Identify risk factors for perioperative outcomes in Intracorporeal Urinary Diversion and Extracorporeal Urinary Diversion with Robotic Cystectomy

ABSTRACT Introduction: The increasing adoption of robotic-assisted cystectomy with intracorporeal urinary diversion (ICUD), despite its complexity, prompts a detailed comparison with extracorporeal urinary diversion (ECUD). Our study at a single institution investigates perioperative outcomes and identifies risk factors impacting the success of these surgical approaches. Methods: In this retrospective analysis, 174 patients who underwent robotic-assisted cystectomy at the University of Louisville from June 2016 to August 2021 were reviewed. The cohort was divided into two groups based on the urinary diversion method: 30 patients underwent ECUD and 144 underwent ICUD. Data on demographics, complication rates, length of hospital stay, and readmission rates were meticulously collected and analyzed. Results: Operative times were comparable between the ICUD and ECUD groups. However, the ICUD group had a significantly lower intraoperative transfusion rate (0.5 vs. 1.0, p=0.02) and shorter hospital stay (7.8 vs. 12.3 days, p<0.001). Factors such as male sex, smoking history, diabetes mellitus, intravesical therapy, higher ASA, and ACCI scores were associated with increased Clavien-Dindo Grade 3 or higher complications. Age over 70 was the sole factor linked to a higher 90-day readmission rate, with no specific characteristics influencing the 30-day rate. Conclusion: Robotic cystectomy with ICUD results in shorter hospitalizations and lower intraoperative transfusion rates compared to ECUD, without differences in operative time, high-grade postoperative complications, or readmission rates. These findings can inform clinical decision-making, highlighting ICUD as a potentially more favorable option in appropriate settings.

Smoking characteristics and years since quitting smoking of US adults diagnosed with lung and bladder cancer: A national health and nutrition examination survey analysis

ABSTRACT Purpose: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. Materials and Methods: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. Results: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. Conclusions: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

Caracterización del cáncer vesical en adultos según variables clínicas y epidemiológicas / Characterization of bladder cancer in adults according to clinical and epidemiological variables

Introducción: El cáncer de la vejiga es uno de los más frecuentes del tracto urinario y se manifiesta de dos formas: como tumor superficial de bajo grado o como neoplasia invasora de alto grado. Objetivo: Caracterizar el cáncer vesical en adultos, según variables clínicas, epidemiológicas y de servicio. Métodos: Se realizó un estudio observacional descriptivo y retrospectivo, para caracterizar el cáncer vesical en adultos, según variables clínicas, epidemiológicas y de servicio de los pacientes atendidos en el servicio de Urología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro» en el periodo comprendido de octubre 2019 y 2022. Población del estudio: 242 pacientes diagnosticados con cáncer vesical. Resultados: La mayoría de los pacientes diagnosticados con cáncer vesical corresponden al año 2019 (45,86 %): masculinos (75,20 %); blancos (89,25 %); mayores de 70 o más años (64,46 %) y fumadores (95,45 %). La hematuria fue el síntoma principal (91,73 %), como expresión del carcinoma urotelial papilar de bajo grado (36,77 %). Tratamiento: la resección transuretral (88,01 %), sin metástasis a distancia (88,42 %). Conclusiones: La mayoría de los pacientes diagnosticados con cáncer vesical corresponden al año 2019, masculinos, blancos, mayores de 70 o más años, fumadores y con hematuria. Más frecuente: el carcinoma urotelial papilar de bajo grado. El tiempo trascurrido antes del diagnóstico de la enfermedad fue de 36-40 días, y un mes, el tiempo trascurrido antes del tratamiento de la enfermedad.

Introduction: bladder cancer is one of the most frequent cancers of the urinary tract and manifests itself in two ways: as a superficial low-grade tumor or as a high-grade invasive neoplasm. Objective: to characterize bladder cancer in adults according to clinical, epidemiological and service variables. Methods: a descriptive and retrospective observational study was carried out to characterize bladder cancer in adults according to clinical, epidemiological and service variables of patients treated in the Urology service at "Arnaldo Milián Castro" Clinical and Surgical University Hospital from October 2019 and 2022. The study population was 242 patients diagnosed with bladder cancer. Results: most of the patients diagnosed with bladder cancer correspond to the year 2019 (45.86%): male (75.20%); whites (89.25%); older than 70 or more years (64.46%) and smokers (95.45%). Hematuria was the main symptom (91.73%), as an expression of low-grade papillary urothelial carcinoma (36.77%). The treatment was transurethral resection (88.01%), without distant metastasis (88.42%). Conclusions: most of the patients diagnosed with bladder cancer correspond to the year 2019, male, whites, older than 70 years or older, smokers and with hematuria. Low-grade papillary urothelial carcinoma was the most frequent cancer. The time elapsed before the diagnosis of the disease was 36-40 days, and the time elapsed before the treatment of the disease was 1 month.

lncRNA ZFP36-AS1 regulates proliferation and immune escape of bladder cancer cell through miR-221 / 国际外科学杂志

Objective:To investigate the expression of long non-coding RNA(lncRNA) ZFP36-AS1 in bladder cancer and the effect of ZFP36-AS1/miR-221 axis on the proliferation and immune escape of bladder cancer cells.Methods:The expression difference of ZFP36-AS1 in bladder cancer tissues was analyzed by cBioPortal database. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression difference of ZFP36-AS1 in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637). MGH-U3 cells were randomly divided into negative control (NC) group and ZFP36-AS1 group, which were transfected with pcDNA3.1-NC plasmid and pcDNA3.1-ZFP36-AS1 plasmid, respectively. Colony formation assay and flow cytometry were used to analyze the proliferation activity and cell cycle of MGH-U3 cells, respectively. T lymphocytes were co-cultured with MGH-U3 cells in each group, and the levels of interleukin-10 (IL-10), γ-interferon (IFN-γ), and interleukin-4 (IL-4) in the supernatants of each group were detected by enzyme-linked immunosorbent assay (ELISA). The dual-luciferase reporter gene assay verified the targeting relationship between ZFP36-AS1 and miR-221. The effect of ZFP36-AS1 on the expression of miR-221 in MGH-U3 cells was detected by RT-qPCR. Western blotting was used to detect the effect of ZFP36-AS1/miR-221 axis on the protein expression of CDK3, Cyclin C, CDK5, Cyclin D1 and Cyclin D3 in MGH-U3 cells.Results:Compared with normal bladder tissue, ZFP36-AS1 was abnormally low-expressed in bladder cancer tissue ( P<0.01). Compared with SV-HUC-1 cells, ZFP36-AS1 was abnormally low-expressed in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637) ( P<0.01), and the expression was lowest in MGH-U3 cells ( P<0.01). The number of MGH-U3 cell colonies formed in the NC group and the ZFP36-AS1 group were (220.80±34.65) and (77.84±19.11), respectively, and the number of MGH-U3 cell colonies formed in the ZFP36-AS1 group was significantly down-regulated, the difference was statistically significant ( P<0.01). The proportions of G 0/G 1 phase cells in NC group and ZFP36-AS1 group were (48.04±2.89)% and (72.89±3.46)%, respectively, and the proportion of S phase cells were (35.38±2.98)% and (20.62±2.56)%, respectively. The proportion of G 2/M stage cells was (16.59±1.46)% and (6.48±1.50)%, respectively. The proportion of cells in G 0/G 1 phase were up-regulated in ZFP36-AS1 group ( P<0.01), and the proportion of cells in S phase and G 2/M phase were both down-regulated ( P<0.01). Compared with the NC group, the levels of IL-4 and IFN-γ in the ZFP36-AS1 group were significantly up-regulated ( P<0.01), and the level of IL-10 was significantly down-regulated ( P<0.01). ZFP36-AS1 can target miR-221 ( P<0.01). The relative expression of miR-221 in the NC group and the ZFP36-AS1 group was 6.84±1.35 and 1.00±0.21, respectively. Compared with the NC group, overexpression of ZFP36-AS1 could significantly inhibit the expression of miR-221 ( P<0.01). Compared with the NC group, the expressions of CDK3, Cyclin C, CDK5, Cyclin D1, and Cyclin D3 in the ZFP36-AS1 group were significantly decreased. Conclusion:ZFP36-AS1 is abnormally low-expressed in bladder cancer, and it reduces the proliferation activity of bladder cancer cells and inhibits their immune escape by inhibiting the expression of miR-221.

Primary large cell neuroendocrine carcinoma of bladder with urothelial carcinoma: a case report / 中华泌尿外科杂志

Large cell neuroendocrine carcinoma of bladder is a rare malignant tumor with high degree of malignancy, strong invasiveness and poor prognosis. We reported a case of a 56-year-old man who underwent transurethral resection of bladder tumor because of bladder mass. Postoperative pathology revealed large cell neuroendocrine carcinoma of the bladder with urothelial carcinoma. Radical cystectomy was performed after postoperative chemotherapy, and there was no recurrence after 3 months of follow-up.

Integrating the continuous-time random-walk diffusion model and the vesical imaging-reporting and data system to predict muscle invasion of bladder cancer / 中华放射学杂志

Objective:To investigate the diagnostic performance of continuous-time random-walk (CTRW) diffusion model combined with vesical imaging-reporting and data system (VI-RADS) in the diagnosis of muscle invasion of bladder cancer.Methods:In this case-control study, 64 patients with pathologically confirmed bladder urothelial carcinoma in Peking University First Hospital were retrospectively enrolled from August 2022 to March 2023. The patients were divided into the muscle invasive bladder cancer (MIBC) group and the nonmuscle invasive bladder cancer (NMIBC) group (29 cases and 35 cases, respectively) according to the pathological results. All patients underwent bladder MRI within 4 weeks before surgery, including T 2WI, conventional diffusion weighted imaging (DWI), and multi-b-value DWI. The CTRW model was used to obtain three quantitative diffusion parameters, including D m (an anomalous diffusion coefficient), α (related to temporal diffusion heterogeneity), and β (related to spatial diffusion heterogeneity). The apparent diffusion coefficient (ADC) was calculated using a mono-exponential model. The VI-RADS scores were evaluated based on T 2WI and conventional DWI. The Mann-Whitney U test was used to compare the diffusion parameters between the MIBC group and the NMIBC group. The combination of the parameters was investigated with logistic regression analysis. The diagnostic performance for muscle invasion of bladder cancer was evaluated by receiver operating characteristic analysis and the area under the curve (AUC). The difference between AUC was compared using the DeLong test. Results:There were statistically significant differences in ADC, D m, and α between the MIBC group and the NMIBC group ( Z=-2.31, -2.91, -3.97, P=0.021, 0.004,<0.001). No significant difference was found in β between the two groups ( Z=1.69, P=0.091). The AUC (95% CI) of D m and α for diagnosing MIBC were 0.712 (0.587-0.838) and 0.790 (0.676-0.904) respectively, both of which were higher than that of ADC (AUC 0.669, 95% CI 0.537-0.801) with statistically significant differences ( Z=2.86, 2.27, P=0.004, 0.023). The AUC (95% CI) of CTRW (D m+α) was 0.782 (0.661-0.876), which was significantly higher than that of ADC ( Z=2.35, P=0.019). The AUC (95% CI) of VI-RADS score and VI-RADS combined with CTRW parameter (VI-RADS+D m+α) were 0.823 (0.716-0.930) and 0.900 (0.799-0.961) respectively, with a statistically significant difference between them ( Z=2.16, P=0.031). Conclusion:The D m and α parameters in the CTRW diffusion model show better performance than the ADC in the mono-exponential model for muscle-invasive evaluation of bladder cancer, and the CTRW diffusion model can enhance the diagnostic performance of VI-RADS.

Factores de riesgo asociados al cáncer vesical en pacientes adultos / Risk factors associated with bladder cancer in adult patients

Introducción: El cáncer vesical es una enfermedad que afecta, generalmente, a pacientes masculinos de la tercera edad. Este tumor tiene dos formas principales de manifestarse: como tumor superficial y de bajo grado, o como neoplasia invasora de alto grado. La mayoría de los pacientes afectados con esta enfermedad presentan como factor de riesgo, el consumo de tabaco. Objetivo: Contribuir al conocimiento de la comunidad científica en lo relativo a los factores de riesgo y al síntoma principal asociados al cáncer vesical en pacientes adultos de la tercera edad. Métodos: Se realizó una revisión sistemática sobre el tema en las bases de datos: SciELO, EBSCO, Scopus, PubMed, y en revistas de Urología. Los artículos fueron publicados en idioma español o inglés. Se realizó un análisis del contenido para lograr la actualización teórica del tema. Conclusiones: El cáncer vesical es una enfermedad multifocal que provoca la aparición de varias neoformaciones dentro del epitelio transicional, en toda su extensión. La presencia de hematuria asintomática en los pacientes adultos fue la causa más común de consulta con el urólogo. Dentro de los factores de riesgo, el principal fue el consumo de tabaco.

Introduction: bladder cancer is a disease that generally affects elderly male patients. This tumour has two main forms of manifestation: as a low-grade superficial tumor or as a high-grade invasive neoplasm. Most of the patients affected with this disease have tobacco consumption as a risk factor. Objective: to contribute to the knowledge of the scientific community in relation to the risk factors associated with bladder cancer in elderly patients. Methods: a systematic review on the subject was carried out in SciELO, EBSCO, Scopus and PubMed databases as well as in Urology journals. Articles published in Spanish or English languages were taken into account. A content analysis was conducted to achieve a theoretical update on this topic. Conclusions: bladder cancer is a multifocal disease that causes the appearance of several neoformations within the transitional epithelium and throughout its entire length. The presence of asymptomatic hematuria in adult patients was the most common reason for consultation with the urologist. The main risk factor was tobacco consumption.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center

ABSTRACT Purpose To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. Materials and Methods Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. Results A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. Conclusion The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

Identification and validation of a novel prognostic model based on platinum resistance-related genes in bladder cancer

ABSTRACT Background: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increasingly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. Materials and Methods: Platinum resistance-related DEGs (differentially expressed genes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based chemotherapy. The potential mechanism was explored by enrichment analysis. Results: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high- and low-risk groups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. Conclusion: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy benefits and overall survival for BC patients. The model might assist in therapeutic decisions for bladder malignancy.

Comparison of single-course versus multiple course prophylactic intravesical instillation chemotherapy for bladder tumor recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis / 中华老年医学杂志

Objective:To examine whether multiple-course prophylactic intravesical instillation chemotherapy is superior to single-course chemotherapy in preventing bladder tumor recurrence after radical nephroureterectomy(RNU)for primary upper tract urothelial carcinoma(UTUC).Methods:A comprehensive literature search was performed using the PubMed, Wanfang Data and China National Knowledge Infrastructure and all publications before March 2021 about clinical trials comparing the effects of single-course and multiple-course prophylactic intravesical instillation chemotherapy after RNU for UTUC were retrieved.Analysis was performed using Stata/SE 12.0.Results:Seven trials included a total of 998 patients, with 473 participants receiving multiple-course and 525 receiving single-course intravesical instillation chemotherapy.Bladder cancer recurrence occurred in 69 out of 473 patients(14.6%)with multiple-course chemotherapy and in 123 out of 525 patients(23.4%)with single-course chemotherapy.The absolute risk reduction was 8.8% and the relative risk reduction was 37.6%.Compared with a single-course instillation, the pooled OR of bladder cancer recurrence was 0.55(95% CI: 0.40-0.76, P<0.001)for multiple-course instillations.No serious adverse events were reported. Conclusions:Compared with single-course instillation chemotherapy, multiple-course prophylactic intravesical instillation chemotherapy significantly decreases the risk of bladder cancer recurrence in primary UTUC patients treated with RNU, indicating multiple intravesical instillation chemotherapy is superior to single instillation chemotherapy.

The prognostic effect of pelvic lymph node dissection on the patients undergoing radical cystectomy / 中华泌尿外科杂志

Objective:To discuss the efficacy of pelvic lymph node dissection (PLND) on the patients undergoing radical cystectomy (RC).Methods:The clinicopathological data of bladder cancer patients who did not receive neoadjuvant chemotherapy and underwent RC in our center from November 2013 to December 2019 were collected. The average age of the patients was (67.4±10.9) years, including 284 males and 55 females. Postoperative pathology showed that 171 cases of MIBC and 168 cases of NMIBC. In the MIBC group, 124 patients received PLND. In the NMIBC group, 118 patients received PLND. There was no statistical difference of the PLND ratio between the two groups(72.5% vs. 65.5%, P=0.643). The average number of lymph nodes(LNs)in patients receiving PLND was(13.7±7.1). Explore the prognostic factors in NMIBC and MIBC respectively. The Kaplan-Meier method was used to analyze the effect of PLND on the prognosis of patients in MIBC and NMIBC group. Results:In MIBC group, 26 patients showed positive LNs, while 98 had negative LNs. 144 cases were high-grade urothelial carcinoma, and 47 cases received adjuvant treatment. In NMIBC group, 4 patients exhibited positive LNs, while 114 had negative LNs. 99 cases were high-grade urothelial carcinoma, and 15 cases received adjuvant treatment. After a median follow-up of 24(13, 43)months, Kaplan-Meier survival analysis showed that the 5-year overall survival(OS)of 395 patients was 63.6%. MIBC had a 5-year OS rate of 47.5%, while NMIBC had a rate of 79.1%. Univariate Cox regression showed that age≥65 years( HR=2.07, 95% CI 1.21-3.54, P=0.009), high tumor grade( HR=9.76, 95% CI 2.39-39.90, P<0.01), and positive lymph nodes( HR=2.47, 95% CI 1.27-4.78, P=0.008)were risk factors for the prognosis of MIBC.PLND ( HR=0.37, 95% CI 0.23-0.60, P<0.01) and adjuvant therapy ( HR=0.21, 95% CI 0.10-0.46, P<0.01) were protective factors of MIBC. However, the only risk factor of NMIBC was high tumor grade ( HR=6.66, 95% CI1.51-29.50, P=0.012). PLND had no effect on the prognosis of NMIBC patients following RC( HR=1.32, 95% CI 0.37-4.75, P=0.667). Multivariate COX regression analysis revealed that high tumor grade( HR=6.38, 95% CI 1.54-26.50, P=0.011) was independent risk factor of MIBC, PLND( HR=0.59, 95% CI 0.35-0.99, P=0.047), as well as adjuvant therapy ( HR=0.30, 95% CI 0.13-0.68, P=0.004) were independent protective factors of MIBC. Further analysis discovered that MIBC patients with negative LNs had a better prognosis than those with no PLND (62.4% vs. 16.1%, P<0.01)and positive LNs(62.4% vs.32.3%, P=0.005). However, there was no difference in prognosis between the negative LNs and no PLND group in NMIBC patients (81.3% vs. 66.6%, P=0.764). Conclusions:This study found that PLND was an independent predictive factor for MIBC patients receiving radical cystectomy.

The value of VI-RADS score in postoperative prognosis evaluation of bladder cancer patients / 中华泌尿外科杂志

Objective:To investigate the value of the vesical imaging reporting and data system score (VI-RADS) in the prognostic assessment of patients with bladder cancer.Methods:The data of 294 patients with pathologically confirmed bladder cancer in our department from February 2012 to September 2019 were retrospectively analyzed. Divide the patients into two groups based on the surgical method. In the transurethral resection of bladder tumor (TURBT) group, there were 121 cases, 102 males and 19 females; The average age of the patients was (66.7±12.3) years old, 52 cases <65 years old, 69 cases ≥65 years old, with VI-RADS <3 in 84 cases, VI-RADS ≥3 in 37 cases. In the radical cystectomy (RC) group, there were 173 cases, including 154 males and 19 females; The average age of the patients was (65.7±10.8) years, 77 cases <65 years old, 96 cases ≥65 years old, with VI-RADS <3 in 51 cases and VI-RADS ≥3 in 122 cases. The prognostic factors of TURBT group and RC group were analyzed, and the predictive value of VI-RADS score on overall survival (OS) and progression free survival (PFS) of bladder cancer patients after surgery was analyzed.Results:In this study, there were 294 cases with postoperative pathological diagnosis of urothelial carcinoma. The pathological staging was Ta stage in 104 cases (35.4%), T 1stage in 82 cases (27.9%), T 2 stage in 58 cases (19.7%), T 3 stage in 34 cases (11.6%), and T 4stage in 16 cases (5.4%). Pathological grading: 11 cases (3.7%) were low malignant potential, 77 cases (26.2%) were low grade, and 206 cases (70.1%) were high grade. There were 186 cases (63.3%) in the NMIBC group and 108 cases (36.7%) in the MIBC group. In the TURBT group, there were 114 cases (94.2%) in the NMIBC group and 7 cases (5.8%) in the MIBC group; In the RC group, there were 72 cases (41.6%) in the NMIBC group and 101 cases (58.4%) in the MIBC group. In the NMIBC group, the VI-RADS<3 and ≥3 were 128 cases (68.8%) and 58 cases (31.2%), respectively ( P<0.01); In the MIBC group, 101 cases (93.5%) had a VI-RADS <3 and 7 cases (6.5%) had a VI-RADS ≥ 3, respectively ( P<0.01). In the high grade of postoperative pathological group, 62 cases (30.1%) had a VI-RADS <3 and 144 cases (69.9%) had a VI-RADS ≥ 3, respectively ( P<0.01); In the non-high grade of postoperative pathological group, the VI-RADS <3 and ≥ 3 were 73 cases (83.0%) and 15 cases (17.0%), respectively ( P<0.01). The median OS survival for all patients in this study was 27.4 (16.6, 38.1)months and the median PFS survival was 24.7(14.0, 36.8) months. The results of univariate analysis showed that age ≥ 65 years old (OS: HR=6.09, P=0.001; PFS: HR=1.71, P=0.035), postoperative pathological diagnosis of tumor muscle infiltration (OS: HR=4.66, P<0.01; PFS: HR=2.24, P=0.001), postoperative high-grade tumor (OS: HR=4.26, P=0.008; PFS: HR=1.92, P=0.023), and VI-RADS score ≥ 3 (OS: HR=4.24, P=0.001; PFS: HR=2.21, P=0.002) were associated with poorer OS and PFS in patients. Multifactorial Cox model analysis revealed that a score of VI-RADS ≥3 was an independent risk factor for OS ( HR=3.41, P=0.012) and PFS ( HR=2.23, P=0.016). In the TURBT group, univariate analysis found that VI-RADS ≥3 ( HR=2.05, P=0.053) and high grade of postoperative pathology ( HR=2.77, P=0.005) were associated with poor PFS in patients, multifactorial Cox model analysis found only high grade of postoperative pathology ( HR=2.54, P=0.013) to be an independent risk factor for PFS. In the RC group, VI-RADS ≥3 ( HR=3.29, P=0.032) and age ≥65 years ( HR=5.37, P=0.001) were found to be independent risk factors for OS. The survival curve showed that the 5-year OS rates for groups with a VI-RADS ≥ 3 and <3 were 93.9% and 73.1%, respectively ( P<0.01), and the 5-year PFS rates for groups with a VI-RADS ≥ 3 and <3 were 76.5% and 53.0%, respectively ( P<0.01), with statistically significant differences. Conclusions:This study showed that VI-RADS ≥3 was an independent risk factor for prognosis in patients with bladder cancer and was more significant in patients receiving RC, but was not a significant predictor of prognosis in patients receiving TURBT.

Research progress of tumor associated macrophages in bladder cancer immunotherapy / 中华泌尿外科杂志

Bladder cancer is one of the most common malignant tumors of the urinary system. Although immunotherapy has been applied to bladder cancer for many years, it still cannot achieve satisfactory results. Tumor associated macrophages play an important role in the immunosuppressive tumor microenvironment of bladder cancer, and affect the effect of BCG and ICIs immunotherapy on bladder cancer. Due to the high plasticity of TAM, different phenotypes of TAM have opposite effects in bladder cancer immunotherapy, while the complex interactions between TAM and other immune cells severely affect the efficacy of bladder cancer immunotherapy. Inhibition of monocyte recruitment to the tumor and TAM depletion, blockade of the M2 phenotype or reprogramming to the M1 phenotype, activation of TAM, and genetically engineered macrophages are new immunotherapeutic strategies targeting TAM in bladder cancer.

The prognosis and complications differences between MIBC and NMIBC in the orthotopic ileal neobladder / 中华泌尿外科杂志

Objective:To compare the prognosis and complications of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) patients undergoing radical cystectomy (RC) followed by ileal neobladder.Methods:The clinical data of 103 patients who underwent orthotopic ileal neobladder in Jiangsu Province Hospital from April 2010 to October 2021 were retrospectively analyzed. There were 51 MIBC patients and 52 NMIBC patients. In the MIBC group, there were 49 males and 2 females, aged (58.1 ± 8.9) years, with American Society of Anesthesiologists (ASA) score of 1-2 in 48 cases and 3 in 3 cases. Open radical cystectomy (ORC) was performed in 2 cases, laparoscopic (LRC) in 34 cases and robot-assisted radical cystectomy (RARC) in 15 cases. In the NMIBC group, there were 49 males and 3 females, aged (55.7 ± 9.9) years, ASA score of 1-2 in 51 cases and ASA score of 3 in 1 case. LRC was performed in 41 cases, and RARC in 11 cases. There were no statistically differences between the two groups in above indicators ( P>0.05). The Clavien-Dindo grading system (CCS) was used to assess the complications, defining CCS Ⅰ-Ⅱ as mild complications and CCS Ⅲ-Ⅴ as severe complications. According to their relationship to the neobladder, complications were be classified as neobladder-related and non-neobladder-related complications. The occurrence of complications and the prognosis of neobladder between MIBC and NMIBC were compared. Results:The average operation time of the MIBC group and NMIBC group were (421.2 ± 119.7) min vs. (439.8 ± 106.2) min. The blood loss were 400 (300, 700) ml vs. 400 (300, 625) ml. The frequency of lymph nodes removed were (14.9 ± 8.3) vs. (14.8 ± 8.5). The postoperative defecation time were 5 (4, 6) d vs. 5 (3, 6) d. And the postoperative hospital stay were 20 (15, 28) d vs. 22 (19, 28) d. There were no statistically differences between the two groups in above indicators ( P>0.05). The MIBC group had a significantly lower rate of pelvic lymph node metastasis [17.6% (9/51) vs. 0(0/52), P=0.001] and tumor thrombosis [23.5% (12/51) vs. 5.8% (3/51), P=0.011] than the MIBC group. Moreover, the NMIBC group had a considerably superior 5-year overall survival (OS) (97.6% vs. 70.2%, P=0.035). The proportion of pads needed in the daytime of the MIBC group and NMIBC group were 14.6% (7/46) vs. 6.7% (3/45). The frequency of urination were (2.0 ± 0.7) h vs. (2.4 ± 0.7) h. Furthermore, The proportion of pads needed at night were 47.9% (23/48) vs. 53.3% (24/45). The frequency of nocturnal urination were 3.1±1.5 vs. 2.3 ± 1.7. And the number of pads needed at night were all 1 (0, 1) pad. The daytime and nighttime incontinence rate were 25.0% (12/48) and 62.5% (30/48) respectively in MIBC, compared to 11.1% (5/45) and 62.2% (28/45) respectively in NMIBC. And the proportion of erectile function retention were 15.8% (6/38) vs. 25.0% (10/40). There were no statistically significant differences in the prognosis of neobladder function between the two groups ( P>0.05). Furthermore, the proportions of mild complications in the MIBC group and NMIBC group were [41.2% (21/51) vs. 51.9 (27/52)]. The proportions of severe complications were [21.6% (11/51) vs. 19.2% (27/52)]. The proportions of neobladder-related complications were [27.5% (14/51) vs. 25.0% (13/52)]. And the proportions of non-neobladder-related complications were [39.2% (20/51) vs. 25.0% (13/52)]. There were no statistically significant differences in the complications between the two groups ( P>0.05). Conclusions:There was no statistically significant difference in functional prognosis and complications of neobladder between MIBC group and NMIBC group, and NMIBC had a better oncologic prognosis.

Advances in the diagnosis of bladder cancer based on Raman spectroscopy / 中华泌尿外科杂志

Bladder cancer is one of the common tumors of urinary system. Early detection and treatment can reduce the recurrence rate and mortality. Currently, it is difficult to balance the diagnostic specificity and sensitivity of traditional diagnostic methods. However, Raman spectroscopy, as a molecular diagnostic technology, can reveal the difference between normal urinary tract epithelial tissue and urinary tract epithelial cell carcinoma of the bladder at the molecular level, which has the characteristics of faster and more accurate diagnosis compared with traditional diagnostic techniques. This paper reviews the research progress of Raman spectroscopy in the diagnosis of bladder cancer.

Efficacy and safety of PD-1 inhibitors combined with chemotherapy versus chemotherapy alone in patients with metastatic bladder cancer / 中华泌尿外科杂志

Objective:To compare the efficacy and safety of programmed death-1(PD-1)inhibitors in combination with chemotherapy versus chemotherapy alone in patients with metastatic bladder cancer.Methods:A retrospective analysis was performed on the clinical data of 77 cases of metastatic bladder cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to October 2022. According to the different clinical treatment regimens, they were divided into two groups. Patients treated with PD-1 inhibitors combined with gemcitabine and cisplatin (GC) regimen were referred to as IGC group, and patients who received GC chemotherapy alone were referred to as GC group. There were 24 cases in IGC group, including 18 males and 6 females, with a median age of 60 (56, 67) years old. Seventeen cases had a history of smoking. Fifteen cases had an Eastern Cooperative Oncology Group (ECOG) score of 0 and 9 cases had a score of 1. Twenty-three cases suffered distant metastasis (stage M 1). Two cases suffered lymph node metastasis only, 6 cases with liver metastasis, 8 cases with lung metastasis, and 8 cases with bone metastasis. There were 53 cases in GC group, including 45 males and 8 females, with a median age of 63 (55, 69) years old. Thirty-one cases had a history of smoking. Thirty cases had an ECOG score of 0 and 23 cases had a score of 1, 48 cases suffered stage M 1, 2 cases suffered lymph node metastasis only. Nineteen cases suffered liver metastasis. Twenty-seven cases suffered lung metastasis. And 23 cases suffered bone metastasis. There was no statistically significant difference in the above general information between the two groups ( P>0.05). Kaplan-Meier method was used to plot the survival curves, and the difference of median progression-free survival (mPFS) and median overall survival (mOS) between the two groups was compared by log-rank test. Finally, the difference in adverse reactions between the two groups was compared. Results:The objective response rate (ORR) was 41.7% and the disease control rate (DCR) was 87.5% in the IGC group.As a comparison, the ORR was 43.4% and the DCR was 83.0% in the GC group. The differences in ORR ( P=0.887) and DCR ( P=0.871) between the two groups were not statistically significant. All patients were followed up for 3 to 45 months, with a median follow-up time of 24 (14, 43) months. The mPFS was 7.0 (95% CI 5.7-8.3) months in the GC group and 8.0 (95% CI 3.0-13.1) months in the IGC group, and the difference was statistically significant between the two groups ( P=0.026). The mOS of patients in the GC group was 16.0 (95% CI 14.4-17.6) months, the mOS was not yet reached in the IGC group, and patients in the IGC group had longer mOS with a statistically significant difference ( P=0.022). All patients experienced treatment-related adverse reactions. Grade 3-4 adverse reactions occurred in 8 cases (33.3%) in the IGC group and in 16 cases (30.2%) in the GC group, and no adverse reaction-related deaths were observed( P=0.992). The most common adverse reactions in both groups were anemia, including 18 cases (75.0%) in IGC group and 38 cases (71.7%) in GC group. There were 4 cases (16.7%) of grade 1-2 hypothyroidism in the IGC group but no patients with hypothyroidism were found in the GC group, and the difference was statistically significant ( P=0.012). There were 8 cases (33.3%) and 4 cases (7.5%) of grade 1-2 skin adverse reactions in the IGC and GC groups, respectively, and the difference was statistically significant ( P=0.011). The immune-related adverse reactions of PD-1 inhibitors in IGC group were 1 case of hyperthyroidism (4.2%), 4 cases of hypothyroidism (16.7%), 1 case of adrenal insufficiency (4.2%), and 1 case of immune colitis (4.2%). Conclusions:Compared with chemotherapy alone, PD-1 inhibitors combined with chemotherapy for metastatic bladder cancer can effectively prolong the mPFS and median mOS. The adverse reactions of the two groups were tolerable, and there was no significant difference in the incidence of grade 3-4 adverse reactions. In general, PD-1 inhibitors combined with chemotherapy in the treatment of metastatic bladder cancer is safe and feasible, but attention should be paid to the immune-related adverse reactions of PD-1 inhibitors.

Efficacy and safety of disitamab vedotin combined with tislelizumab in the neoadjuvant treatment of bladder cancer / 中华泌尿外科杂志

Objective:To evaluate the efficacy and safety of disitamab vedotin combined with tislelizumab in the neoadjuvant treatment of bladder cancer.Methods:The clinical data of 16 bladder cancer patients who received neoadjuvant therapy with disitamab vedotin combined with tislelizumab from April 2022 to January 2023 at the First Hospital of Chongqing Medical University were retrospectively analyzed. There were 15 males and 1 female, aged (66.12±14.37) years old. The immunohistochemical staining of biopsy pathology showed that HER-2 (0), (+ ), (+ + ), and (+ + + ) were in 1, 6, 6, and 3 cases, respectively. Before neoadjuvant therapy, 5 cases were in T 2N 0M 0 stage, and 11 cases were in T 3N 0M 0 stage. Biopsy pathology showed 3 cases were low-grade uroepithelial carcinoma, and 13 cases were high-grade uroepithelial carcinoma. Neoadjuvant therapy regimens: Disitamab vedotin 120 mg, every 2 weeks for 1 cycle, a total of 4 cycles. Tislelizumab 200 mg, every 3 weeks for 1 cycle, a total of 3 cycles. Surgery was performed at 2-3 weeks after neoadjuvant therapy. The efficacy and adverse effects of neoadjuvant therapy were analyzed. Results:All 16 cases completed neoadjuvant therapy.Five cases achieved complete remission, 7 cases achieved partial remission, 3 cases had stable disease, and 1 case had disease progression.Twelve cases(75.0%) achieved objective remission, 15 cases (93.8%) had disease control, and 14 cases(87.5%) had a reduction in the target lesion from baseline. Complete remission was achieved in 2 (22.2%)of 9 HER-2-positive patients and and 3 (42.9%) of 7 HER-2-negative patients, respectively, and objective remission was achieved in 8 (88.9%) and 4 (57.1%). After neoadjuvant treatments, surgical treatments were refused in 6 cases, and bladder-preserving combination therapy was performed in 2 cases. Radical cystectomy were performed in 8 cases, with negative margins for surgical incision, of which 5 cases (62.5%) had postoperative pathologic stage <T 2, and 2 cases (25.0%) reached pathological complete remission. Only 2 cases developed postoperative related complications, all of which improved with treatment. Grade 3-4 adverse reactions of neoadjuvant therapy included elevated blood glucose in 2 cases (12.5%), elevated ALT in 1 case (6.3%), hypertriglyceridemia in 1 case (6.3%), and leukopenia in 1 case (6.3%). Immune-related adverse reactions included rash in 3 cases (18.8%), hypothyroidism in 2 cases (12.5%), and immune colitis in 1 case (6.3%). Conclusions:In the neoadjuvant treatment of bladder cancer, disitamab vedotin combined with tislelizumab has high objective remission rate and disease control rate, low incidence of serious adverse reactions and high rate of negative surgical margins. It also has better efficacy in HER-2 negative patients.

The comparison of diagnostic accuracy between biparametric magnetic resonance imaging and multiparametric magnetic resonance imaging in muscle-invasive bladder cancer / 中华泌尿外科杂志

Objective:To compare the diagnostic accuracy between multiparametric magnetic resonance imaging (mp-MRI) and biparametric magnetic resonance imaging (bp-MRI) in muscle-invasive bladder cancer (MIBC).Methods:The clinical data of 195 patients with bladder cancer at the First Affiliated Hospital of Nanjing Medical University from July 2020 to June 2022, were retrospectively reviewed. There were 160 males and 35 females, with the median age of 68(61, 76)years old. Mp-MRI was performed on each patient within 6 weeks before transurethral resection of bladder tumor or radical cystectomy. Each patients’ images were divided into two sets. Set 1 (bp-MRI) included the axial, sagittal, coronal T2-weighted images (T2WI), and axial diffusion-weighted images (DWI) or apparent diffusion coefficient maps. Set 2 (mp-MRI) included Set 1 images in addition to dynamic contrast-enhanced images. All images were independently reviewed and evaluated by two radiologists. Mp-MRI was evaluated according to the Vesical Imaging-Reporting and Data System (VI-RADS)guideline, and bp-MRI was evaluated according to two types of criteria. Bp-MRI (Criterion A): VI-RADS scoring is determined 2 when T2WI 3-point with DWI 2-point. Bp-MRI (Criterion B): VI-RADS scoring is determined 3 when T2WI 3-point with DWI 2-point. VI-RADS scoring ≥ 3 or ≥ 4 was used as the cut-off value to predict MIBC. The sensitivity, specificity, positive predictive value, and negative predictive value of mp-MRI, bp-MRI (Criterion A), and bp-MRI (Criterion B) were calculated, as well as receiver operating characteristic curves and the areas under the curve (AUC).Results:Of 195 patients, 135 patients (69.2%) were pathologically confirmed as NMIBC and 60 patients (30.8%) were MIBC. When the VI-RADS cut-off value was ≥ 3, the sensitivity of mp-MRI, bp-MRI (Criterion A), and bp-MRI (Criterion B) were identical, all at 88.3% (53/60). The specificity of bp-MRI (Criterion A), bp-MRI (Criterion B), and mp-MRI were 88.9% (120/135), 73.3% (99/13), and 86.7% (117/135), respectively. When the VI-RADS cut-off value was ≥ 4, both bp-MRI (Criterion A) and bp-MRI (Criterion B) were classified as the same criterion. The sensitivity of bp-MRI and mp-MRI were 70.0% (42/60) and 75.0% (45/60), respectively. The specificity of bp-MRI and mp-MRI were identical, at 95.6% (129/135). The AUC for bp-MRI (Criterion A), bp-MRI (Criterion B), and mp-MRI were 0.927 (95% CI 0.881-0.959), 0.904 (95% CI 0.853-0.941), and 0.927 (95% CI 0.881-0.959), respectively. The AUC for bp-MRI (Criterion A) and mp-MRI were significantly higher than that of bp-MRI (Criterion B) ( P<0.001). There was no significant difference in AUC between bp-MRI (Criterion A) and mp-MRI ( P=0.939). Conclusions:Bp-MRI (Criterion A), VI-RADS scoring is determined 2 when T2WI 3-point with DWI 2-point, shows comparable diagnostic accuracy in predicting MIBC with mp-MRI. Compared to bp-MRI (Criterion B), the corresponding situation when VI-RADS scoring is determined 3, bp-MRI (Criterion A) may have better diagnostic accuracy than bp-MRI (Criterion B) in predicting MIBC.

Assessment and application of tumor regression grade after neoadjuvant chemotherapy in bladder cancer / 中华泌尿外科杂志

Objective:To verify the prognostic significance of the tumor regression grade (TRG) for muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC) after neoadjuvant chemotherapy.Methods:The data of 70 MIBC patients treated with gemcitabine combined with cisplatin neoadjuvant chemotherapy and RC in Sun Yat-sen University Cancer Center between July 2016 to November 2021 were retrospectively reviewed. There were 65 males and 5 females, with an average age(59.79±10.56)years old. The patients accepted transurethral resection of bladder tumor (TURBT) specimens before neoadjuvant chemotherapy. Clinicopathological characteristics of patients were recorded and TRG was assessed. TRG evaluation criteria: TRG 1 was defined as no cancer residue, TRG 2 was defined as the proportion of residual cancer area to tumor bed area <50%, and TRG 3 was defined as the proportion of residual cancer area to the area of the tumor bed ≥ 50%. Chi-square test or Fisher's exact test were used to compare the relationship between patients' clinicopathological characteristics and TRG. The relationship between post-neoadjuvant therapy tumor and node(ypTN)stage, and survival, including overall survival(OS)and recurrence-free survival (RFS) were analyzed by Kaplan-Meier analysis. The pathologically locally descending disease was defined as (ypT < T 2 and ypN=N 0) and pathologically locally advanced disease was defined as (ypT≥T 2 and/or ypN ≥N 1). Cox regression was used for univariate and multivariate analysis of OS and RFS. Results:Chi-square test or Fisher exact test analysis showed TRG was significantly associated with ypT stage ( P < 0.001), ypN stage ( P = 0.002), lympho-vascular invasion ( P<0.001) and variant histology ( P<0.001). The OS of patients with TRG 1, TRG 2 and TRG 3 were 20.5(10.3, 31.8), 17.0(11.0, 30.8)and 15.0(11.0, 26.0) months, respectively, and the difference was significantly different( P = 0.037). The RFS of patients with TRG 1, TRG 2 and TRG 3 were 15.0(8.3, 25.5), 15.0(8.0, 27.0)and 11.0(4.5, 25.5) months, respectively, and the difference was significantly different ( P=0.029). There were significant differences between patients with pathologically locally descending disease and locally advanced disease in OS [18.5(10.3, 30.8)vs.15.0(11.0, 27.3)months, P = 0.013] and RFS [14.0(8.0, 24.0)vs. 11.5(8.0, 26.8)months, P = 0.012]. Among patients with locally advanced pathology, the OS was 19.5(11.0, 32.5)months for patients with TRG ≤2, 13.5(10.8, 26.0)months for patients with TRG 3( P=0.140). The RFS was 12.0(8.0, 31.0)months for those patients with TRG ≤2 and 11.0(6.0, 26.0)months for those patients with TRG 3( P = 0.180). Cox univariate analyses showed that patients with TRG 3 were associated with decreased OS ( HR = 6.043, 95% CI 1.170-31.213, P = 0.032) and RFS ( HR = 6.354, 95% CI 1.231-31.802, P = 0.027). Conclusions:This study showed that TRG was correlated with OS and RFS among patients. The patients who had the higher TRG had the worse prognosis. It was confirmed that TRG predicted the prognosis of patients undergoing radical cystectomy after neoadjuvant chemotherapy. Therefore, TRG assessment is recommend in pathology report for patients who had radical cystectomy after neoadjuvant chemotherapy.

A case report of bladder cancer combined with cyst of the bladder wall / 中华泌尿外科杂志

Bladder wall cysts are clinically rare, and even rarer when occurring simultaneously with bladder cancer. In this paper, we reported a patient with bladder cancer combined with a bladder wall cyst, who was admitted due to the urinary frequency and gross hematuria. Preoperative ultrasound and CT examination revealed a tumor in the left and right anterior wall of the bladder respectively. The cystoscopy showed low-grade uroepithelial carcinoma of the left wall of the bladder and occupancy of the right anterior wall of the bladder. Transurethral plasma enucleation of bladder tumor and suprapubic small incision partial cystectomy was performed. Postoperative pathology confirmed high-grade uroepithelial carcinoma of the left wall of the bladder and cyst of the right wall. There was no recurrence or metastasis 15 months after surgery.