A HER2-targeted Antibody-Drug Conjugate, RC48-ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer.

More than half of non-muscle-invasive bladder cancer (NMIBC) patients eventually relapse even if treated with surgery and BCG without optional bladder-preserving therapy. This study aims to investigate the antitumor activity and safety of a HER2-targeted antibody-drug conjugate, RC48-ADC, intravesical instillation for NMIBC treatment. In this preclinical study, it is revealed that human epidermal growth factor receptor 2 (HER2) expression scores of 1+, 2+, and 3+ are recorded for 16.7%, 56.2%, and 14.6% of NMIBC cases. The antitumor effect of RC48-ADC is positively correlated with HER2 expression in bladder cancer (BCa) cell lines and organoid models. Furthermore, RC48-ADC is revealed to exert its antitumor effect by inducing G2/M arrest and caspase-dependent apoptosis. In an orthotopic BCa model, tumor growth is significantly inhibited by intravesical instillation of RC48-ADC versus disitamab, monomethyl auristatin E, epirubicin, or phosphate-buffered saline control. The potential toxicity of intravesical RC48-ADC is also assessed by dose escalation in normal nude mice and revealed that administration of RC48-ADC by intravesical instillation is safe within the range of effective therapeutic doses. Taken together, RC48-ADC demonstrates promising antitumor effects and safety with intravesical administration in multiple preclinical models. These findings provide a rational for clinical trials of intravesical RC48-ADC in NMIBC patients.

Construction of 3D and 2D contrast-enhanced CT radiomics for prediction of CGB3 expression level and clinical prognosis in bladder cancer.

Objective: The purpose of this study was to construct a 3D and 2D contrast-enhanced computed tomography (CECT) radiomics model to predict CGB3 levels and assess its prognostic abilities in bladder cancer (Bca) patients. Methods: Transcriptome data and CECT images of Bca patients were downloaded from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) database. Clinical data of 43 cases from TCGA and TCIA were used for radiomics model evaluation. The Volume of interest (VOI) (3D) and region of interest (ROI) (2D) radiomics features were extracted. For the construction of predicting radiomics models, least absolute shrinkage and selection operator regression were used, and the filtered radiomics features were fitted using the logistic regression algorithm (LR). The model's effectiveness was measured using 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC of ROC). Result: CGB3 was a differential expressed prognosis-related gene and involved in the immune response process of plasma cells and T cell gamma delta. The high levels of CGB3 are a risk element for overall survival (OS). The AUCs of VOI and ROI radiomics models in the training set were 0.841 and 0.776, while in the validation set were 0.815 and 0.754, respectively. The Delong test revealed that the AUCs of the two models were not statistically different, and both models had good predictive performance. Conclusion: The CGB3 expression level is an important prognosis factor for Bca patients. Both 3D and 2D CECT radiomics are effective in predicting CGB3 expression levels.

UBE2S interacting with TRIM21 mediates the K11-linked ubiquitination of LPP to promote the lymphatic metastasis of bladder cancer.

Lymphatic metastasis is the most common pattern of bladder cancer (BCa) metastasis and has an extremely poor prognosis. Emerging evidence shows that ubiquitination plays crucial roles in various processes of tumors, including tumorigenesis and progression. However, the molecular mechanisms underlying the roles of ubiquitination in the lymphatic metastasis of BCa are largely unknown. In the present study, through bioinformatics analysis and validation in tissue samples, we found that the ubiquitin-conjugating E2 enzyme UBE2S was positively correlated with the lymphatic metastasis status, high tumor stage, histological grade, and poor prognosis of BCa patients. Functional assays showed that UBE2S promoted BCa cell migration and invasion in vitro, as well as lymphatic metastasis in vivo. Mechanistically, UBE2S interacted with tripartite motif containing 21 (TRIM21) and jointly induced the ubiquitination of lipoma preferred partner (LPP) via K11-linked polyubiquitination but not K48- or K63-linked polyubiquitination. Moreover, LPP silencing rescued the anti-metastatic phenotypes and inhibited the epithelial-mesenchymal transition of BCa cells after UBE2S knockdown. Finally, targeting UBE2S with cephalomannine distinctly inhibited the progression of BCa in cell lines and human BCa-derived organoids in vitro, as well as in a lymphatic metastasis model in vivo, without significant toxicity. In conclusion, our study reveals that UBE2S, by interacting with TRIM21, degrades LPP through K11-linked ubiquitination to promote the lymphatic metastasis of BCa, suggesting that UBE2S represents a potent and promising therapeutic target for metastatic BCa.

Screening ANLN and ASPM as bladder urothelial carcinoma-related biomarkers based on weighted gene co-expression network analysis.

Introduction: Bladder cancer (BLCA) is one of the most common malignancies in the urinary system with a poor prognosis and high treatment costs. Identifying potential prognostic biomarkers is significant for exploring new therapeutic and predictive targets of BLCA. Methods: In this study, we screened differentially expressed genes using the GSE37815 dataset. We then performed a weighted gene co-expression network analysis (WGCNA) to identify the genes correlated with the histologic grade and T stage of BLCA using the GSE32548 dataset. Subsequently, Kaplan Meier survival analysis and Cox regression were used to further identify prognosis-related hub genes using the datasets GSE13507 and TCGA-BLCA. Moreover, we detected the expression of the hub genes in 35 paired samples, including BLCA and paracancerous tissue, from the Shantou Central Hospital by qRT-polymerase chain reaction. Results: This study showed that Anillin (ANLN) and Abnormal spindle-like microcephaly-associated gene (ASPM) were prognostic biomarkers for BLCA. High expression of ANLN and ASPM was associated with poor overall survival.The qRT-PCR results revealed that ANLN and ASPM genes were upregulated in BLCA, and there was a correlation between the expression of ANLN and ASPM in cancer tissues and paracancerous tissue. Additionally, the increasing multiples in the ANLN gene was obvious in high-grade BLCA. Discussion: In summary, this preliminary exploration indicated a correlation between ANLN and ASPM expression. These two genes, serving as the risk factors for BLCA progression, might be promising targets to improve the occurrence and progression of BLCA.

Predictive model for urosepsis in patients with Upper Urinary Tract Calculi based on ultrasonography and urinalysis using artificial intelligence learning

ABSTRACT Purpose To construct a predicting model for urosepsis risk for patients with upper urinary tract calculi based on ultrasound and urinalysis. Materials and Methods A retrospective study was conducted in patients with upper urinary tract calculi admitted between January 2016 and January 2020. The patients were randomly grouped into the training and validation sets. The training set was used to identify the urosepsis risk factors and construct a risk prediction model based on ultrasound and urinalysis. The validation set was used to test the performance of the artificial neural network (ANN). Results Ultimately, 1716 patients (10.8% cases and 89.2% control) were included. Eight variables were selected for the model: sex, age, body temperature, diabetes history, urine leukocytes, urine nitrite, urine glucose, and degree of hydronephrosis. The area under the receiver operating curve in the validation and training sets was 0.945 (95% CI: 0.903-0.988) and 0.992 (95% CI: 0.988-0.997), respectively. Sensitivity, specificity, and Yuden index of the validation set (training set) were 80.4% (85.9%), 98.2% (99.0%), and 0.786 (0.849), respectively. Conclusions A preliminary screening model for urosepsis based on ultrasound and urinalysis was constructed using ANN. The model could provide risk assessments for urosepsis in patients with upper urinary tract calculi.

Influencing factors for mortality in prostate cancer patients with T1 and T2 stage: a retrospective cohort study.

Background: Few reports have focused on the influencing factors of localized prostate cancer (PCa)-specific mortality so far. This study aimed to develop a competitive risk model for identifying the factors influencing the localized PCa mortality rate based on 135,310 subjects in the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We included 135,310 localized PCa male patients from SEER database 2004-2016 in this cohort study, and collected the baseline information of all patients, including age of diagnosis, race, marital status, socioeconomic status (SES), American Joint Committee on Cancer (AJCC) stage, prostate-specific antigen (PSA) Gleason score, and so on. The outcome was considered as PCa-specific mortality in this study. The end time of follow-up was November 2018. Independent risk factors were examined by multivariate Fine-Gray analysis. The results are shown by hazard ratio (HR) and 95% confidence interval (CI). Results: All patients were divided into three groups: died from localized PCa (n=1,400), died from other causes (n=16,996), and survived (n=116,914). The diagnostic age of 119,899 patients was ≥55 years. The multivariate Fine-Gray analysis indicated that age of diagnosis (55-70 years: HR =1.473, 95% CI: 1.124-1.930; >70 years: HR =2.528, 95% CI: 1.901-3.362), race (American India/Alaska Native, Asian/Pacific Islander: HR =0.653, 95% CI: 0.490-0.870), marital status (divorced: HR =1.433, 95% CI: 1.197-1.717; single: HR =1.463, 95% CI: 1.244-1.719; widowed: HR =1.485, 95% CI: 1.222-1.804), therapeutic method (radiotherapy: HR =1.500; 95% CI: 1.119-2.011), SES (4-10: HR =0.799, 95% CI: 0.664-0.961; ≥11: HR =0.670; 95% CI: 0.534-0.839), AJCC stage (HR =0.820, 95% CI: 0.715-0.940), level of PSA (HR: 1.002, 95% CI: 1.002-1.002) and Gleason score (HR: 2.226, 95% CI: 2.108-2.350) were associated with the risk of localized PCa mortality. Conclusions: The study determined the influencing factors for mortality in patients with localized PCa through a competitive risk model. This finding may provide a reference for localized PCa patients: localized PCa patients who are older, divorced, widowed, single, have a radiotherapy, have a high PSA level, and Gleason score may be at high risk.

Predictive model for urosepsis in patients with Upper Urinary Tract Calculi based on ultrasonography and urinalysis using artificial intelligence learning.

PURPOSE: To construct a predicting model for urosepsis risk for patients with upper urinary tract calculi based on ultrasound and urinalysis. MATERIALS AND METHODS: A retrospective study was conducted in patients with upper urinary tract calculi admitted between January 2016 and January 2020. The patients were randomly grouped into the training and validation sets. The training set was used to identify the urosepsis risk factors and construct a risk prediction model based on ultrasound and urinalysis. The validation set was used to test the performance of the artificial neural network (ANN). RESULTS: Ultimately, 1716 patients (10.8% cases and 89.2% control) were included. Eight variables were selected for the model: sex, age, body temperature, diabetes history, urine leukocytes, urine nitrite, urine glucose, and degree of hydronephrosis. The area under the receiver operating curve in the validation and training sets was 0.945 (95% CI: 0.903-0.988) and 0.992 (95% CI: 0.988-0.997), respectively. Sensitivity, specificity, and Yuden index of the validation set (training set) were 80.4% (85.9%), 98.2% (99.0%), and 0.786 (0.849), respectively. CONCLUSIONS: A preliminary screening model for urosepsis based on ultrasound and urinalysis was constructed using ANN. The model could provide risk assessments for urosepsis in patients with upper urinary tract calculi.

Metabolic dysfunction-associated fatty liver disease and cardiovascular disease: A meta-analysis.

Background: Metabolic dysfunction-associated fatty liver disease [MAFLD, formerly known as nonalcoholic fatty liver disease (NAFLD)] is one of the most important causes of liver disease worldwide, while cardiovascular disease (CVD) is still one of the main causes of morbidity and mortality worldwide, and the two are closely related. This study aimed to investigate the risk of CVD incidence or CVD-related mortality (CVD mortality) in patients diagnosed with MAFLD under new concepts and new diagnostic criteria. Methods: We searched English databases PubMed, Web of Science, Embase, and Cochrane Library for relevant literature. The language was restricted to English. Results: By 22 January 2022, 556 published studies were obtained through preliminary retrieval, and 10 cohort studies were included in this study. All statistical analyses were performed using Review Manager 5.2 software. Compared with the control group, patients in the MAFLD group had a significantly higher relative risk of CVD incidence or CVD mortality during the follow-up, with an RR rate of 1.95 (95% CI 1.76-2.17, p < 0.01). The incidence of CVD in the MAFLD group was more than twice that in the control group (RR 2.26, 95% CI 2.00-2.54, p < 0.01). The mortality rate of CVD was 1.57 times higher than that in the control group (RR 1.57, 95% CI 1.42-1.72, p < 0.01). Conclusions: Patients diagnosed with MAFLD alone had higher cardiovascular mortality than those diagnosed with NAFLD alone based on the available data.

Efficacy and safety of outpatient parenteral antibiotic therapy in patients with infective endocarditis: a meta-analysis / Eficacia y seguridad del tratamiento antibiótico domiciliario endovenoso en pacientes con endocarditis infecciosa: un metaanálisis

Background. To investigate the clinical outcome of patients with infective endocarditis (IE) during and after outpatient parenteral antimicrobial treatment (OPAT), and to furtherclarify the safety and efficacy of OPAT for IE patients.Methods. Through December 20, 2021, a total of 331 articles were preliminarily searched in Pubmed, Web of Science,Cochrane Library and Embase, and 9 articles were eventuallyincluded in this study.Results. A total of 9 articles comprising 1,116 patientswere included in this study. The overall mortality rate of patients treated with OPAT was 0.04 (95% CI, 0.02-0.07), thatmeans 4 deaths per 100 patients treated with OPAT. Separately, mortality was low during the follow-up period after OPATtreatment, with an effect size (ES) of 0.03 (95%CI, 0.02-0.07)and the mortality of patients during OPAT treatment was 0.04(95% CI, 0.01-0.12). In addition, the readmission rate wasfound to be 0.14 (95% CI, 0.09-0.22) during the follow-upand 0.18 (95% CI, 0.08-0.39) during treatment, and 0.16 (95%CI, 0.10-0.24) for patients treated with OPAT in general. Regarding the relapse of IE in patients, our results showed a lowoverall relapse rate, with an ES of 0.03 (95% CI, 0.01-0.05). Inaddition, we found that the incidence of adverse events waslow, with an ES of 0.26 (95% CI, 0.19-0.33). (AU)

Introducción. Investigar el resultado clínico de los pacientes con endocarditis infecciosa (EI) durante y después deltratamiento antibiótico domiciliario endovenoso (TADE), y determinar la seguridad y eficacia del TADE para los pacientescon EI.Métodos. Hasta el 20 de diciembre de 2021, se realizaronbúsquedas preliminares en un total de 331 artículos en Pubmed, Web of Science, Cochrane Library y Embase, y finalmente se incluyeron 9 artículos en este estudio.Resultados. Se incluyeron un total de 9 artículos con1.116 pacientes. La tasa de mortalidad global de los pacientestratados con TADE fue de 0,04 (IC95%: 0,02-0,07), lo que significa 4 muertes por cada 100 pacientes tratados con TADE.Por separado, la mortalidad fue baja durante el período deseguimiento después del tratamiento con TADE, con un tamaño del efecto (TE) de 0,03 (IC95%: 0,02-0,07) y la mortalidadde los pacientes durante el tratamiento con TADE fue de 0,04(IC95%: 0,01-0,12). Además, se encontró que la tasa de readmisión fue de 0,14 (IC95%: 0,09-0,22) durante el seguimiento y de 0,18 (IC95%: 0,08-0,39) durante el tratamiento, y de 0,16 (IC95%: 0,10-0,24) para los pacientes tratados con TADEde forma global. En cuanto a la recaída de la EI en pacientes,nuestros resultados mostraron una baja tasa global de recaída, con un TE de 0,03 (IC95%: 0,01-0,05). Además, se encontróque la incidencia de eventos adversos fue baja, con una TE de0,26 (IC95%: 0,19-0,33). (AU)

[Clinical analysis of early damage in multiple extra-pulmonary organs in COVID-19].

OBJECTIVE: To analyze the clinical manifestations of heart, liver and kidney damages in the early stage of COVID-19 to identify the indicators for these damages. METHODS: We analyzed the clinical features, underlying diseases, and indicators of infection in 12 patients with COVID-19 on the second day after their admission to our hospital between January 20 and February 20, 2020.The data including CK-MB, aTnI, BNP, heart rate, changes in ECG, LVEF (%), left ventricular general longitudinal strain (GLS, measured by color Doppler ultrasound) were collected.The changes of liver function biochemical indicators were dynamically reviewed.BUN, UCR, eGFR, Ccr, and UACR and the levels of MA, A1M, IGU, and TRU were recorded. RESULTS: The 12 patients included 2 severe cases, 8 common type cases, and 2 mild cases.Four of the patients presented with sinus tachycardia, ECG changes and abnormal GLS in spite of normal aTNI and LVEF; 1 patient had abnormal CKMB and BNP.On the first and third days following admission, the patients had normal ALT, AST and GGT levels.On day 7, hepatic function damage occurred in the severe cases, manifested by elevated ALT and AST levels.Abnormalities of eGFR, Ccr and UACR occurred in 8, 5 and 5 of the patients, respectively.Abnormal elevations of MA, A1M, IGU and TRU in urine protein were observed in 4, 4, 5, and 2 of the patients, respectively. CONCLUSIONS: In patients with COVID-19, heart damage can be identified early by observing the GLS and new abnormalities on ECG in spite of normal aTNI and LVEF.Early liver injury is not obvious in these patients, but dynamic monitoring of the indicators of should be emplemented, especially in severe cases. In cases with normal CR and BUN, kidney damage can be detected early by calculating eGFR, Ccr and UACR and urine protein tests.

Characteristics of Renal Function in Patients Diagnosed With COVID-19: An Observational Study.

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

Comparison of meatal-based flap (Mathieu) and tubularized incised-plate (TIP) urethroplasties for primary distal hypospadias: A systematic review and meta-analysis.

PURPOSE: We conducted this meta-analysis to compare postoperative outcomes between meatal-based flap (Mathieu) and tubularized incised plate (TIP) techniques for distal hypospadias. METHODS: A comprehensive literature search of PUBMED, Web of Science, EMBASE, and Cochrane Library was conducted. Outcomes evaluated in this review were fistula, meatal stenosis, wound dehiscence and flap necrosis. We calculated odds ratio (OR) with 95% confidential interval (CI) to compare postoperative outcomes between Mathieu and TIP after data extraction and literature identification. All data were analyzed using Review Manager 5.2. In order to find potential affective factors, meta-regression and subgroup analyses were applied. RESULTS: 16 studies, 1386 patients, including 762 patients receiving Mathieu and 624 individuals subjected to TIP met the inclusion criteria. The synthetic data suggested that Mathieu and TIP were comparable in terms of fistula (OR = 0.93; 95% CI: 0.65 to 1.33; P = 0.70, I2 = 14%), wound dehiscence (OR = 0.89; 95% CI: 0.33 to 2.39; P = 0.81, I2 = 11%), and flap necrosis (OR = 1.9; 95% CI: 0.51 to 7.09; P = 0.20, I2 = 38%) without significant heterogeneity for each comparison group. Pooled estimates showed a significantly lower rate of meatal stenosis with Mathieu than with TIP (OR = 0.41; 95% CI: 0.24 to 0.73; P = 0.002, I2 = 4%). Subgroup analyses showed that the difference between Mathieu and TIP was more obvious in the studies published before 2013 in meatal stenosis. The modified Mathieu technique and a running suture for urethroplasty might be relevant to a lower rate of meatal stenosis in the data, although no statistical significance in the present effects model overall was found. One-way sensitivity analysis showed that the results were stable. There was no publication bias detected using both funnel plot and Egger's test. CONCLUSION: This meta-analysis suggested that Mathieu and TIP technique were equivalent for primary distal hypospadias in terms of fistula, wound dehiscence, and flap necrosis. Pooled estimates indicated that there was a lower rate of meatal stenosis with Mathieu rather than with TIP significantly. The modified Mathieu technique and a running suture for urethroplasty might be relevant to a lower rate of meatal stenosis. TYPE OF STUDY: Meta-analysis. LEVEL OF EVIDENCE: IV.

No significant association between immunosuppression in solid organ transplantation and prostate cancer risk: a meta-analysis of cohort studies.

BACKGROUND: It is known that organ transplant recipients have a significantly higher risk for developing cancers, but the association between immunosuppression in organ transplantation and the risk for prostate cancer (PCa) remains unclear. We aimed to assess the evidence regarding the association of solid organ transplantation with PCa risk. METHODS: A literature search of the PubMed, Embase, and Web of Science databases was performed up to March 2019. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using a fixed-effect or random-effect model. RESULTS: In total, 26 articles including 33 independent population-based cohort studies with 556,812 recipients and 2,438 PCa cases were identified and included in this meta-analysis. PCa risk in the solid organ transplant recipients did not increase compared with the general population (RR=1.04; 95% CI: 0.90-1.18). Independent analysis of different kinds of organ replacements further indicated immune inhibition in the transplantation of kidney, liver, heart, and lung, and was not associated with elevated PCa risk (RR=0.89; 95% CI: 0.83-0.95; RR=0.61, 95% CI: 0.21-1.02; RR=1.70, 95% CI: 0.88-2.52; RR=0.87, 95% CI: 0.57-1.16, respectively). CONCLUSIONS: This study demonstrated that immunosuppression in solid organ transplant recipients was not associated with higher PCa risk.

The Effect of Daily Fluid Management and Beverages Consumption on the Risk of Bladder Cancer: A Meta-analysis of Observational Study.

Epidemiological studies have evaluated the risk of bladder cancer (BCa) in relation to total fluid intake, as well as specific type of beverages consumption, with controversial results. The aim of this study was to further explore the potential relationship by conducting a meta-analysis. Fifty-four articles involving more than 43,000 BCa patients were included in this meta-analysis. A positive, though not statistically significant, association was found between total fluid intake and risk of BCa comparing the highest with lowest intake (SRRE: 1.16, 95%CI: 1.00-1.36). By conducting dose-response meta-analysis, we found that each 500 ml/day increase in total fluid intake was associated with 3.3% increased risk of BCa (RR: 1.03, 95%CI: 1.00-1.07). Pronounced increase in risk of BCa was detected when total fluid intake was more than 3000 ml/day. Meta-analyses of specific type of beverages showed increasing intake of coffee (RR: 1.03, 95%CI: 1.02-1.05) were risk factors for BCa. On the contrary, increasing intake of milk appeared to be a potential protective factor for BCa (RR: 0.90, 95%CI: 0.83-0.98). The risk of BCa was not significantly related to intake of water (RR: 1.01, 95%CI: 0.98-1.03), alcohol (RR: 1.01, 95%CI: 0.97-1.05), tea (RR: 1.01, 95%CI: 0.97-1.05) and soft drinks (RR: 1.04, 95%CI: 0.96-1.11).

Association of smoking status with prognosis in bladder cancer: A meta-analysis.

There is considerable controversy regarding the association between smoking and prognosis in surgically treated bladder cancer. The present meta-analysis was performed to quantify the role of smoking status in bladder cancer recurrence, progression and patient survival by pooling the available previous data. Pubmed, Embase and the Cochrane Library databases were searched for eligible studies published prior to April 2016. Random and fixed effects models were used to calculate the summary relative risk estimates (SRRE). A total of 10,192 patients from 15 studies were included in the meta-analysis. There was evidence of positive associations between current smoking and the risk of recurrence (SRRE=1.23; 95% CI, 1.05-1.45) and mortality (SRRE=1.28; 95% CI, 1.07-1.52) in bladder cancer. Furthermore, former smoking had positive associations with bladder cancer recurrence (SRRE=1.22; 95% CI, 1.09-1.37) and mortality (SRRE=1.20; 95% CI, 1.03-1.41). However, there was no significant association between bladder cancer progression risk and current (SRRE=1.11; 95% CI, 0.71-1.75) or previous smoking (SRRE=1.16; 95% CI, 0.92-1.46). The findings indicate that current and former smoking increase the risk of recurrence and mortality in patients with bladder cancer. However, due to the nonrandomized and retrospective nature of the current study, patients may be prone to potential selection bias. Prospective and larger epidemiological studies with a longer follow-up are required to confirm these findings.

Impact of surgical margin status on the outcome of bladder cancer treated by radical cystectomy: a meta-analysis.

Data regarding the association between surgical margin status and the outcome of bladder cancer treated by radical cystectomy (RC) are conflicting. Therefore, the present meta-analysis was performed to assess the associations between the outcomes of bladder cancer, in terms of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS), and the presence of positive surgical margins versus negative surgical margins following treatment with RC. Research articles published prior to April 2016 were identified from Pubmed, Embase and the Cochrane Library databases. A total of 36 articles were included, with a sample size of 38,384 bladder cancer patients. Of these, 4,354 patients were reported to have positive surgical margins. Significant associations were detected between positive surgical margins following RC and unfavorable RFS [summary relative risk estimate (SRRE), 1.63; 95% confidence interval (CI), 1.46-1.83; P = 0.105], CSS (SRRE, 1.82; 95% CI, 1.63-2.04; P = 0.001) and OS (SRRE, 1.68; 95% CI, 1.58-1.80; P = 0.805), by fixed or random effects models. The findings were consistent independently of age, sample size, publication year, follow-up duration, study type and geographical region. In summary, the present findings demonstrate that the presence of positive surgical margins is associated with poor survival outcomes in bladder cancer following RC, indicating that avoidance of positive surgical margins during surgery is helpful to improve the prognosis of patients with bladder cancer.

A greater number of dissected lymph nodes is associated with more favorable outcomes in bladder cancer treated by radical cystectomy: a meta-analysis.

The optimal extent of lymph node dissection (LND) is currently not established, and the debate regarding the association between the number of dissected nodes and the outcomes of bladder cancer treated by radical cystectomy (RC) is still ongoing. Therefore, the present meta-analysis was performed to clarify this potential relationship. Eligible studies were retrieved via an electronic search for studies published up to April 2016, and by manual review of the references. A total of 25 cohort studies involving 41,400 bladder cancer patients who underwent RC were included. The summary relative risk estimates (SRRE) based on the highest compared with the lowest categories of LND were estimated by variance-based meta-analysis. Heterogeneity among the study results was explored through stratified analyses. Overall, bladder cancer patients with the highest category of LND had 28%, 34% and 36% reduced risks, corresponding to overall survival (SRRE = 0.72; 95% CI, 0.64-0.80), cancer-specific survival (SRRE = 0.66; 95% CI, 0.54-0.80) and recurrence-free survival (SRRE = 0.64; 95% CI, 0.50-0.82), respectively, compared with patients with the lowest category of LND. In summary, the patients with a greater number of dissected lymph nodes had statistically significant survival advantages in terms of the outcomes of bladder cancer following RC. The number of dissected lymph nodes could be an independent prognostic factor for bladder cancer. These findings need to be validated in prospective and larger epidemiological studies with a longer follow-up period.

Prognostic value of cytoreductive nephrectomy combined with targeted therapy for metastatic renal cell carcinoma: a meta-analysis.

PURPOSE: The role of cytoreductive nephrectomy (CN) has been controversial with the advent of targeted therapy. Our study was to identify the prognostic value of CN combined with targeted therapy for treatment of metastatic renal cell carcinoma (mRCC) by conducting a meta-analysis based on the existing population-based studies. METHODS: Research articles published up to September 2015 were searched through PubMed and Embase. A meta-analysis was performed to assess the overall survival (OS) and progression-free survival (PFS) of patients with mRCC undergoing CN combined with targeted therapy compared with targeted therapy alone. Furthermore, analysis was made to evaluate some potential prognostic factors predicting survival. RESULTS: Eight studies were included in our analysis with 2688 mRCC patients. A fixed-effect model was performed and found the pooled HR of OS was 0.60 (95 % CI 0.53-0.67, p < 0.0001). Furthermore, the pooled median survival ratio was elevated (HR 2.11, 95 % CI 1.78-2.49, p < 0.0001), indicating that patients who received CN combined with targeted therapy yielded a more than twofold prolonged OS compared with those who received targeted therapy alone. Moreover, no significant difference was observed in PFS in the patients undergoing CN combined with targeted therapy (HR 0.82, 95 % CI 0.57-1.19, p = 0.30). CONCLUSIONS: Current evidence suggests that CN combined with targeted therapy has a significant OS advantage in patients with mRCC. However, the results should be evaluated in the context of the potential selection biases of the existing evidence. Large prospective cohort studies are required to confirm these findings.