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.

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.

Recidiva de los cánceres superficiales de vejiga posterior a quimioterapia intravesical con doxorrubicina / Recurrence of superficial bladder cancers after in-travesical chemotherapy with doxorubicin

Introducción: El cáncer de vejiga es una enfermedad de gran prevalencia, siendo su mayor problema la tendencia a la recidiva y a la progresión. Para disminuir en lo posible esta recidiva y progresión se han utilizado muchos quimioterapéuticos intravesicales aplicados a lo largo de meses tras la resección transuretral de vejiga con resultados desiguales. La doxorrubicina es un antibiótico antraciclino con actividad antitumoral producido por Streptococcus peucetius var. caesius. Tiene la capacidad de intercalarse con el DNA, afecta muchas de sus funciones e inhibe la síntesis de DNA y RNA, que por vía intravesical actúa evitando la implantación de células tumorales circulantes. Metodología: El estudio será de tipo observacional descriptivo, retrospectivo de corte transversal, comprendido entre el 1 de enero de 2018 y el 31 de enero de 2021 y desarrollado en el Servicio de Urología del Hospital Teodoro Maldonado Carbo. Resultados: Fueron 148 casos analizados. La especificidad del índice fue de 81 %, con un valor predictivo (VP) positivo del 77 % y VP negativo de 68 %. La sensibilidad de la ascitis 85 % y la masa abdominal palpable del 79 %. En las pacientes que presentaron valores de antígeno CA-125 menor a 1000 U/ml, el riesgo de obtener una citorreducción óptima fue OR: 0.15 (IC95% 0.069 ­ 0.307; P: 0.0001); las pacientes que presentaron valores del índice de irresecabilidad entre 1 y 2 puntos versus 3 y 4 fue de OR: 7.04 (IC95% 3.33 -14.87, P: 0.0001). Conclusiones: el cáncer de vejiga es una enfermedad prevalente que presenta desafíos significativos debido a su propensión a la recidiva y progresión. Para abordar este problema, se han utilizado diversos quimioterapéuticos intravesicales después de la resección transuretral de vejiga, aunque con resultados variables. La doxorrubicina, un antibiótico antraciclino con propiedades antitumorales, ha demostrado la capacidad de interferir con el ADN y el ARN, lo que la convierte en una opción valiosa para prevenir la implantación de células tumorales circulantes cuando se administra por vía intravesical.

Introduction: Bladder cancer is a highly prevalent disease; its most significant problem is its tendency to recur and progress. To reduce this recurrence and progression as much as possible, many intravesical chemotherapeutics applied over months after transurethral resection of the bladder have been used with mixed results. Doxorubicin is an anthracycline antibiotic with antitumor activity produced by Streptococcus peucetius var. cesius. It can intercalate with DNA, affects many of its functions, and inhibits the synthesis of DNA and RNA, which acts intravesically to prevent the implantation of circulating tumor cells. Methodology: The study will be of an observational, descriptive, retrospective, cross-sectional type between January 1, 2018, and January 31, 2021, and developed in the Urology Service of the Teodoro Maldonado Carbo Hospital. Results: A total of 148 cases were analyzed. The specificity of the index was 81%, with a positive predictive value (PV) of 77% and a negative PV of 68%. The sensitivity of ascites was 85%, and that of the palpable abdominal mass was 79%. In patients who presented CA-125 antigen values less than 1000 U/ml, the risk of obtaining optimal cytoreduction was OR: 0.15 (95% CI 0.069 - 0.307; P: 0.0001). The patients who presented unresectability index values between 1 and 2 points versus 3 and 4 points were OR: 7.04 (95% CI 3.33 -14.87, P: 0.0001). Conclusions: Bladder cancer is a prevalent disease that presents significant challenges due to its propensity for recurrence and progression. To address this problem, various intravesical chemotherapeutics have been used after transurethral resection of the bladder, although with variable results. Doxorubicin, an anthracycline antibiotic with antitumor properties, has demonstrated the ability to interfere with DNA and RNA, making it a valuable option to prevent the implantation of circulating tumor cells when administered intravesically.

Safe duration of silicon catheter replacement in urological patients

Objectives: This study compared the infection rates, degree of encrustation, symptoms, and complications in patients regarding the duration of urethral catheterisation (three weeks, six weeks, and eight weeks). Design: A cross-sectional study with stratified simple random sampling Setting: Urology Unit, Korle Bu Teaching Hospital Participants: One hundred and thirty-seven male patients with long-term urinary catheters Interventions: Participants were grouped into 3 weeks, 6 weeks, and 8 weeks duration of catheter replacementsPrimary outcomes measures: Symptoms due to the urinary catheters, urinalysis, urine and catheter tip cultures, sensitivity, and catheter encrustations were assessed. Results: Eighty-six patients had a primary diagnosis of benign prostatic hyperplasia (BPH), 35 had urethral strictures,13 had prostate cancer, two had BPH and urethral strictures, and one participant had bladder cancer. There was no difference in the symptoms the participants in the different groups experienced due to the urinary catheters (p > 0.05). The frequency of occurrence of complications (pyuria, p = 0.784; blocked catheter, p=0.097; urethral bleeding, p=0.148; epididymo-orchitis, p=0.769 and bladder spasms, p=1.000) showed no differences in the three groups. There was no statistical difference in the urinalysis for the three groups (p>0.05) and the degree of encrustations (3 weeks: 0.03 ± 0.06, 6 weeks: 0.11±0.27 and eight weeks: 0.12 ±0.27) with p=0.065. Conclusions: In this study, the duration of urinary catheterisation using silicone Foley's catheters did not influence the complication and symptom rates; hence silicon catheters can be placed in situ for up to 8 weeks before replacement instead of the traditional three-weekly change.

Research Progress in Preoperative Evaluation of Lymph Node Metastasis of Bladder Cancer / 中国医学科学院学报

Bladder cancer is a common malignant tumor of the urinary system.The prognosis of patients with positive lymph nodes is worse than that of patients with negative lymph nodes.An accurate assessment of preoperative lymph node statushelps to make treatmentdecisions,such as the extent of pelvic lymphadenectomy and the use of neoadjuvant chemotherapy.Imaging examination and pathological examination are the primary methods used to assess the lymph node status of bladder cancer patients before surgery.However,these methods have low sensitivity and may lead to inaccuate staging of patients.We reviewed the research progress and made an outlook on the application of clinical diagnosis,imaging techniques,radiomics,and genomics in the preoperative evaluation of lymph node metastasis in bladder cancer patients at different stages.

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Comparison of the survival outcomes between primary and secondary muscle-invasive bladder cancer: a propensity score-matched study / 中华医学杂志(英文版)

BACKGROUND@#Studies have classified muscle-invasive bladder cancer (MIBC) into primary (initially muscle-invasive, PMIBC) and secondary subtypes (initially non-muscle-invasive but progresses, SMIBC), for which controversial survival outcomes were demonstrated. This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.@*METHODS@#Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included. Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics. Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes. Propensity score matching (PSM) was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.@*RESULTS@#A total of 405 MIBC patients were enrolled, including 286 PMIBC and 119 SMIBC, with a mean follow-up of 27.54 and 53.30 months, respectively. The SMIBC group had a higher proportion of older patients (17.65% [21/119] vs. 9.09% [26/286]), chronic disease (32.77% [39/119] vs . 22.38% [64/286]), and neoadjuvant chemotherapy (19.33% [23/119] vs . 8.04% [23/286]). Before matching, SMIBC had a lower risk of overall mortality (OM) (hazard ratios [HR] 0.60, 95% confidence interval [CI] 0.41-0.85, P  = 0.005) and cancer-specific mortality (CSM) (HR 0.64, 95% CI 0.44-0.94, P  = 0.022) after the initial diagnosis. However, higher risks of OM (HR 1.47, 95% CI 1.02-2.10, P  = 0.038) and CSM (HR 1.58, 95% CI 1.09-2.29, P  = 0.016) were observed for SMIBC once it became muscle-invasive. After PSM, the baseline characteristics of 146 patients (73 for each group) were well matched, and SMIBC was confirmed to have an increased CSM risk (HR 1.83, 95% CI 1.09-3.06, P  = 0.021) than PMIBC after muscle invasion.@*CONCLUSIONS@#Compared with PMIBC, SMIBC had worse survival outcomes once it became muscle-invasive. Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.

Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma / 中华病理学杂志

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis / 中华肿瘤杂志

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Effects of lncRNA-UCA1 targeting miR-204-5p on the proliferation, migration, apoptosis and immune escape of endometrial carcinoma cells / 中华肿瘤杂志

Objective: To investigate the effect of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) gene on the proliferation, migration, apoptosis and immune escape of endometrial cancer cells and its molecular mechanism. Methods: Endometrial cancer tissues and adjacent normal tissues of patients with endometrioid adenocarcinoma who underwent total or partial hysterectomy in Henan Provincial People's Hospital from 2017 to 2019 were collected. The expressions of UCA1 and miR-204-5p were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the cell proliferation, migration and apoptosis were detected by cell counting kit 8 (CCK8) method, Transwell method, flow cytometry, and dual-luciferase reporter assay was used to explore the target relationship between UCA1 and miR-204-5p. HEC-1A-sh-NC or HEC-1A-sh-UCA1 cells were co-cultured with peripheral blood mononuclear cells (PBMC) or cytokine-induced killer cells in vitro to explore the role of UCA1 in immune escape. Results: The expression level of UCA1 in endometrial cancer tissue (17.08±0.84) was higher than that in adjacent normal endometrial tissue (3.00±0.37), and the expression level of miR-204-5p (0.98±0.16) was lower than that in adjacent normal endometrial tissue (2.00±0.20, P<0.05). Pearson correlation analysis showed that the expression of miR-204-5p was negatively correlated with the expression of UCA1 (r=-0.330, P=0.030). The expressions of UCA1 and miR-204-5p were associated with the International Federation of Gynecology and Obstetrics stage of endometrial cancer, lymph node metastasis and vascular invasion (P<0.05). The relative ratio of absorbance (0.58±0.11) and the number of cell migration [(199.68±18.44)] in the sh-UCA1 group were lower than those in the sh-NC group (1.24±0.17 and 374.76±24.83), respectively. The apoptosis rate of sh-UCA1 group [(28.64±7.80)%] was higher than that of sh-NC group [(14.27±4.38)%, P<0.05]. After different ratios of effector cells and target cells were cultured, the cell survival rate of HEC-1A-sh-UCA1 group was lower than that of HEC-1A-sh-NC group, and the difference was statistically significant (P<0.05). UCA1 had a binding site for miR-204-5p. The relative ratio of absorbance (1.74±0.08) and the number of cell migration (426.00±18.00) cells in the UCA1+ anti-miR-204-5p group were higher than those in the control group [1.00±0.03 and (284.00±8.00) cells, respectively]. The apoptosis rate of UCA1+ anti-miR-204-5p group [(5.42±0.93)%] was lower than that of control group [(14.82±1.48)%, P<0.05]. HEC-1A-sh-UCA1 cells could induce higher interferon gamma (IFN-γ) expression when co-cultured with PBMC, and the levels of IFN-γ expression in PHA group and PHA+ pre-miR-204-5p group cells were 2.42±0.49 and 1.88±0.26, which were higher than that in the PHA+ pre-NC group (0.85±0.10, P<0.05). When co-cultured with cytokine-induced killer cells (different ratios) in vitro, the HEC-1A-sh-UCA1 group and the HEC-1A-pre-miR-204-5p group had lower survival rates than that in the HEC-1A-pre-miR-204-5p group. In the HEC-1A-pre-NC group, the differences were statistically significant (P<0.05). Conclusion: UCA1/miR-204-5p may play an important role in human endometrial cancer.

Robot-assisted laparoscopic enucleation in the treatment of leiomyosarcoma of urinary bladder: A case report / 中南大学学报(医学版)

Leiomyosarcoma of urinary bladder (LMS-UB) is a highly malignant mesenchymal tumor, accounting for less than 0.5% of all bladder malignancies, with a predominant clinical presentation of hematuria. Here we report a case of low-grade LMS-UB. A 44-year-old male patient was admitted to the hospital with urodynia for 2 weeks. The patient's pelvis CT showed a mass on the right part of the bladder. For this reason, he was initially diagnosed with bladder cancer. We performed a robot-assisted laparoscopic enucleation of the bladder tumor and low-grade LMS-UB was diagnosed with the histopathological examination. He underwent 5 cycles of adjuvant chemotherapy after surgery. At 19months postoperative follow-up, the patient had no symptoms, recurrence, or distant metastasis. There is no report on the treatment of LMS-UB with minimally invasive enucleation worldwide. This case provides a new comprehensive treatment method of enucleation combined with adjuvant chemotherapy for early low-grade LMS-UB to reduce complications and improve patients' quality of life after surgery.

Construction of prognostic risk model of bladder cancer based on cuproptosis-related long non-coding RNAs / 浙江大学学报·医学版

OBJECTIVES@#To construct a prognosis risk model based on long noncoding RNAs (lncRNAs) related to cuproptosis and to evaluate its application in assessing prognosis risk of bladder cancer patients.@*METHODS@#RNA sequence data and clinical data of bladder cancer patients were downloaded from the Cancer Genome Atlas database. The correlation between lncRNAs related to cuproptosis and bladder cancer prognosis was analyzed with Pearson correlation analysis, univariate Cox regression, Lasso regression, and multivariate Cox regression. Then a cuproptosis-related lncRNA prognostic risk scoring equation was constructed. Patients were divided into high-risk and low-risk groups based on the median risk score, and the immune cell abundance between the two groups were compared. The accuracy of the risk scoring equation was evaluated using Kaplan-Meier survival curves, and the application of the risk scoring equation in predicting 1, 3 and 5-year survival rates was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression were used to screen for prognostic factors related to bladder cancer patients, and a prognostic risk assessment nomogram was constructed, the accuracy of which was evaluated with calibration curves.@*RESULTS@#A prognostic risk scoring equation for bladder cancer patients was constructed based on nine cuproptosis-related lncRNAs. Immune infiltration analysis showed that the abundances of M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells and neutrophils in the high-risk group were significantly higher than those in the low-risk group, while the abundances of CD8+ T cells, helper T cells, regulatory T cells and plasma cells in the low-risk group were significantly higher than those in the high-risk group (all P<0.05). Kaplan-Meier survival curve analysis showed that the total survival and progression-free survival of the low-risk group were longer than those of the high-risk group (both P<0.01). Univariate and multivariate Cox analysis showed that the risk score, age and tumor stage were independent factors for patient prognosis. The ROC curve analysis showed that the area under the curve (AUC) of the risk score in predicting 1, 3 and 5-year survival was 0.716, 0.697 and 0.717, respectively. When combined with age and tumor stage, the AUC for predicting 1-year prognosis increased to 0.725. The prognostic risk assessment nomogram for bladder cancer patients constructed based on patient age, tumor stage, and risk score had a prediction value that was consistent with the actual value.@*CONCLUSIONS@#A bladder cancer patient prognosis risk assessment model based on cuproptosis-related lncRNA has been successfully constructed in this study. The model can predict the prognosis of bladder cancer patients and their immune infiltration status, which may also provide a reference for tumor immunotherapy.

Manejo del cáncer de vejiga invasor de músculo con enfoque preservador de órgano: terapia trimodal / Management of muscle-invasive bladder cancer with an organ-sparing approach: trimodal therapy

El cáncer de vejiga es una patología frecuente del tracto genitourinario, cuyo tratamiento acarrea morbilidad y alteración de la calidad de vida y en particular en el subgrupo de pacientes con tumores vesicales clasificados como invasores de músculo. En los últimos años se han venido buscando alternativas terapéuticas para la cistectomía radical + linfadenectomía pélvica extendida, que es en la actualidad el estándar de manejo para los pacientes con carcinoma de vejiga invasor de músculo. Con el advenimiento de perfiles de manejo oncológico menos ablativos pero sin sacrificar resultados oncológicos y con las nuevas técnicas de radioterapia y quimioterapia, las modalidades terapéuticas preservadoras de órgano como la terapia trimodal (resección transuretral de tumor vesical + quimioterapia + radioterapia) se convierte en una alternativa terapéutica viable y con resultados oncológicos satisfactorios a largo plazo. Objetivo y metodología: Con esta revisión se pretende mostrar la actualidad de la terapia trimodal en el manejo de los tumores vesicales con invasión muscular, definir los mejores pacientes a considerar para recibir esta terapia, exponer los resultados oncológicos comparados con el estándar de manejo y los resultados en calidad de vida. También se propone un algoritmo de manejo y se presentar las recomendaciones al respecto en guías de práctica clínica. Conclusiones: La terapia trimodal es una alternativa al estándar de manejo que conduce a resultados oncológicos aceptables y puede considerarse una opción de tratamiento en pacientes bien seleccionados.

Introduction: Bladder cancer is a frequent pathology of the genitourinary tract, whose treatment causes morbidity and impaired quality of life, particularly in the subgroup of patients with bladder tumors classified as muscle invaders. In recent years, therapeutic alternatives have been sought for radical cystectomy + extended pelvic lymphadenectomy, which is currently the standard of care for patients with muscle-invasive bladder carcinoma. With the advent of less ablative oncological management profiles but without sacrificing oncological results and with new radiotherapy and chemotherapy techniques, organ-sparing therapeutic modalities such as trimodal therapy (transurethral resection of bladder tumor + chemotherapy + radiotherapy) becomes a viable therapeutic alternative with satisfactory long-term oncological results. Objective and methodology: This review aims to show the current status of trimodal therapy in the management of muscle-invasive bladder tumors, define the best patients to consider for receiving this therapy, present the oncological results compared with the management standard and the results in quality of life. A management algorithm is also proposed and recommendations in this regard are presented in clinical practice guidelines. Conclusions: Trimodal therapy is an alternative to standard management that leads to acceptable oncological outcomes and can be considered a treatment option in well-selected patients.

Tabaquismo y tumores mayores de 2 centímetros son predictores de mortalidad en pacientes sometidos a nefro-ureterectomías por carcinoma de urotelio alto / Prognostic factors in patients with upper urinary tract urothelial carcinoma undergoing nephro-ureterectomy

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) represents 5-10% of urothelial carcinomas. It is managed with nephroureterectomy (NUR); however, kidney-sparing techniques are growingly used. AIM: To report the results of a 20-year series of NUR conducted in an academic center. Patients and Methods: Review of clinical and pathological characteristics of patients undergoing NUR between 1999 and 2020. Patients were followed for 63 months. Global survival curves (OS) and mortality predictors were established through Cox regression. RESULTS: We included 90 patients with a median age of 68 years undergoing NUR, of whom 68 (75%) had a pelvic tumor and 22 (25%) had a proximal ureteral tumor. A laparoscopic NUR was performed in 60 patients (66%). Thirty-three patients (37%) had tumors confined to the urothelium (pTa), penetrating the lamina propria (pT1) or carcinoma in situ (CIS), 10 patients (11%) had a tumor spreading to the muscle layer (pT2) and 47 (52%) had a tumor spreading to nearby organs (pT3 / T4). Average tumor size was 3.69 cm, nodal disease (pN) was present 12 patients (13%). Twelve patients (13%) received adjuvant chemotherapy. A higher mortality was observed among smokers (Hazard ratio (HR) 8.79, 95% confidence intervals (CI) 1.5-49.0, p = 0.01), patients with tumors classfied as pT≥ 2 (HR 1.09, 95% CI 0.01-1.0, p = 0.04) and those with tumors larger than 2 cm (HR 14.79, CI 95% 1.5-272, p = 0.01). CONCLUSIONS: Smoking patients, those with invasive tumors (T2-T4) and greater than 2 cm have higher mortality. Therefore, they should not be candidates for conservative management.

Bricker ileal conduit vs. Cutaneous ureterostomy after radical cystectomy for bladder cancer: a systematic review

ABSTRACT Purpose: A systematic review of the literature with available published literature to compare ileal conduit (IC) and cutaneous ureterostomy (CU) urinary diversions (UD) in terms of perioperative, functional, and oncological outcomes of high-risk elderly patients treated with radical cystectomy (RC). Protocol Registration: PROSPERO ID CRD42020168851. Materials and Methods: A systematic review, according to the PRISMA Statement, was performed. Search through the Medline, Embase, Scopus, Scielo, Lilacs, and Cochrane Database until July 2020. Results: The literature search yielded 2,883 citations and were selected eight studies, including 1096 patients. A total of 707 patients underwent IC and 389 CU. Surgical procedures and outcomes, complications, mortality, and quality of life were analyzed. Conclusions: CU seems to be a safe alternative for the elderly and more frail patients. It is associated with faster surgery, less blood loss, lower transfusion rates, a lower necessity of intensive care, and shorter hospital stay. According to most studies, complications are less frequent after CU, even though mortality rates are similar. Studies with long-term follow up are awaited.

Computed-tomography based scoring system predicts outcome for clinical lymph node-positive patients undergoing radical cystectomy

ABSTRACT Purpose: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. Materials and Methods: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. Results: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p <0.001). Conclusion: In our study, solely LN size >15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation / 中国天然药物

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

MiR-133b regulates the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4 / 中南大学学报(医学版)

OBJECTIVES@#Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells.@*METHODS@#The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay.@*RESULTS@#Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells.@*CONCLUSIONS@#The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo / 中国结合医学杂志

OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.