Intravesical Pseudomonas aeruginosa mannose-sensitive Hemagglutinin vaccine triggers a tumor-preventing immune environment in an orthotopic mouse bladder cancer model.

Bacillus Calmette-Guerin (BCG) immunotherapy can prevent recurrence and progression in selected patients with non-muscle-invasive bladder cancer (NMIBC); however, significant adverse events and treatment failure suggest the need for alternative agents. A commercial anti-infection vaccine comprises a genetically engineered heat-killed Pseudomonas aeruginosa (PA) expressing many mannose-sensitive hemagglutination (MSHA) fimbriae, termed PA-MSHA, which could be a candidate for bladder cancer intravesical therapy. In an immunocompetent orthotopic MB49 bladder cancer model, we characterized the antitumor effects and mechanisms of PA-MSHA compared with those of BCG. Three weekly intravesical PA-MSHA or BCG treatments reduced tumor involvement; however, only PA-MSHA prolonged survival against MB49 implantation significantly. In non-tumor-bearing mice after treatment, flow-cytometry analysis showed PA-MSHA and BCG induced an increased CD4/CD8 ratio, the levels of effector memory T cell phenotypes (CD44, CXCR-3, and IFN-γ), and the proportion of CD11b+Ly6G-Ly6C-IA/IE+ mature macrophages, but a decrease in the proportion of CD11b+Ly6G-Ly6C+IA/IE- monocytic myeloid-derived suppressor cells (Mo-MDSCs) and the expression of suppressive molecules on immune cells (PD-L1, PD-1, TIM-3, and LAG-3). Notably, PA-MSHA, but not BCG, significantly reduced PD-1 and TIM-3 expression on CD4+ T cells, which might account for the better effects of PA-MSHA than BCG. However, in tumor-bearing mice after treatment, the increased proportion of Mo-MDSCs and high expression of PD-L1 might be involved in treatment failure. Thus, modulating the balance among adaptive and innate immune responses was identified as a key process underlying PA-MSHA-mediated treatment efficacy. The results demonstrated mechanisms underlying intravesical PA-MSHA therapy, pointing at its potential as an alternative effective treatment for NMIBC.

Development of a radiomics model to diagnose pheochromocytoma preoperatively: a multicenter study with prospective validation.

BACKGROUND: Preoperative diagnosis of pheochromocytoma (PHEO) accurately impacts preoperative preparation and surgical outcome in PHEO patients. Highly reliable model to diagnose PHEO is lacking. We aimed to develop a magnetic resonance imaging (MRI)-based radiomic-clinical model to distinguish PHEO from adrenal lesions. METHODS: In total, 305 patients with 309 adrenal lesions were included and divided into different sets. The least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction, feature selection, and radiomics signature building. In addition, a nomogram incorporating the obtained radiomics signature and selected clinical predictors was developed by using multivariable logistic regression analysis. The performance of the radiomic-clinical model was assessed with respect to its discrimination, calibration, and clinical usefulness. RESULTS: Seven radiomics features were selected among the 1301 features obtained as they could differentiate PHEOs from other adrenal lesions in the training (area under the curve [AUC], 0.887), internal validation (AUC, 0.880), and external validation cohorts (AUC, 0.807). Predictors contained in the individualized prediction nomogram included the radiomics signature and symptom number (symptoms include headache, palpitation, and diaphoresis). The training set yielded an AUC of 0.893 for the nomogram, which was confirmed in the internal and external validation sets with AUCs of 0.906 and 0.844, respectively. Decision curve analyses indicated the nomogram was clinically useful. In addition, 25 patients with 25 lesions were recruited for prospective validation, which yielded an AUC of 0.917 for the nomogram. CONCLUSION: We propose a radiomic-based nomogram incorporating clinically useful signatures as an easy-to-use, predictive and individualized tool for PHEO diagnosis.

Detection of liver metastases on gadobenate dimeglumine-enhanced MRI: systematic review, meta-analysis, and similarities with gadoxetate-enhanced MRI.

OBJECTIVES: To determine the sensitivity and positive predictive value (PPV) of gadobenate-enhanced MR imaging for the detection of liver metastases. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines. A comprehensive search (EMBASE, PubMed) was performed to identify relevant articles up to December 2017. Studies eligible for inclusion were performed using appropriate methodology with complete verification by means of histopathology, intraoperative observation and/or follow-up, and sufficient information to permit determination of true-positive (TP), false-negative (FN), and false-positive (FP) values. Sources of bias were assessed using the QUADAS-2 tool. An inverse variance-weighted random-effects model was used to obtain sensitivity and PPV estimates. Information was analyzed and presented using Cochran's Q statistic, funnel plots, and modified Deeks' analysis. RESULTS: Ten articles (256 patients, 562 metastases) were included. Sensitivity estimates for pre-contrast (unenhanced) imaging, gadobenate-enhanced dynamic imaging, and combined unenhanced, dynamic, and delayed hepatobiliary phase imaging for detecting liver metastases on a per-lesion basis were 77.8% (95% CI 71.4-84.3%, 7 assessments), 88.1% (95% CI, 84.0-92.2%, 13 assessments), and 95.1% (95% CI 93.1-97.1%, 15 assessments), respectively. The addition of hepatobiliary phase images significantly improved the detection of liver metastases. The overall PPV was 90.9% (95% CI 86.6-95.1%, 11 assessments). Deeks' funnel analysis revealed no association between sample size and sensitivity (ß = 0.02, p = 0.814) indicating no significant publication bias. CONCLUSIONS: Gadobenate-enhanced MR imaging has high sensitivity and PPV for the detection of liver metastases on a per-lesion basis. The sensitivity and PPV for detection is comparable to reported values for the pure liver-specific agent gadoxetate. KEY POINTS: • Gadobenate dimeglumine is a hepatobiliary MR contrast agent that permits acquisition of contrast-enhanced liver images during the immediate post-injection dynamic phase, like any extracellular agent, and in the delayed hepatobiliary phase, after specific uptake by the hepatocytes. • The hepatobiliary phase improves detection of liver metastases when compared either to pre-contrast unenhanced images alone or to pre-contrast + gadobenate-enhanced dynamic phase images. • The meta-analysis showed an overall sensitivity of 95.1% and PPV of 90.9% of gadobenate-enhanced MRI for the detection of metastases, when based on the evaluation of all available acquisitions.

Laparoscopic Partial Nephrectomy for T1 Renal Cell Carcinoma: Comparison of Two Resection Techniques in a Multi-institutional Propensity Score-Matching Analysis.

BACKGROUND: Enucleoresection is defined as presence of a minimal paratumor parenchyma that allows for clear visualization of the tumor's contours during partial nephrectomy (PN). Because there is variability in published reports regarding resection techniques during PN before the surface-intermediate-base (SIB) margin score reporting system, the association between postoperative outcomes and resection techniques are rarely reported. This study was designed to compare the perioperative, oncologic, and functional outcomes between laparoscopic enucleoresection (LER) (SIB score 1 + 1 + 1 = 3) and traditional laparoscopic partial nephrectomy (TLPN) (SIB score 1 + 2 + 2 = 5). METHODS: Data from 270 consecutive patients who underwent laparoscopic partial nephrectomy for single T1 RCC at 3 medical centers were prospectively collected. Propensity score matching was performed on age, gender, body mass index, American Society of Anesthesiologists score, preoperative estimated glomerular filtration rate (eGFR), tumor size, RENAL nephrometry score, Charlson score, and solitary kidney status. Normal parenchyma width of each patient was evaluated right after the surgery, and SIB score was assigned retrospectively. Ninety-eight matched patients undergoing LER or TLPN were compared for perioperative, oncologic, and functional outcomes. RESULTS: After matching, warm ischemia time (WIT) and operative time were significantly shorter in LER than TLPN group (20.8 vs. 23.8 min, P = 0.003 and 130.8 vs. 152.1 min, P = 0.005, respectively). Estimated blood loss (EBL) also was lower in LER than TLPN group (50 vs. 90 mL, P = 0.045). Complication rates, positive surgical margin rates, and local recurrence rates were comparable between groups (P = 0.3, P = 0.62, and P = 1.0, respectively). At last follow-up, the eGFRs also were comparable in both groups (P = 0.6). CONCLUSIONS: LER has similar oncologic, functional outcomes and complication rates with the advantage of a shorter WIT, operative time, and lower EBL compared with TLPN.

Extended vs non-extended pelvic lymph node dissection and their influence on recurrence-free survival in patients undergoing radical cystectomy for bladder cancer: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To compare extended pelvic lymph node dissection (ePLND) with non-extended pelvic lymph node dissection (non-ePLND) and assess their influence on recurrence-free survival (RFS) in patients undergoing radical cystectomy for bladder cancer. METHODS: Through a comprehensive search of the PubMed, Embase and Cochrane Library databases in September 2012, we performed a systematic review and cumulative meta-analysis of all comparative studies assessing the extent of pelvic lymph node dissection (PLND) and its influence on RFS. RESULTS: Six studies with a total of 2824 patients were identified. Overall analysis showed a significantly better RFS rate in patients who had undergone ePLND than in those who had undergone non-ePLND (hazard ratio [HR]: 0.65; P < 0.001). A subgroup analysis found that, compared with non-ePLND, ePLND was associated with a better RFS rate for both patients with negative lymph nodes (HR: 0.68; P = 0.007) and those with positive lymph nodes (HR: 0.58; P < 0.001). When stratified by pathological T stage, ePLND provided additional RFS benefits for patients with pT3-4 disease (HR: 0.61; P < 0.001), but not for patients with ≤pT2 disease (HR: 0.95; P = 0.81). CONCLUSIONS: The results of this meta-analysis indicate that ePLND provides a RFS benefit compared with non-ePLND. On subgroup analysis, ePLND provides better RFS not only for patients who had positive lymph nodes and pT3-4 disease, but also for patients with negative lymph nodes. Two randomized controlled trials on ePLND vs non-ePLND are awaited which should provide more clinically meaningful results.

Assessing the predictive value of smoking history for immunotherapy outcomes in bladder cancer patients.

Background: The therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in bladder cancer varies among individuals. Identifying reliable predictors of response to these therapies is crucial for optimizing patient outcomes. Methods: This retrospective study analyzed 348 bladder cancer patients treated with ICIs, with additional validation using data from 248 patients at our institution who underwent PD-L1 immunohistochemical staining. We examined patient smoking history, clinicopathological characteristics, and immune phenotypes. The main focus was the correlation between smoking history and immunotherapy outcomes. Multivariate logistic and Cox proportional hazard regressions were used to adjust for confounders. Results: The study cohort comprised 348 bladder cancer patients receiving ICIs. Among them, 116 (33.3%) were never smokers, 197 (56.6%) were former smokers (median pack-years = 28), and 35 (10.1%) were current smokers (median pack-years = 40). Analysis revealed no statistically significant difference in overall survival across different smoking statuses (objective response rates were 11.4% for current smokers, 17.2% for never smokers, and 22.3% for former smokers; P = 0.142, 0.410, and 0.281, respectively). However, a notable trend indicated a potentially better response to immunotherapy in former smokers compared to current and never smokers. In the validation cohort of 248 patients from our institution, immunohistochemical analysis showed that PD-L1 expression was significantly higher in former smokers (55%) compared to current smokers (37%) and never smokers (47%). This observation underscores the potential influence of smoking history on the tumor microenvironment and its responsiveness to ICIs. Conclusion: In conclusion, our study demonstrates the importance of incorporating smoking history in predicting the response to immunotherapy in bladder cancer patients, highlighting its role in personalized cancer treatment approaches. Further research is suggested to explore the comprehensive impact of lifestyle factors on treatment outcomes.

Estimation of the tumor size at cure threshold among adult patients with adrenocortical carcinoma: A populational-based study.

Background: The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients. Methods: The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The "X-Tile" program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively. Results: A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using X-tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (＞8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, P < 0.001). Subgroup analyses revealed no statistical significance and a consistent proportionate effect of tumor size on CSS and OS across all eight pre-specified subgroups. Interestingly, an additional subgroup analysis showed that ACC patients could not benefit from chemotherapy in terms of CSS and OS. Conclusion: The study suggests that tumor size is a crucial prognostic factor in ACC patients and a cutoff value 8.5 cm might indicate a poor outcome. Given the limitations of the available data, it is challenging to conclusively determine the benefit of chemotherapy in adult ACC patients across different tumor size ranges.

Type III interferon inhibits bladder cancer progression by reprogramming macrophage-mediated phagocytosis and orchestrating effective immune responses.

BACKGROUND: Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated. METHODS: We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells' infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate. RESULTS: In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G-Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy. CONCLUSIONS: Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis.

This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.

Optimal frequency of shock wave lithotripsy in urolithiasis treatment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The optimal frequency of shock wave lithotripsy in urolithiasis has not been well determined. MATERIALS AND METHODS: A search of MEDLINE, Web of Science and the Cochrane Library was performed. All randomized controlled trials including articles and meeting abstracts that compared the effects of different frequencies (120, 90 and 60 shock waves per minute) of shock wave lithotripsy were included in analysis. The review process followed the guidelines of the Cochrane Collaboration. RESULTS: Nine randomized controlled trials including 1,572 cases were identified. Overall success rates and success rates for large stones (greater than 10 mm) were significantly lower in the 120 vs 60 (p <0.001 and p = 0.002, respectively) and in the 120 vs 90 (p <0.001 and p = 0.02, respectively) shock waves per minute groups, but similar between the 90 and 60 shock waves per minute groups. Treatment duration was significantly shorter in the 120 vs 60, 120 vs 90 and 90 vs 60 shock waves per minute groups (all p <0.001). Success rates for small stones (less than 10 mm), complication rates and total shock waves had no significant differences among the 3 groups. CONCLUSIONS: Decreasing the frequency from 120 to 60 shock waves per minute increased overall success rates. While the treatment duration of 60 shock waves per minute was much greater, 90 shock waves per minute seemed to be optimal, especially for large stones. A frequency of 120 shock waves per minute might still be recommended for small stones.

Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: a global systematic review and meta-analysis.

BACKGROUND: Laparoscopic hepatectomy (LH) has been proposed as a safe and feasible treatment option for liver diseases. However, the short- and long-term outcomes of LH versus open hepatectomy (OH) for hepatocellular carcinoma (HCC) have not been adequately assessed. Thus, as another means of surgical therapy for hepatocellular carcinoma (HCC), we assessed the feasibility of performing LH as the standard procedure for disease in the left lateral lobe and peripheral right segments for HCC in selected patients. METHODS: Literature search included PubMed, Embase, Science Citation Index, SpringerLink, and secondary sources, from inception to March 2012, with no restrictions on languages or regions. The fixed-effects and random-effects models were used to measure the pooled estimates. The test of heterogeneity was performed by the Q statistic. Subgroup and sensitivity analyses were performed to explore heterogeneity between studies and to assess the effects of study quality. RESULTS: A total of 1238 patients (LH 485, OH 753) from 15 studies were included. The pooled odds ratios for postoperative morbidity and incidence of negative surgical margin in LH were found to be 0.37 (95 % confidence interval [CI] 0.27-0.52; P < 0.01) and 1.63 (95 % CI 0.82-3.22; P = 0.16), respectively, compared with OH. Blood loss was significantly decreased in the LH (weighted mean difference -224.63; 95 % CI -384.87 to -64.39; P = 0.006). No significant difference was observed between the both groups for long-term outcomes of overall survival and recurrence-free survival. CONCLUSIONS: In patients with solitary left lateral lobe/right peripheral subcapsular tumors treated with minor resection, this meta-analysis demonstrated that compared to OH, LH may have short-term advantages in terms of blood loss and postoperative morbidity for HCC. Both procedures have similar long-term outcomes. It may be time to consider changing the standard procedures for treatment of HCC in the left lateral lobe and peripheral subcapsular right segments in selected patients.

Comparison of transperitoneal and retroperitoneal laparoscopic nephrectomy for renal cell carcinoma: a systematic review and meta-analysis.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Laparoscopic nephrectomy is now considered to be the reference procedure for kidney cancer. It can be performed via a transperitoneal or retroperitoneal approach. Each approach has its advantages and disadvantages. No definitive conclusions regarding objective difference between the two approaches have been reached to date. This meta-analysis indicates that in appropriately selected patients, especially patients with posteriorly located renal tumors, the retroperitoneal approach may be faster and equally safe compared with the transperitoneal approach. OBJECTIVE: To evaluate the efficiency and safety of the retroperitoneal and transperitoneal approaches in laparoscopic radical/partial nephrectomy (RN/PN) for renal cell carcinoma. METHODS: A systematic search of PUBMED, EMBASE, and the Cochrane Library was performed to identify prospective randomized controlled trials and retrospective observational studies that compared the outcomes of the two approaches. Outcomes of interest included perioperative and postoperative variables, surgical complications and oncological variables. RESULTS: Twelve studies assessing transperitoneal laparoscopic RN (TLRN) vs retroperitoneal laparoscopic RN (RLRN) and six studies assessing transperitoneal laparoscopic PN (TLPN) vs retroperitoneal laparoscopic PN (RLPN) were included. The RLRN approach had a shorter time to renal artery control (weighted mean difference [WMD] 68.65 min; 95% confidence interval [CI] 40.80-96.50; P < 0.001) and a lower overall complication rate (odds ratio 2.12; 95% CI 1.30-3.47; P = 0.003) than TLRN. RLPN had a shorter operating time (WMD 48.85 min; 95% CI 29.33-68.37; P < 0.001) and a shorter length of hospital stay (WMD 1.01 days; 95% CI 0.39-1.63; P = 0.001) than TLPN. There were no significant differences between the retroperitoneal and transperitoneal approaches in other outcomes of interest. CONCLUSIONS: This meta-analysis indicates that, in appropriately selected patients, especially patients with posteriorly located renal tumours, the retroperitoneal approach may be faster and equally safe compared with the transperitoneal approach. Despite our rigorous methodology, conclusions drawn from our pooled results should be interpreted with caution because of the inherent limitations of the included studies.

Diagnosis of narrow-band imaging in non-muscle-invasive bladder cancer: a systematic review and meta-analysis.

OBJECTIVES: The objective was to evaluate the diagnostic accuracy of cystoscopy assisted by narrow-band imaging compared with white-light imaging for non-muscle-invasive bladder cancer. METHODS: An electronic database search of PubMed, Embase, the Cochrane Library, Ovid and Web of Science was carried out for all articles comparing narrow-band imaging with white-light imaging cystoscopy in the detection of non-muscle-invasive bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. RESULTS: Seven studies with prospectively collected data including a total of 1040 patients were identified, and 611 patients with 1476 tumors were detected by biopsy. In the patient- and tumor-level analysis, an additional 17% of patients (95% confidence interval, 10-25%) and an additional 24% of tumors (95% confidence interval, 17-31%) were detected by narrow-band imaging, respectively. In the patient- and tumor-level analysis, significantly higher detection rates using narrow-band imaging (rate difference 11%; 95% confidence interval 5-17%; P < 0.001; and rate difference 19%; 95% confidence interval 12-26%; P < 0.001, respectively) rather than white-light imaging were found. On the tumor level, an additional 28% of carcinoma in situ was detected (95% confidence interval 14-45%) by narrow-band imaging, and a significantly higher detection rate (rate difference 11%; 95% confidence interval 1-21%; P = 0.03) was found. The false-positive detection rate of tumor level did not differ significantly between the two techniques. CONCLUSIONS: Cystoscopy assisted by narrow-band imaging detects more patients and tumors of non-muscle-invasive bladder cancer than white-light imaging, and it might be an additional or alternative diagnostic technique for non-muscle-invasive bladder cancer.

Bladder-sparing approaches for muscle invasive bladder cancer: a narrative review of current evidence and future perspectives.

Background and Objective: In recent years, the application of less-invasive "bladder-sparing" trimodal therapy (TMT) in selected muscle-invasive bladder cancer (MIBC) patients unfit for or who declined radical cystectomy (RC) has been increasing. This review aims to summarize the current evidence and future perspectives of bladder-sparing therapy for MIBC. Methods: A non-systematic Medline/PubMed literature search was conducted on July 2022 with the following keywords 'MIBC', 'bladder-sparing', 'chemotherapy', 'radiotherapy', 'trimodal', 'multimodal', and 'immunotherapy'. Key Content and Findings: All monotherapies are inferior to RC or combination therapy and should not be routinely used for curative intent. Radiotherapy (RT) alone has been shown to have poorer outcomes when compared to chemoradiotherapy. The ideal selection criteria for TMT include good bladder function and capacity, clinical stage within cT2, complete transurethral resection of bladder tumor (TURBT), no prior history of pelvic RT, no extensive carcinoma in situ (CIS), and absence of hydronephrosis. The emergence of immunotherapy may further increase the effect of bladder-sparing therapy. Novel predictive biomarkers are awaited for more precise patient selection and better oncological outcomes. Conclusions: TMT is a well-tolerated and offers a curative alternative approach to RC for selected patients with localized MIBC. Appropriate patient selection and a multi-disciplinary approach is crucial in achieving good oncologic control with bladder-sparing therapy.

PD-1/L1 inhibitors can improve but not replace chemotherapy for advanced urothelial carcinoma: A systematic review and network meta-analysis.

Background: Programmed cell death-1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma. Therefore, a comparative evaluation of their efficacy and toxicity compared with chemotherapy is necessary. Methods: We comprehensively searched PubMed, Web of Science, Embase, and Cochrane Library databases and performed a meta-analysis of randomized controlled trials up to July 2021. We considered overall survival as the primary outcome, and progression-free survival, objective response rate, and treatment-related adverse events as secondary outcomes. Results: Overall, 3584 patients from five studies were evaluated. Compared with first-line chemotherapy, programmed cell death-1/ligand 1 inhibitors were significantly associated with worse progression-free survival (p < 0.001) and adverse objective response rates (p < 0.001). However, the treatments were not significantly different in terms of overall survival (p = 0.33). Compared with second-line chemotherapy, programmed cell death-1/ligand 1 inhibitors significantly improved overall survival (p < 0.001), and there was no statistically significant difference in progression-free survival (p = 0.89) or objective response rate (p = 0.34). Compared with chemotherapy, programmed cell death-1/ligand 1 inhibitors were well tolerated (first-line chemotherapy: p < 0.001; second-line chemotherapy: p < 0.001). Conclusions: The efficacy of programmed cell death-1/ligand 1 inhibitors in patients with advanced urothelial carcinoma is not superior to that of first-line platinum-based chemotherapy but is better than second-line chemotherapy; however, programmed cell death-1/ligand 1 inhibitors are safer than first- and second-line chemotherapy and have a broader prospect for use in combination therapy.

Case report: Remarkable response to a novel combination of mitotane, etoposide, paraplatin, and sintilimab in a patient with metastatic adrenocortical carcinoma.

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and limited treatment options for metastases. However, new effective regimens are emerging for specific conditions in metastatic ACC. Case presentation: We report a case of a 36-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (158 mm × 112 mm) and multiple metastases in the liver and lungs. Genetic testing revealed a microsatellite instability-high (MSI-H) tumor, a splice mutation in MLH1, and a high tumor mutational burden (TMB). After the left adrenalectomy, he received sequential treatment with a combination of mitotane, etoposide, paraplatin (EP-M), and sintilimab. His condition has been assessed as a stable disease since the sixth cycle of the combined regimen. Conclusion: This case highlights the remarkable response of our patient's ACC with MSI-H tumor, MLH1 spice mutation, and high TMB to treatment with a novel combination of EP-M and sintilimab. Our findings suggest a promising therapeutic option for patients with similar molecular profiles.

Do disease status and race affect the efficacy of zoledronic acid in patients with prostate cancer? A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Zoledronic acid (ZA) does not improve the overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC); however, little is known about the efficacy of ZA in to hormone-sensitive prostate cancer (HSPC), metastatic hormone-sensitive prostate cancer (mHSPC), and non- metastatic castration-resistant prostate cancer (nmCRPC). Therefore, we assessed the efficacy of ZA in patients with prostate cancer (PCa) and different disease statuses. METHODS: Fifteen eligible randomized-control trials (RCTs) with ZA intervention, including 8280 participants with HSPC, mHSPC, nmCRPC, and mCRPC, were analyzed. The primary and secondary outcome were overall survival(OS), and skeletal-related events (SREs), and bone mineral density (BMD). RESULTS: The participants included 8280 men (7856 non-Asian and 424 Asian). Seven trials yielded a pooled hazard ratio (HR) of 0.95 (0.88, 1.03; P = 0.19) for OS. Subgroup analysis revealed no significant improvement in OS in the HSPC, castration-resistant prostate cancer (CRPC), M0 and M1(bone metastasis) groups, with pooled HR (95%CI) of 0.96 (0.88,1.05), 0.78 (0.46,1.33), 0.95 (0.81,1.13), 0.85 (0.69,1.04) respectively. The Asian group exhibited improved in OS with an HR of 0.67 (0.48, 0.95; P = 0.02), whereas the non-Asian group showed no improvement in OS with an HR of 0.97 (0.90, 1.06; P = 0.52). Five trials yielded pooled odds ratio (OR) of 0.65 (0.45, 0.95; P = 0.02) for SREs. In the subgroup, SREs were significantly decreased in the M1 and Asian groups with ORs of 0.65 (0.45, 0.95; P = 0.02) and 0.42 (0.24, 0.71; P = 0.001), respectively. Six trials yielded a pooled mean difference (MD) of 8.08 (5.79, 10.37; P < 0.001) for BMD. In the HSPC we observed a stable improvement in increased BMD percentage with an MD (95%CI) of 6.65 (5.67, 7.62) (P = 0.001). CONCLUSIONS: ZA intervention does not significantly improve OS in patients with prostate cancer (HSPC, CRPC, M0, M1) but probably improves OS in the Asian populations. M1 and Asian groups had exhibit a significant reduction in SREs regardless of the HSPC or CRPC status after ZA administration. Moreover, ZA treatment increases BMD percentage.

Suprapubic Transvesical Repair of Vesicovaginal Fistula Using a Homemade Laparoscopic Single-Port Device: Experience of 42 Patients.

Aim: Vesicovaginal fistula (VVF) is the most common urogenital acquired fistula, and has remained a scourge and of public health importance. VVF can be repaired by transvaginal approach, transabdominal approach or transvesical approach, but the optimal management is still debated. Methods: To demonstrate a suprapubic transvesical approach to repair VVFs using a homemade laparoscopic single-port device. A retrospective review of the medical records of 42 consecutive patients who underwent fistula repair for VVF at our center from January 2012 to March 2018 was performed. VVFs were repaired by a suprapubic transvesical approach using a homemade laparoscopic single-port device. Clinical data, perioperative data and outcomes were collected. The primary outcome was VVF successful closure rate, and secondary outcome was perioperative complications. Results: The mean age of the patients was 44.6 (27-58) yr. The mean follow-up time was 65.6 (32-118) mo. The VVFs were successfully closed in 37 (88.1%) patients after the first surgery, and failure was observed in five patients. Initial failures of all the five patients were cured after a second repair. No major complication occurred as defined by Clavien-Dindo class 2 or greater. Conclusions: Suprapubic transvesical approach to repair VVFs using a homemade laparoscopic single-port device is a simple, effective, and feasible approach offering ideal results without major complications.

A Model for Identifying Optimal Patients for Primary Tumor Resection in Patients With Metastatic Bladder Cancer.

BACKGROUND: A survival benefit was observed in metastatic bladder cancer patients who underwent primary tumor resection, but it was still confusing which patients are suitable for the surgery. For this purpose, we developed a model to screen stage M1 patients who would benefit from primary tumor resection. METHODS: Patients with metastatic bladder cancer were screened from the Surveillance, Epidemiology, and End Results database (2004-2016) and then were divided into surgery (partial or complete cystectomy) group and non-surgery group. To balance the characteristics between them, a 1:1 propensity score matching analysis was applied. A hypothesis was proposed that the received primary tumor resection group has a more optimistic prognosis than the other group. The multivariable Cox model was used to explore the independent factors of survival time in two groups (beneficial and non-beneficial groups). Logistic regression was used to build a nomogram based on the significant predictive factors. Finally, a variety of methods are used to evaluate our model. RESULTS: A total of 7,965 patients with metastatic bladder cancer were included. And 3,314 patients met filtering standards, of which 545 (16.4%) received partial or complete cystectomy. Plots of the Kaplan-Meier and subgroup analyses confirmed our hypothesis. After propensity score matching analysis, a survival benefit was still observed that the surgery group has a longer median overall survival time (11.0 vs. 6.0 months, p < 0.001). Among the surgery cohort, 303 (65.8%) patients lived longer than 6 months (beneficial group). Differentiated characteristics included age, gender, TNM stage, histologic type, differentiation grade, and therapy, which were integrated as predictors to build a nomogram. The nomogram showed good discrimination in both training and validation cohorts (area under the receiver operating characteristic curve (AUC): 0.806 and 0.742, respectively), and the calibration curves demonstrated good consistency. Decision curve analysis showed that the nomogram was clinically useful. Compared with TNM staging, our model shows a better predictive value in identifying optimal patients for primary tumor resection. CONCLUSIONS: A practical predictive model was created and verified, which might be used to identify the optimal candidates for the partial or complete cystectomy group of the primary tumor among metastatic bladder cancer.

Macrophage correlates with immunophenotype and predicts anti-PD-L1 response of urothelial cancer.

Immune-checkpoint blockades (ICBs) have been routinely implemented to treat metastatic urothelial cancer (mUC), whereas robust biomarkers are urgently warranted. Herein, we explored latent promising biomarkers based on 348 pretreatment mUC samples from IMvigor210. Methods: The genome, transcriptome, immunome, and metabolome were systemically analyzed using the external TCGA dataset for validation. Kaplan-Meier and ROC curve analyses were performed to estimate the predictive capacity of M1-macrophage infiltration. Chi-square/Spearman/Mann Whitney U test are used to determine its correlation to genetic, biochemical, and clinicopathological parameters. Results: M1 frequency is a robust biomarker for predicting the prognosis and response to ICBs, which is non-inferior to tumor mutation burden (TMB) or tumor neoantigen burden (TNB), and exceeds CD8 T cells, T cell inflamed gene expression profile (GEP), and PD-L1 expression. Moreover, M1 infiltration is associated with immune phenotypes (AUC = 0.785) and is negatively correlated with immune exclusion. Additionally, transcriptomic analysis showed immune activation in the high-M1 subgroup, whereas it showed steroid and drug metabolism reprograming in the M1-deficient subset, which characterized the limited sensitivity to ICB therapy. Notably, investigation of the corresponding intrinsic genomic profiles highlighted the significance of TP53 and FGFR alterations. Conclusions: M1 infiltration is a robust biomarker for immunotherapeutic response and immunophenotype determination in an mUC setting. Innate immunity activation involving macrophage polarization remodeling and anti-FGFR mutations may be promising strategies for synergy with anti-PD-L1 treatments and may help prolong the clinical survival of patients with mUC.