Different Chemotherapy Regimens in the Management of Advanced or Metastatic Urothelial Cancer: a Bayesian Network Meta-Analysis of Randomized Controlled Trials

Background/Aims: Urothelial cancer (UC) as a chemotherapy-sensitive tumor, has achieved remarkable progresses in therapeutic paradigm, particularly in the advanced/metastatic stages. However, both clinicians and patients are confused when it comes to choosing the optimal chemotherapy. Hence, this article was aimed to conduct a comprehensive comparison of different chemotherapy regimens for advanced or metastatic UC in terms of survival benefits or adverse events. Methods: The online databases PubMed, EMBASE and Web of Science were searched systematically and comprehensively for randomized controlled trials (RCTs) up to September 15, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% credible interval (CrI) were calculated by Markov chain Monte Carlo methods. The effectiveness and safety of included regimens were conducted to provide a hierarchy by means of rank probabilities with the help of “R-3.4.0” software and the “gemtc-0.8.2” package. The surface under the cumulative ranking curve (SUCRA) was also incorporated in our analysis for ranking the corresponding chemotherapy regimens. Results: Ten different chemotherapy regimens involved in this article were predominantly of trials in a first-line setting, and eight clinical outcomes were ultimately analyzed in this study. In terms of Overall response rate (ORR), Overall survival (OS) or Progression-free survival (PFS)/Time to progression (TTP), the rank probabilities and SUCRA indicated that Paclitaxel/cisplatin/gemcitabine (PCG) was superior to gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), the traditional first-line treatment for advanced/metastatic UC. In the case of ORR or PFS/TTP, GC+sorafenib also displayed its superiority in comparison with GC or MVAC. Despite their survival benefits, PCG or GC+sorafenib presented a relatively higher incidence of adverse events. Conclusion: Our results revealed that by adding a paclitaxel or sorafenib into the first-line GC, it could yield a better survival benefit, but also worsen adverse events for advanced/ metastatic UC. Clinically, physicians should weigh the merits of these approaches to maximize the survival benefits of eligible patients

The risks of cancer development in systemic lupus erythematosus (SLE) patients: a systematic review and meta-analysis

Abstract Background Although accumulating data have suggested the development of cancer in systemic lupus erythematosus (SLE) patients, these results remain inconsistent. To examine such a putative association, this analysis reports the association between SLE and the risks of 24 cancer types. Methods Online databases PubMed, EMBASE, and Web of Science were searched comprehensively for eligible studies, published up to 15 May 2018. Pooled standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were utilized to reveal their associations. Results A total of 24 eligible studies were ultimately enrolled. Our results indicated that SLE was associated with increased risk of overall cancers, cancer risk in both genders, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, leukemia, multiple myeloma, cervix, vagina/vulva, renal, bladder, esophagus, gastric, hepatobiliary, lung, oropharynx, larynx, non-melanoma skin, and thyroid cancers. Additionally, SLE could reduce the risk of prostate cancer and cutaneous melanoma; however, it was not significantly associated with breast, uterus, ovarian, pancreatic, colorectal, or brain cancers. Conclusions Our results shed light SLE being correlated with increased risk for 16 involved cancers and decreased risk for prostate cancer and cutaneous melanoma. This comprehensive meta-analysis provides epidemiological evidence supporting the associations between SLE and cancer risk. This evidence could be utilized to drive public policies and to help guide personalized medicine to better manage SLE and reduce associated cancer morbidity and mortality

Extraperitoneal laparoscopic resection for retroperitoneal lymphatic cysts: initial experience

Abstract Background To assess the safety and efficacy of laparoscopic retroperitoneal resection for retroperitoneal lymphatic cysts. Methods A retrospective analysis was conducted based on clinical data from eight patients with hydronephrosis caused by retroperitoneal lymphatic cysts. All patients underwent laparoscopic retroperitoneal lymphatic cyst resection and received postoperative follow-up. A follow-up ultrasound was performed postoperatively every 6–12 months to evaluate the recovery of the hydronephrosis. Results All operations were successful, and their postoperative pathological results revealed lymphatic cyst walls. The operation time ranged from 43 to 88 min (mean: 62 min), with a blood loss of 20 to 130 mL (mean: 76 mL), and the length of hospital stay was 3 to 6 days (mean: 4.5 days). Within the follow-up of 12 to 36 months (mean: 28.5 months), great relief was detected in all eight cases, and no recurrence was found. Moreover, complications such as renal pedicle or renal pelvis injury were not observed. Conclusions Laparoscopic retroperitoneal lymphatic cyst resection is an effective treatment for retroperitoneal lymphatic cysts and has the advantages of being minimally invasive, producing less intraoperative blood loss and leading to a quick recovery. This treatment thus deserves further studies

Leveraging diverse cell-death patterns to predict the prognosis, immunotherapy and drug sensitivity of clear cell renal cell carcinoma

Abstract Clear cell renal cell carcinoma (ccRCC) poses clinical challenges due to its varied prognosis, tumor microenvironment attributes, and responses to immunotherapy. We established a novel Programmed Cell Death-related Signature (PRS) for ccRCC assessment, derived through the Least Absolute Shrinkage and Selection Operator (LASSO) regression method. We validated PRS using the E-MTAB-1980 dataset and created PCD-related clusters via non-negative matrix factorization (NMF). Our investigation included an in-depth analysis of immune infiltration scores using various algorithms. Additionally, we integrated data from the Cancer Immunome Atlas (TCIA) for ccRCC immunotherapy insights and leveraged the Genomics of Drug Sensitivity in Cancer (GDSC) database to assess drug sensitivity models. We complemented our findings with single-cell sequencing data and employed the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and qRT-PCR to compare gene expression profiles between cancerous and paracancerous tissues. PRS serves as a valuable tool for prognostication, immune characterization, tumor mutation burden estimation, immunotherapy response prediction, and drug sensitivity assessment in ccRCC. We identify five genes with significant roles in cancer promotion and three genes with cancer-suppressive properties, further validated by qRT-PCR and CPTAC analyses, showcasing gene expression differences in ccRCC tissues. Our study introduces an innovative PCD model that amalgamates diverse cell death patterns to provide accurate predictions for clinical outcomes, mutational profiles, and immune characteristics in ccRCC. Our findings hold promise for advancing personalized treatment strategies in ccRCC patients

Prognostic Significance of P16INK4a Expression in Penile Squamous Cell Carcinoma: A Meta-Analysis with Trial Sequential Analysis

Background. Recently, P16INK4a expression has been shown to be correlated with cancer-specific survival (CSS) in penile squamous cell carcinoma (SCC). Therefore, we performed this meta-analysis to clarify the prognostic value of P16INK4a for penile SCC. Methods. A systematic search was performed in PubMed, Embase, and Web of Science to identify all relevant articles up to May 25, 2017. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of included studies were pooled to estimate the prognostic value. Trial sequential analysis (TSA) was performed to assess the quantity and strength of survival evidence. Results. Five retrospective studies consisting of 323 cases were finally included. We found that P16INK4a positive expression was significantly associated with a better CSS of penile SCC (HR=0.45, 95%CI: 0.30-0.67, P<0.001). No heterogeneity or publication bias was noted among the included studies. Furthermore, TSA demonstrated that the findings were based on sufficient evidence. Conclusions. P16INK4a positive expression is independently associated with improved CSS for patients with penile SCC

Prognostic value of Lin28A and Lin28B in various human malignancies: a systematic review and meta-analysis

Abstract Background The mammalian homologs of Lin-28, Lin28 (also called Lin28A) and Lin28B, are promising cancer biomarkers. This meta-analysis was performed to evaluate the prognostic values of Lin28A and Lin28B in multiple human malignancies. Methods Systematic searches of the PubMed, Web of Science and Embase were used to identify relevant studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), or progression-free survival (PFS) were respectively calculated. Results 3772 Lin28A-associated patients and 1730 Lin28B-related cases were ultimately enrolled in this meta-analysis. The elevated expression level of Lin28A was significantly associated with poor OS (HR = 1.60, P < 0.001) and poor RFS/DFS/PFS (HR = 1.62, P < 0.001) in patients with malignancies. Lin28B overexpression significantly correlated with unfavorable OS (HR = 1.72, P < 0.001) and RFS/DFS/PFS (HR = 2.35, P < 0.001) of human malignancies. Conclusions Lin28A and Lin28B possess significant prognostic values in various human malignancies. Overexpression of Lin28A or Lin28B suggests poor prognosis for cancer patients

Prognostic role of galectin-3 expression in patients with solid tumors: a meta-analysis of 36 eligible studies

Abstract Background Galectin-3 as a β-galactoside-binding protein, has been found to be involved in tumor cell growth, anti-apoptosis, adhesion, angiogenesis, invasion, and distant metastases, indicating that it may play a pivotal role in cancer development and progression. However, their results remain debatable and inconclusive. Hence, this meta-analysis was performed to clarify the precise predictive value of galectin-3 in various cancers. Methods PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wanfang databases were searched comprehensively for eligible studies up to July 15, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated to demonstrate their associations. Results A total of 36 relevant studies were ultimately enrolled in this meta-analysis. Our results shed light on the significant association of elevated galectin-3 expression with reduced OS or DFS/RFS/PFS in overall cancer patients (pooled HR = 1.79, 95% CI 1.42–2.27, I 2= 67.3%, p < 0.01; pooled HR = 1.57, 95% CI 1.04–2.37, I 2= 67.1%, p = 0.001). In tumor type subgroup analysis, we found high expression of galectin-3 was correlated with shorter OS or DFS/RFS/PFS in colorectal cancer (pooled HR = 3.05, 95% CI 2.13–4.35, I 2= 0.0%, p = 0.734; pooled HR = 2.49, 95% CI 1.82–3.41, I 2 = 0.0%, p = 0.738; respectively) and meanwhile it merely associated with reduced OS in ovarian cancer or non-small cell lung cancer (pooled HR = 2.24, 95% CI 1.38–3.64, I 2= 0.0%, p = 0.910; pooled HR = 2.07, 95% CI 1.48–2.88, I 2= 0.0%, p = 0.563; separately). Conclusions Taken together, our results suggested that galectin-3 played an oncogenic role in colorectal cancer, ovarian cancer and non-small cell lung cancer, indicating it could be a promising biomarker and a novel therapeutic target for them. Further studies were warranted to validate our findings

Pre-treatment prognostic nutritional index may serve as a potential biomarker in urinary cancers: a systematic review and meta-analysis

Abstract Background To investigate the potential prognostic role of pre-treatment prognostic nutritional index (PNI) in urinary cancers. Methods Relevant articles were searched comprehensively from PubMed, Embase and Web of Science, up to November 2018. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to evaluate their associations. Result A total of 12 related articles including 6561 patients were ultimately enrolled. Our results indicated that a relatively lower level of pre-treatment PNI was associated with decreased OS, CSS/DSS and DFS/RFS/PFS (pooled HR = 1.68, 95% CI 1.45–1.95; pooled HR = 1.57, 95% CI 1.33–1.86; pooled HR = 1.75, 95% CI 1.53–1.99, respectively). Subsequent stratified analysis by cancer type for OS showed that PNI could also be a predictor no matter in renal cell cancer (RCC) or bladder cancer (BC) (pooled HR = 1.65, 95% CI 1.37–1.97 and pooled HR = 1.67, 95% CI 1.20–2.33). Similar results could be found in DFS/RFS/PFS (RCC: HR = 1.81, 95% CI 1.54–2.13 and BC: HR = 1.68, 95% CI 1.32–2.12) and in CSS/DSS (RCC: HR = 1.50, 95% CI 1.23–1.82 and upper tract urothelial carcinoma: HR = 1.61, 95% CI 1.13–2.28). As for the treatment subgroup, a relatively lower level of PNI could also be a positive predictor for OS (surgery: HR = 1.64, 95% CI 1.40–1.93; target therapy: HR = 1.88, 95% CI 1.34–2.63) and DFS/RFS/PFS (surgery: HR = 1.69, 95% CI 1.47–1.95; target therapy: HR = 2.14, 95% CI 1.50–3.05). Conclusion The outcomes of us shed light on that elevated pre-treatment PNI was positively associated with OS, CSS/DSS and DFS/RFS/PFS, indicating that it could be an independent prognostic factor in urinary cancers