 3 expression to promote proliferation of CCRCC cells.

Peroxiredoxin 3 (Prx3) is a mitochondrial member of the antioxidant family of thioredoxin peroxidases that uses mitochondrial thioredoxin 2 as a source of reducing equivalents to scavenge hydrogen peroxide (H2O2). Here, we report that the protein levels of Prx3 are significantly reduced in VHL-deficient clear cell renal cell carcinoma (CCRCC). Furthermore, stabilization of HIF-1α protein, caused either by VHL deficiency under normoxia, or by hypoxia, significantly reduced Prx3 expression. Luciferase-reporter and chromatin-immunoprecipitation assays indicated that HIF-1α binds to the hypoxia-responsive elements of PRDX3 promoter and represses its transcription. Finally, shRNA-based assays suggested that Prx3 downregulation is required for the HIF-1α-dependent proliferation of CCRCC cells. Taken together, our results shed new light onto the mechanism of HIF-1α-dependent proliferation in CCRCC cells.