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Background: Enhancer of zeste homolog 2 (EZH2) is one of the major epigenetic modifiers involved in the transcriptional repression of target genes through trimethylation of H3K27 (lysine 27 residue of histone H3). Deregulated expression of both EZH2 and H3K27me3 has been implicated in the biological behavior and prognostic outcome of various malignancies. Aim: To assess the role of EZH2 and H3K27me3 in the carcinogenesis of urothelial carcinoma of urinary bladder. Materials and Methods: One hundred fifty consecutive urothelial carcinoma cases of urinary bladder (54.7% high-grade) were included in this study. Immunohistochemical analysis for EZH2 and H3K27me3 was performed on whole tissue sections. A multiplication score obtained by multiplying staining intensity and proportion of positively stained neoplastic cells was used for assessment. Results: EZH2 showed a significant correlation with the tumor grade and lamina propria invasion (p < 0.001). The cases with high EZH2 expression showed a significantly high proliferative index (Mean- 32.7%; p < 0.001). In contrast, negative and low expression of H3K27me3 was significantly more common in high-grade cases (p = 0.006). The expression of H3K27me3 was significantly associated with lamina propria (p = 0.01) and deep muscle invasion (p = 0.007). EZH2 showed a significantly higher expression in the high-grade invasive areas as compared to the high-grade non-invasive areas of the same tumor (p = 0.03). Conclusions: This study establishes an important role of the key epigenetic regulators EZH2 and H3K27me3 in the pathobiology of urothelial carcinomas. Strong expression of EZH2 and weak expression of H3K27me3 are associated with higher grade, proliferative index and invasive behavior.
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Fundamento: El cáncer primario de uretra se define como el tumor cuya primera lesión se localiza en la uretra; es infrecuente, el mismo representa menos del 1 % de los tumores malignos y el 5 % de los tumores malignos del sistema urinario. La extensión de este proceso a la glándula prostática genera sintomatología urinaria obstructiva e irritativa y cuadros agudos como la hematuria macroscópica. Objetivo: Presentar el caso de un paciente con cáncer primario de uretra en su variedad urotelial con hematuria macroscópica como forma clínica de presentación. Presentación del caso: Caso clínico de un paciente masculino de 75 años de edad, con hematuria macroscópica como forma clínica de presentación de cáncer primario de uretra en su variedad urotelial, el cual se diagnosticó anatomopatológicamente durante el estudio de la hematuria. Conclusiones: El caso que se presenta permite alertar a la comunidad científica que en pacientes que presentan hematuria macroscópica, sin manifestaciones urológicas obstructivas ni irritativas, también debe tenerse en cuenta el diagnóstico de cáncer uretral primario, aunque sea un signo infrecuente como forma clínica de presentación de esa enfermedad.
Background: Primary urethral cancer is defined as a tumor whose first lesion is located in the urethra; is very uncommon, represents less than 1% of malignant tumors and 5% of malignant tumors of the urinary system. The extension of this process to the prostate gland creates obstructive and irritative urinary symptoms and acute conditions such as macroscopic hematuria. Objective: To present the case of a patient with primary urethral carcinoma in its urothelial variety with macroscopic hematuria as clinical presentation. Case presentation: Clinical case of a 75-year-old male patient, with macroscopic hematuria as a clinical presentation of primary cancer of the urethra in its urothelial variety, diagnosed anatomopathologically during the hematuria study. Conclusions: The case presented alerts the scientific community that the diagnosis of primary urethral cancer should be considered in patients with macroscopic hematuria in the absence of obstructive or irritative urologic manifestations, although it is a rare sign as clinical presentation of this disease.
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Humans , Urethral Neoplasms , Urologic Neoplasms , HematuriaABSTRACT
Bladder cancer is one of the leading malignancies in the world associated with signi?cant morbidity and mortality. About 80% of a bladder cancer is urothelial variant, remaining 20% will have a divergent histological presentation. The pathophysiological study of these variants has recently increased because the therapeutic approach is not uniform for all variants. These variants have important diagnostic, prognostic and therapeutic implications. A molecular and genetic study of these variants will allow them to be better de?ned. Here we present four cases of Histological variants of bladder tumors with varying presentations in the department of urology, Madurai medical college, which is studied over the period of one year (2022-2023).
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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.
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Female , Humans , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , Leukocytes, Mononuclear , Carcinoma, Transitional Cell , Antagomirs , Cell Line, Tumor , Urinary Bladder Neoplasms , Cell Proliferation , Endometrial Neoplasms/genetics , Apoptosis/genetics , Cell Movement/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Ureteroscopy plays an important role in the diagnosis and treatment of upper tract urothelial carcinoma (UTUC). Conventional ureteroscopy (URS) can not only identify the location, appearance and size of a tumor, but also assess tumor grade by biopsy. The continued development of electronic flexible ureteroscopy and assistive technologies has led to further advances in the diagnosis of UTUC. Ureteroscopic laser ablation can be used to treat low grade malignancy, renal insufficiency, or isolated kidney. However, the use of URS may have potential risks such as delay of radical treatment, increased surgical difficulty, intraoperative or postoperative complications and intravesical recurrence. This article reviews the advantages and disadvantages of ureteroscopy in the diagnosis and treatment of UTUC.
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【Objective】 To investigate the efficacy and safety of single position transabdominal and extraperitoneal laparoscopic radical nephroureterectomy in the treatment of upper tract urothelial carcinoma (UTUC). 【Methods】 Clinical data of 31 UTUC cases treated in our hospital during Nov.2018 and Jun.2022 were retrospectively analyzed, including 11 tumors in the right side, and 20 in left side. There were 14 cases of renal pelvic carcinoma, 16 cases of ureter carcinoma, and 1 case of renal pelvic carcinoma plus ureter carcinoma. 【Results】 All surgeries were successfully performed without conversion to open surgery. The mean operation time was (81.45±19.80) min, and the estimated blood loss was (69.03±24.13) mL. No serious perioperative complications were observed. The average postoperative hospital stay was (6.13±2.44) d, and the median follow-up was 28 (3.0-49.0) months. At the last follow-up, 2 patients died, 3 had recurrence, but no contralateral recurrence was observed. 【Conclusion】 Single position transabdominal and extraperitoneal laparoscopic radical nephroureterectomy is safe, effective and feasible in the treatment of UTUC. It is worth clinical popularization.
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【Objective】 To explore the factors influencing the survival and prognosis of patients with bladder urothelial carcinoma (BUC) after surgical treatment, and to establish an artificial intelligence algorithm to predict the effects of different surgical regimens. 【Methods】 BUC patients treated with surgery during Jan.2007 and Jan.2019 in The Second Hospital of Dalian Medical University and Nanfang Hospital of Southern Medical University were enrolled. The complete clinical and follow-up data were collected. Deep neural network (DNN) was used to establish an artificial intelligence algorithm model. A prediction model of survival and prognosis was established, and the influencing factors of survival were explored and ranked by the artificial intelligence algorithm. 【Results】 A total of 832 patients were involved, including 438 (52.64%) treated in The Second Hospital of Dalian Medical University, and 394 (47.36%) treated in Nanfang Hospital of Southern Medical University. Of all cases, 579 (69.6%) were non-muscle invasive bladder cancer, and 253 (30.4%) were muscle invasive bladder cancer. Transurethral resection of bladder tumor was conducted in 539 (64.8%) cases, partial cystectomy in 66 (7.9%) cases, and total cystectomy in 227 (27.3%) cases. The data of patients treated in Second Hospital of Dalian Medical University were used for DNN modeling, and the data of patients treated in Nanfang Hospital of Southern Medical University were used for external verification after modeling. Finally, it was concluded that the factors affecting survival and prognosis were T stage, pathological grade, hypertension or cardiovascular and cerebrovascular disease, hemoglobin, blood calcium, smoking, albumin, lymphocytes, age, ratio of albumin/globulin, operation method, N stage, and creatinine clearance rate in descending order. The model could be used for preoperative prediction. 【Conclusion】 Through DNN modeling and external verification, the influencing factors of postoperative survival can be predicted for patients with bladder cancer, and the surgical effects can also be predicted before operation. The model can provide artificial intelligence algorithm support for the selection of surgical methods and postoperative follow-up plans.
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【Objective】 To investigate the effects of preoperative ureteroscopy (URS) on the intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). 【Methods】 The clinical data of 241 UTUC patients treated during May 2012 and Jan.2020 in the Second Hospital of Laozhou University were retrospectively analyzed. The patients were divided into URS before RNU group (URS group) and non-URS before RNU group (non-URS group). The cumulative IVR rate, progression-free survival (PFS) and overall survival (OS) after RNU were compared, and the survival curve was drawn. Cox proportional hazards models were used to assess risk factors affecting IVR. 【Results】 Of the 241 patients, 64 (26.6%) were included in the URS group and 177 (73.4%) in the non-URS group. In the URS group, 49 underwent biopsy and 15 did not. All patients were followed up for a median of 44 (3 to 122) months, with a median time to recurrence of 12 (3 to 56) months. IVR occurred in 18 patients (28.1%) in the URS group and 25 (14.1%) in the non-URS group. Kaplan-Meier survival analysis showed that the cumulative IVR rate was higher in the URS group than in the non-URS group (all P<0.05), regardless of whether patients had a history of bladder cancer (BC) or not, while PFS was lower in the URS group than in the non-URS group (P=0.007). Cox multivariate regression analysis showed that URS (P=0.031) and complicated renal pelvis tumor and ureteral tumor (P=0.004) were independent risk factors for IVR. 【Conclusion】 Preoperative URS increases the incidence of IVR in patients with UTUC, and routine preoperative use of URS is not recommended.
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【Objective】 To reduce the misdiagnosis rate by analyzing the clinical data of patients with primary upper tract urothelial carcinoma (UTUC) complicated with calculi. 【Methods】 Clinical data of 7 UTUC with calculi patients treated during Sep.2018 and Apr.2022 were retrospectively analyzed, including general data, time from visit to diagnosis, imaging data, urine exudation cytological results, surgical methods, pathological stages and follow-up data. 【Results】 The ratio of male to female was 3∶4, and the mean age was 66.4 (55-72) years. The initiate imaging examination results only showed calculi, but did not indicate suspicious tumor (including 1 case with missing data). The median time from the first visit to diagnosis was 12 months (5-36 months). Of all 7 cases, 2 (2/4) were clinically diagnosed by enhanced CT, 3 (3/4) by MRI, and 2 (2/7) by positive urine exudation cytology. All patients received surgical treatment. Postoperative pathology showed 85.71% (6/7) were high-grade UTUC. Postoperative staging was T1N0M0 in 4 cases, T3N0M0 in 2 cases, and T4N2M0 in 1 case. Adjuvant chemotherapy was conducted in 2 cases. During the median follow-up of 12 months (6-41), 1 case developed multiple systemic metastases in month 9, while the other cases had no recurrence or metastasis. 【Conclusion】 For UTUC patients without obvious filling defect on imaging, especially when ipsilateral calculi were complicated, misdiagnosis should be alerted for timely treatment and better prognosis.
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Urothelial carcinoma (UC) is the second most common genitourinary tumor, and upper tract urothelial carcinoma (UTUC) accounts for 5% to 10% of UC. Intravesical recurrence (IVR) occurs in 22% to 47% of patients after radical resection. This article reviews the mechanism, characteristics, related risk factors, regular bladder monitoring, diagnosis and treatment, and preventive measures of IVR, hoping to provide reference for clinical work.
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【Objective】 To investigate the predictive value of preoperative platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) (NLR-PLR) in peripheral blood for the prognosis of patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical surgery. 【Methods】 The clinical data of 104 UTUC patients who underwent radical nephroureterectomy plus bladder sleeve resection in our hospital during Jan.2015 and Dec.2020 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was drawn according to NLR and PLR, the optimal cut-off values of NLR and PLR were calculated, and NLR-PLR was determined accordingly. The patients were divided into NLR-PLR group 1 (PLR ≥161.46 and NLR≥ 2.51) and NLR-PLR group 0 (remaining patients). Chi-square test was used for comparison between groups, and the Kaplan-Meier method was used to draw survival curves. According to the Cox univariate and multivariate risk regression models, the risk factors for decreased overall survival (OS) were determined. 【Results】 The optimal cut-off values of PLR and NLR were 161.46 and 2.51, respectively. There were 74 patients in the NLR-PLR group 0 and 30 in the NLR-PLR group 1. Cox multivariate regression analysis showed that T stage, maximum tumor diameter and NLR-PLR were independent risk factors for reduced OS (P<0.05). 【Conclusion】 Preoperative NLR-PLR is a potential predictor of the prognosis of UTUC patients. Higher NLR-PLR is associated with poorer prognosis.
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【Objective】 To investigate the predictive value of preoperative controlled nutritional status (CONUT) score and ratio of hemoglobin to red cell distribution width (HRR) for survival of patients with upper urinary tract urothelial carcinoma (UTUC) after radical surgery. 【Methods】 A retrospective analysis was performed on 145 UTUC patients who underwent surgical treatment in the Affiliated Hospital of Xuzhou Medical University during May 2011 and Jun. 2017. Clinic opathologic data were collected, the best cut-off values of CONUT score and HRR were determined with receiver operating characteristic (ROC) curve, and the CONUT-HRR scoring system was established. The correlation between different CONUT-HRR scores and clinic opathological indicators of UTUC patients was compared. The application value of CONUT-HRR score in predicting the prognosis of UTUC patients was evaluated with Kaplan-Meier survival curve and Cox proportional risk regression model. 【Results】 The optimal cut-off values of preoperative CONUT score and HRR for predicting cancer specific survival (CSS) were 3 and 10.41, respectively. The patients were divided into three groups: CONUT-HRR 0 group (n=62, CONUT score <3 and HRR ≥10.41), CONUT-HRR 1 group (n=51, CONUT score <3 and HRR <10.41, or CONUT score ≥3 and HRR≥10.41), and CONUT-HRR 2 group (n=32, CONUT score ≥3 and HRR <10.41). CONUT-HRR score was correlated with age, surgical method, pathological T stage, lymph node metastasis and vascular invasion (all P<0.05). Kaplan-Meier survival curve results showed that the 5-year CSS of CONUT-HRR 0, 1 and 2 groups were 96.4%, 65.8% and 30.9%, respectively, with statistically significant differences (P<0.001). Cox regression model showed that CONUT-HRR score, pathological T stage, lymph node metastasis and vascular infiltration were independent factors of CSS. 【Conclusion】 Preoperative CONUT-HRR score can be used as a simple and reliable indicator to evaluate the prognosis of UTUC patients. Higher score indicates worse prognosis.
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【Objective】 To investigate the clinical characteristics,treatment and prognosis of primary urethral cancer (PUC). 【Methods】 The clinical data of 24 PUC patients treated in our hospital during Jan.2013 and Jul.2022 were retrospectively analyzed. The patients were followed up to monitor the metastasis,recurrence and survival. 【Results】 The patients included 17 male and 7 female,aged (57.6±12.8) years. The main pathologic type was squamous cell carcinoma,followed by urothelial carcinoma. Altogether 23 patients underwent surgical treatment,and 8 of them received postoperative radiotherapy or chemotherapy. During the follow-up of 1 to 92 months,17 patients were followed up,3 of the them had local recurrence,1 had metastasis,and 5 died. Survival analysis showed that patients survived (63.3±10.6) months,with a 21-month survival rate of 64.8% and progression-free survival of 22 (9,72) months. 【Conclusion】 PUC is a rare malignant tumor with poor prognosis. For early and distal PUC,urethra-preserving surgery can be adopted;for proximal or advanced PUC,surgery combined with radiotherapy or chemotherapy is recommended.
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ObjectiveTo investigate the feasibility of multiparametric MRI （mpMRI） combined with histogram analysis of apparent diffusion coefficient （ADC） in the assessment of patients with variant histology （VH） of urothelial carcinoma （UC）. MethodWe retrospectively analyzed the data of patients pathologically diagnosed with UC who underwent mpMRI in the First Affiliated Hospital of Sun Yat-sen University between March 2015 and March 2023. The patients were divided into VH group （urothelial carcinoma mixed with other histologies） and non-VH group （pure urothelial carcinoma） according to pathological results. We performed propensity score 1：1 nearest-neighbor matching on the two groups based on age and gender and 49 patients were included in each group. The regions of interest （ROIs） of the whole tumor were delineated manually by using ITK-SNAP software and Pyradiomics was applied to extract ADC histogram parameters. We compared the clinicopathological data， MRI morphological features and ADC histogram parameters between the groups. Multivariate logistic regression was used to identify independent risk factors and construct the prediction model. Receiver operating characteristic （ROC） curve analyses were performed to evaluate the diagnostic performance of these parameters for determining VH of UC. ResultsMRI morphological features including the lesion shape， vesical imaging-reporting and data system （Ⅵ-RADS）score， enhancement pattern and suspicious lymph node metastasis were markedly different between the two groups （all P < 0.05）. ADC mean， ADC median， ADC25th， ADC75th， ADC10th and ADC90th were significantly lower in patients with VH than those in non-VH group （all P<0.05）. Multivariate logistic regression analysis showed enhancement pattern， ADC25th， ADC75th and ADC mean were independent predictors （P < 0.05）. The combined model yielded the best predictive performance， with an area under the ROC curve （AUC） of 0.91 （95% CI： 0.83-0.96）. ConclusionsMpMRI combined with whole-tumor histogram analysis of ADC can serve as a reliable method for evaluating the presence of VH in UC， further to assist the clinical decision making.
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Objective:To explore the techniques and outcomes of pure laparoscopic native nephroureterectomy (LNUT) with ipsilateral allograft at a single position for upper tract urothelial carcinoma (UTUC) in renal transplant (RT) recipients.Methods:Clinical data were retrospectively reviewed for 12 renal transplant children undergoing native UTUC with ipsilateral allograft from January 2016 to December 2021.There were 4 boys and 8 girls.Complete LNUT was performed with bladder cuff resection at a single position via a transperitoneal approach.The interval between UTUC and RT was 12-146 months.There were 6 pelvic UCs and 6 ureter UCs.Results:All laparoscopic procedures were successfully completed without any serious perioperative complication.Postoperative pathological examination confirmed the diagnosis of urothelial carcinoma.And all surgical margins were negative.One patient experienced an elevation of creatinine after one cycle chemotherapy and normalized after withdrawing chemotherapy.The median follow-up period was (4-65) month.Two cases of contralateral native transitional cell carcinoma had radical nephroureterectomy two years later and another two cases underwent transurethral resection of bladder tumor one year later.One case died from tumor metastasis.The remainders had no tumor recurrence or metastasis during follow-ups.Conclusions:Complete single-position LNUT for UTUC with ipsilateral allograft is a safe and effective mini-invasive technique.Effectively avoiding the injury of allograft, it also offers the advantages of standard operation, minimal trauma, simple handling and enhanced recovery after surgery (ERAS).
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Objective:To explore the predictors of upper tract urothelial carcinoma (UTUC) invading muscle.Methods:The preoperative clinical data of 169 patients with UTUC who underwent radical nephroureterectomy (RNU) in the Department of Urology, Second Hospital of Tianjin Medical University from August 2019 to September 2021 were retrospectively collected. The average age of the patients was (67.7±8.3)years. There were 95 male cases (56.2%).15 cases (15.8%) were with diabetes, 46 cases (48.4%) with hypertension, 68 cases (71.6%) with hematuria, 44 cases (46.3%) with renal pelvis tumor, 74 cases (77.9%) with hydronephrosis and 8 cases (8.4%) with multifocality. There were 15 (20.3%), with diabetes, 40(54.1%) with hypertension, 58(78.4%)with hematuria, 32(43.2%) with renal pelvis tumor, 60(81.1%) with hydronephrosis and 2(2.7%) with multifocality among 74 female patients(43.8%), respectively. Patients’ body mass index (BMI) was (24.2±3.2) kg/m 2.The tumor diameter was (3.4±1.8) cm. The average count of neutrophil (NEU) was (4.2±1.7) ×10 9/L, with monocyte (MON) (0.4±0.2) ×10 9/L, platelet (PLT) (237.8±75.3) ×10 9/L and lymphocyte (LYM) (1.7±0.5) ×10 9/L. Neutrophil-to-lymphocyte ratio (NLR) was 2.7±1.4. Mmonocyte-to-lymphocyte ratio (MLR) was 0.3±0.1 and platelet-to-lymphocyte ratio (PLR) was 151.1±59.6. The concentrations of hemoglobin (Hb) and fibrinogen (FIB) were (127.1±18.3) g/L and(3.5±1.0) g/L. Univariate logistic regression analysis was performed on all preoperative data, and a nomogram was established to predict UTUC invading muscle by stepwise regression combined with multivariate logistic analysis. Concordance index (C-index) was used to evaluate the accuracy of the model, and Hosmer-Lemeshow test was used to check the fit. Using 1000 bootstrap resampling to validate the model and draw calibration plot. Receiver operating characteristics (ROC) curves were used to determine the most appropriate cut-off point of the model to predict tumor invasion and evaluate its sensitivity and specificity. Results:In this study, there were 169 cases. Postoperative pathological results showed that 18 cases (10.6%) were of low grade and 151 cases (89.4%) were of high grade. There were 2 patients (1.2%) with pT a stage, 44 patients (26.0%) with pT 1 stage, 37 patients (21.9%) with pT 2 stage, 81 patients (47.9%) with pT 3 stage and 5 patients (3.0%) with pT 4 stage. According to tumor stage, 46 patients were included into non-muscle invasive disease (NMID, pT a/T is/T 1) group and 123 patients were included into muscle invasive disease (MID, pT 2/T 3/T 4) group. Univariate analysis showed that hydronephrosis ( OR=2.919, 95% CI 1.332-6.387, P=0.007) was significantly correlated with MID. Tumor location in ureter ( OR=1.898, 95% CI 0.960-3.800, P=0.067), higher NLR value ( OR=1.313, 95% CI 0.9901.832, P=0.082) and FIB concentration ( OR=1.436, 95% CI 1.008-2.125, P=0.056) might have potential association with MID. Stepwise regression method was used to screen out PLT, FIB and hydronefrosis as the optimal combination for MID prediction. multivariate analysis suggested that PLT decreasing ( OR=0.727, 95% CI 0.548-0.955, P=0.023), FIB increasing ( OR=1.629, 95% CI 1.084-2.552, P=0.025) and hydronephrosis ( OR=2.500, 95% CI 1.111-5.601, P=0.026) were independent predictors of MID.The C-index of the model constructed by the three factors was 0.682, and the P-value of the goodness of fit was 0.778. The ROC curve showed that the optimal cut-off point for the prediction of high-risk MID by the nomogram was 0.627, achieving 39.1% specificity, 88.6% sensitivity and 0.682 area under the curve (AUC). Conclusions:Preoperative decrease of PLT, increase of FIB and hydronephrosis were independent factors for predicting UTUC invading muscle.
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The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) reported several advancements in the field of urothelial carcinoma. Multiple new treatment options for non-muscle invasive bladder cancer (NMIBC) were introduced, providing more choices for bladder preservation in BCG-resistant/failed NMIBC cases. In muscle invasive bladder cancer (MIBC) perioperative treatment, the updated 3-year follow-up data from the CheckMate 274 study demonstrated a clear advantage in disease-free survival for the nivolumab monotherapy adjuvant treatment group. For metastatic urothelial carcinoma (mUC), the final overall survival (OS) report from the IMvigor130 study was published, prompting further considerations for future first-line treatment options in mUC. Additionally, the conference highlighted research progress in upper tract urothelial carcinoma (UTUC).
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At present, antibody-drug conjugate is the focus of the research and development of new anticancer drugs. Three antibody-drug conjugates have been approved for the treatment of urothelial carcinoma, including Enfortumab Vedotin (Nectin-4 antibody-MMAE conjugate), Sacitumab Govitecan (Trop-2 antibody-SN-38 conjugate), and Disitamab Vedotin (HER2 antibody-MMAE conjugate) significantly improved the prognosis in patients with advanced disease, revolutionizing the treatment landscape of urothelial carcinoma. In addition, a number of studies that focus on combination of antibody-drug conjugate with targeted therapy, immunocheckpoint inhibitors is also under way. This article reviews the recent clinical development of antibody-drug conjugate in the treatment of urothelial carcinoma in recent years.
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Objective:To investigate the clinical features of diagnosis and treatment of renal parenchymal invasive urothelial carcinoma.Methods:The clinical data of 23 patients with renal parenchymal invasive urothelial carcinoma admitted to Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. There were 12 males and 11 females. The mean age was (67.3±10.1) years old. Among them, 7 cases complained of painless hematuria and 9 cases were asymptomatic. Three cases underwent preoperative MRI examination, 19 patients underwent preoperative enhanced CT examination, and 1 patient underwent both MRI and enhanced CT examination. MRI examination showed renal lobulated and other T1 mixed with T2 signals, the boundary was not clear, and DWI showed obvious restricted diffusion. The tumor was located on the left side in 15 cases and on the right side in 8 cases. Preoperative diagnosis was made by fine needle aspiration biopsy in 1 patient, and specimens were obtained by flexible ureteroscope in 2 patients. No tumor was reported. The preoperative diagnosis of 22 patients was unclear and the nature of the tumor could not be determined. One patient was considered to have urothelial carcinoma by fine needle aspiration. All patients were treated by surgery, including 20 cases of laparoscopic radical nephrectomy and 3 cases of nephroureterectomy with bladder sleeve resection.Results:Postoperative pathological specimens showed yellow-white mass, high-grade invasive urothelial carcinoma invading renal parenchyma. Nine cases were T 3a stage, 14 cases were T 3b stage, and 5 cases were lymph node metastasis. The average postoperative follow-up time was (18.6±6.72)months, 2 patients were lost to follow-up, 8 patients died, and the overall mortality rate was 38.1%. Seven patients died of recurrence or metastasis. There were 3 cases of bladder recurrence and 5 cases of metastasis after operation. Conclusions:Renal parenchymal infiltrating urothelial carcinoma is difficult to diagnose in the early stage, with poor clinical biological behavior and poor overall prognosis. For patients diagnosed with renal parenchymal invasive urothelial carcinoma preoperatively, laparoscopic nephroureterectomy + bladder sleeve resection is recommended.
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Introduction: High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC). Methods: We evaluated Ventana PD-L1 “SP263 and SP142” qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis. Results: SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node. Conclusion: PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.