High-grade Urothelial Carcinoma Research Articles

Primary high-grade urothelial carcinoma of prostate with prostatic hyperplasia: a rare case report and review of the literature

Background Primary urothelial carcinoma in the prostate (UCP) is extremely rare and occurs most frequently in the bladder. There are only dozens of primary cases reported in the literature. Here, we describe a rare case of primary UCP and review the literature. Case presentation A 67-year-old widowed male, was referred to our hospital due to the frequency, and urgency of dysuria. Magnetic resonance imaging (MRI) examination revealed prostate size was about 57 mm × 50 mm × 54 mm, increased prostatic transitional zone, and surrounding of prostatic duct indicate bar isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 3); posterior of peripheral zone indicate patchy isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 5). Subsequently, the patient underwent a transrectal prostate biopsy. Histopathological and immunohistochemical (IHC) assessments showed prostatic high-grade urothelial carcinoma with benign prostatic hyperplasia. Finally, the patient underwent laparoscopic radical prostatectomy. Four months after surgery, CT plain and enhanced scan revealed thickening of the bladder wall. On further workup, cystoscopy revealed lymphoid follicular changes in the cut edge of the radical prostatectomy, and cystoscopic biopsies showed the malignant tumor. Conclusions Prostatic urothelial carcinoma should always be considered if the patient with severe lower urinary tract symptoms or hematuria, PSA, and digital rectal examination without abnormalities, without a personal history of urothelial cancer, but contrast-enhanced MRI showed the lesion located in the prostate. As of right now, radical surgical resections remain the most effective treatment. The effectiveness of neoadjuvant or adjuvant chemotherapy is still controversial.

Clinicopathologic features and prognostic significance of mixed (Low and high-grade) papillary urothelial carcinoma comparison with low and high-grade papillary urothelial carcinoma.

The World Health Organization/International Society of Urological Pathology (2022 WHO/ISUP) classification categorizes noninvasive carcinomas based on the highest grade observed in a pathology sample. According to this classification, a lesion is classified as mixed-grade (MG) if the highest-grade component comprises less than 5% high-grade (HG) carcinoma [14]. This study included 160 cases of low-grade papillary urothelial carcinoma (LGUC) and 160 cases of HG papillary urothelial carcinoma (HGUC), selected randomly. In addition, 160 consecutive and unselected cases of MG papillary urothelial carcinoma (MGUC) were obtained from all bladder transurethral resection specimens diagnosed with papillary urothelial carcinoma between January 2007 and January 2021. The results of the multivariate analysis showed that histologic grade, invasion of the lamina propria, and the presence of carcinoma in situ at presentation were independent prognostic parameters regarding recurrence-free survival (p = 0.002; hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.059-1.956, p = 0.02; and HR = 1.76, 95% CI = 1.159-2.684, p = 0.008, respectively). Histologic grade was the only independent prognostic parameter of disease-specific survival (DSS) (p < 0.001). Comparisons between non-muscle invasive (NMI) MGUC and NMI LGUC, as well as between NMI MGUC and NMI HGUC, revealed statistically significant differences in terms of DSS (HR = 0.07, 95% CI = 0.024-0.252,p< 0.001 and HR = 1.59, 95% CI = 1.023-2.460, p = 0.039, respectively). Our study findings demonstrate statistically significant differences regarding DSS between NMI MGUC and NMI HGUC, as well as between NMI MGUC and NMI LGUC. Therefore, we suggested that considering the presence of less than 5% MGUC as a separate category may be appropriate. However, it is important to validate our results in larger cohorts with longer follow-up periods to establish the clinical significance of MGUC and provide guidance for patient management.

Immunohistochemical Expression of Clustered Differentiation 10 (CD10) Across Various Grade &amp; Stage of Urinary BladderCarcinoma

Objective: To assess the Clustered Differentiation 10 (CD10) expression in Urothelial carcinoma and to ascertain how its expression relates to grade and stage. Method: Descriptive cross sectional research was carried out over a period of six months in Pathology Department on eighty five cases of bladder carcinoma from transurethral resection of bladder (TURBT) specimens diagnosed on Hematoxylin-eosin (H &amp; E) stained sections irrespective of patient's age and gender were included in the study. These were stained for CD10 by Immunohistochemical technique. Results: Sixty seven (78.8%) urothelial carcinomas showed positive CD10 staining while 18 cases (21.17%) demonstrated negative expression. In 67 positive cases, 42 high grade tumors had 2+ expression while 13 grade had 1+ staining .All low-grade tumors(12) displayed 1+ score. Sixteen tumorsin pT1, 21 tumorsin pT2 and 3 tumors in pT3 stage displayed 2+ score. Nineteen tumors in pT1 while 4 tumors in pT2 had 1+ score. Conclusion: Our findings indicate that CD10 expression is greater in high grade and invasive urothelial carcinomas and is associated with progression of bladder carcinomas.

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology.

βIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high-grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki-67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer-related molecules, TUBB3 was an independent predictor of progression-free survival and high-grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high-grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.

Are we on track for diagnosing high-grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria.

The Paris System for Reporting Urinary Cytology (TPS) has gained universal acceptance as the standard for reporting urine cytology requiring at least 5-10 malignant cells to diagnose high-grade urothelial carcinoma (HGUC) in lower and upper urinary tract specimens, respectively. These quantitation criteria are still subject to discussion, and this study specifically aims to validate the quantitation criterion of HGUC in lower urinary tract. The authors reviewed two cohorts of lower urinary tract cases. The first cohort consisted of 100 liquid-based ThinPrep slides with the diagnosis of HGUC having positive histology on concurrent or follow-up biopsies within 3months. The second cohort was 36 HGUC cases with negative histology on concurrent biopsies and within 3months. The number of high-grade cells (HGCs) meeting the TPS qualitative criteria were counted under the light microscope driven in a grid-like manner. The first 100 urine samples showed five cases (5.0%) with three HGCs, three cases (3.0%) had four HGCs, five cases (5.0%) showed five HGCs, and 25 cases (25.0%) had between 6-10 HGCs. The risk of high-grade malignancy (ROHM) in cases with five or more HGCs was 100%, whereas those with three HGCs was 60.0%. The second cohort of HGUC was considered "positive" despite a negative histology. This study confirms that quantitation is an essential key to diagnose HGUC. The current TPS criterion of a minimum of five malignant cells in lower tract is robust with a ROHM of 100%. Diagnosing HGUC with less than five HGCs runs the risk of lowering the ROHM.

Clinical utility of urinary comprehensive genomic profiling in diagnosing metachronous upper tract urothelial carcinoma: a case report

Introduction and aim of studyMetachronous upper tract urothelial carcinoma (UTUC) is a rare yet aggressive malignancy that is often multifocal and invasive at the time of diagnosis. Unfortunately, the rarity of metachronous UTUC results in a paucity of targeted data, as current literature and clinical management of this tumor is largely extrapolated from that of bladder cancer. Urinary comprehensive genomic profiling with the UroAmp assay identifies six general classes of tumor-mutations present in the urine and thus, may aid in detecting UTUC when the limitations of current tools impede definitive diagnosis. We describe the utility of urinary comprehensive genomic profiling in confirming the provider’s suspicion for metachronous UTUC and recommending radical nephroureterectomy.Patient caseA 68-year-old male with a history of recurrent carcinoma in situ (CIS) of the bladder presented to the urology clinic in 2022 for continued surveillance. Abnormal soft tissue thickening surrounding the proximal right ureter, revealed on computerized tomography urography, prompted further evaluation. Selective right upper tract cytology was indeterminate, and urinary comprehensive genomic profiling was ordered to adjudicate. No tumor was visualized on ureteroscopy however the cytologic brush biopsy of the renal pelvis and proximal ureter were positive for urothelial carcinoma (UC) and/or CIS. UroAmp testing identified genomic features associated with high-grade UC, risk of invasion, and a high genomic disease burden.ResultsThe patient underwent a right kidney and ureter nephroureterectomy in September 2022. Surgical pathology confirmed non-invasive multifocal urothelial CIS. A postoperative urinary comprehensive genomic profiling in February and May of 2023 detected no evidence of residual disease, consistent with complete resection of the tumor. The provider will continue intensive urinary comprehensive genomic profile monitoring coupled with conventional surveillance.ConclusionUrinary measurement of mutated UC genes correlate with disease burden, pathologic grade, and invasion risk and provide clinical utility when reliance on visual confirmation and cytology were not definitive or feasible.

Diagnosis of Low-Grade Urothelial Neoplasm in the Era of the Second Edition of the Paris System for Reporting Urinary Cytology.

The Paris System for Reporting Urinary Cytology (TPS) is considered the gold standard when it comes to diagnostic classifications of urine specimens. Its second edition brought some important changes, including the abolition of the diagnostic category of "low-grade urothelial neoplasm (LGUN)", acknowledging the inability of cytology to reliably discern low-grade urothelial lesions. In this retrospective study, we assessed the validity of this change, studying the cytological diagnoses of histologically diagnosed low-grade urothelial carcinomas during a three-year period. Moreover, we correlated the sum of the urinary cytology diagnoses of this period with the histological diagnoses, whenever available. Although all the cytological diagnoses of LGUN were concordant with the histological diagnoses, most low-grade urothelial carcinomas were misdiagnosed cytologically. Subsequently, the positive predictive value (PPV) of urinary cytology for the diagnosis of LGUN was 100%, while the sensitivity was only 21.7%. Following the cyto-histopathological correlation of the sum of the urinary cytology cases, the sensitivity of urinary cytology for the diagnosis of high-grade urothelial carcinoma (HGUC) was demonstrated to be 90.1%, the specificity 70.8%, the positive predictive value (PPV) 60.3%, the negative predictive value (NPV) 93.6% and the overall accuracy 77.2%, while for LGUN, the values were 21.7%, 97.2%, 87.5%, 58.6% and 61.9%, respectively. Risk of high-grade malignancy was 0% for the non-diagnostic (ND), 4.8% for the non-high-grade urothelial carcinoma (NHGUC), 33.3% for the atypical urothelial cells (AUCs), 65% for the suspicious for high-grade urothelial carcinoma (SHGUC), 100% for the HGUC and 12.5% for the LGUN diagnostic categories. This study validates the incorporation of the LGUN in the NHGUC diagnostic category in the second edition of TPS. Moreover, it proves the ability of urinary cytology to safely diagnose HGUC and stresses the pivotal role of its diagnosis.

Bladder Epicheck Test: A Novel Tool to Support Urothelial Carcinoma Diagnosis in Urine Samples.

Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.

Does Chemo-Radiotherapy Improve Survival Outcomes vs. Radiotherapy Alone for High-Grade cT1 Urothelial Carcinoma of the Bladder?

BackgroundNon-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. MethodsPatients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. ResultsA total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008). ConclusionFor patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies.

A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms.

Exophytic papillary urothelial neoplasms (EPUN) are difficult to diagnose pathologically and are well-known for their heterogeneous prognoses. Thus, searching for an objective and accurate diagnostic marker is of great clinical value in improving the outcomes of EPUN patients. PHH3 was reported to be expressed explicitly in the mitotic phase of the cell cycle, and recent studies have shown that PHH3 expression was associated with the differential diagnosis and prognosis of many tumors. However, its significance in EPUN remains unclear. This study aimed to determine the expression of PHH3 in different EPUN, compare its expression with cell-cycle related proteins Ki67 and P53, and analyze its significance in the differential diagnosis and prognostic value for high-grade papillary urothelial carcinoma (HGPUC), low-grade papillary urothelial carcinoma (LGPUC), papillary urothelial neoplasm of low malignant potential (PUNLMP) and urothelial papilloma (UP). We retrospectively analyzed the pathological diagnosis and clinical features of 26 HGPUC cases, 43 LGPUC cases, 21 PUNLMP cases and 11 UP cases. PHH3, Ki67 and P53 were detected by immunohistochemistry in 101 EPUN cases samples. The cut-off values of PHH3 mitosis count (PHMC), HE mitosis count (HEMC), Ki67 and P53 in the different EPUN were determined using the ROC curve. The distribution of counts in each group and its relationship with clinical parameters and prognosis of EPUN patients were also analyzed. The determination coefficient (R2=0.9980) of PHMC were more potent than those of HEMC (R2=0.9734) in the EPUN mitotic counts microscopically by both pathologists. Of the 101 EPUN cases investigated, significant positive linear correlations were found between PHMC and HEMC, PHMC and Ki67, and HEMC and Ki67 (P<0.0001). In HGPUC, LGPUC, PUNLMP and UP, a decreasing trend was observed in the median and range of PHMC/10HPFs, HEMC/10HPFs, Ki67 (%) and P53 (%). PHMC, HEMC, Ki67 and P53 were associated with different clinical parameters of EPUN. PHMC, HEMC, Ki67 and P53 were found to exhibit substantial diagnostic values among different EPUN and tumor recurrence. Based on the ROC curve, when PHMC was >48.5/10HPFs, a diagnosis of HGPUC was more likely, and when PHMC was >13.5/10HPFs, LGPUC was more likely. In addition, when PHMC was >5.5/10HPFs, the possibility of non-infiltrating LGPUC was greater. Kaplan-Meier survival curve analysis showed that the median recurrence-free survival (RFS) for cases with PHMC > 13.5/10HPFs and HEMC > 14.5/10HPFs were 52.5 and 48 months, respectively, and their respective hazard ratio was significantly higher (Log-rank P<0.05). PHH3 exhibited high specificity and sensitivity in diagnosing EPUN. Combined with HEMC, Ki67 and P53, it can assist in the differential diagnosis of EPUN and estimate its clinical progression with high predictive value to a certain extent.

CD105 and CD34 as Markers of Angiogenesis of Urothelial Carcinoma: A Cross Sectional Study

Background Urothelial carcinoma (UC) of the bladder is a major cause of morbidity and mortality throughout the world. The present study was carried out to see the expression of CD105 and CD34 as marker of angiogenesis in UC and study their relationship with grades and muscle invasion. Methods 50 cases of histopathologically diagnosed UC were included. CD105 and CD34 IHC staining was performed. Microvessel density (MVD) evaluation by CD105 and CD34 was compared. The number of microvessels were counted in high power in three hot spots. The highest value obtained amongst three fields were reported as MVD. Statistical analysis was done by (SPSS 28.00 version for windows) using independent t-test. Results There were 45 high grade cases UC 5 low grade cases of UC. Invasive papillary UC was seen in 25 cases (50%) followed by invasive UC seen in 13 cases (26%). Both Lamina propria (LP) invasion and muscularis propria invasion were noted in 16 cases of high-grade urothelial carcinoma. Only LP invasion was seen in 3 cases of low grade and 25 cases of high-grade UC respectively. Evaluation of MVD CD105 and MVD CD34 did not show any significant association of MVD with grade with a p value of 0.214 &amp; 0.429 respectively. Aso there was no significant association of MVD CD105 (p=0.580) &amp; CD34 (p=0.747) with muscularis propria invasion. Overall mean CD105 and CD34 were similar with no statistical difference between the two markers. Conclusion Both CD105 and CD34 can be used as marker to assess angiogenesis. However, there is no significant association of MVD with grade or muscle invasion in UC.

The Role of Immunohistochemical Expression of Annexin A6 in High Grade Urothelial Carcinoma and Cystitis

The Role of Immunohistochemical Expression of Annexin A6 in High Grade Urothelial Carcinoma and Cystitis

Role of GATA-3 Expression in Urothelial Carcinoma and ITS Correlation with p53 by Immunohistochemistry

Background and Objectives: Urothelial carcinomas are known for divergent differentiation, which often poses diagnostic challenges. The use of immunohistochemistry (IHC) markers helps in differentiating these entities and provides insight into tumor pathogenesis. This study is done with the objective of evaluating significant clinicopathological and histomorphological features of urothelial carcinoma and correlating with GATA-3 and P53 staining. Materials and Methods: A total of 59 cases of urothelial tumors were included in this prospective study. Tissue samples were processed, and H and E-stained slides were evaluated and reported as per the WHO/International Society of Urologic Pathology Classification of bladder tumor 2016. IHC for GATA-3 and p53 was performed using respective monoclonal primary antibodies for GATA-3 and p53. Statistical Analysis: The correlation between GATA-3 and other classical clinicopathological parameters was studied by Chi-square test. P &lt;0.05 was considered statistically significant. Results: In the present study, out of 59 cases, there was a male preponderance with an M: F ratio of 7.4:1 and an age range of 25–85 years. High-grade urothelial carcinoma was the most common histologic subtype. GATA-3 expression was seen in 93.2% of cases. There was a statistically significant correlation of GATA-3 expression with hematuria and dysuria. GATA-3 expression was compared with significant histopathological parameters and a significant correlation of the above parameters with GATA-3 expression was observed. High P53 expression was seen in the majority of high-grade tumors, with only a single case of low-grade UC showing strong P 53 reactivity. Conclusion: GATA-3 is a sensitive IHC marker to diagnose urothelial carcinoma. GATA-3 expression intensity and proportion show significant association with histopathological parameters and may play an important role in stratifying high-risk patients.

Urine cytology in patients with gender confirmation surgery and hormone therapy: evaluation of urine cytology performance in an underserved patient population.

There is a practice gap and educational need regarding urine cytology (UC) performance in patients with history of gender confirmation surgery (GCS) and/or hormone therapy (HT). This potentially impacts diagnostic accuracy in this medically underserved population. We report a methodology that identifies relevant cases and evaluates the performance of UC in this cohort. Two institutional pathology archives from 2000 to 2021 were searched using relevant keywords to identify UC specimens from patients with GCS and/or HT for this retrospective study. For each specimen, patient demographics, relevant clinical history, and history of HT and/or GCS were noted. Each case was blindly reviewed by a cytopathologist according to The Paris System. A total of 32 UC specimens from 15 patients with history of GCS and/or HT were identified. There were 13 male to female and 2 female to male transgender patients. The original diagnosis was negative for high-grade urothelial carcinoma (NHGUC) in 24 of 32 (75%) and atypical urothelial cells (AUC) in 8 of 32 (25%) cases. The most common atypical features were irregular nuclear membranes and prominent small nucleoli in 7 of 8 (87.5%). Degenerative changes were present in 5 of 8 (62.5%). On re-review, with relevant clinical history, 100% of cases were re-classified as NHGUC. The original diagnosis of AUC in these cases likely reflects reactive changes post GCS and/or HT. This cohort may be at risk of AUC overdiagnosis, particularly if the pathologist is unaware of this clinical history. Pathologists need to recognize reactive cytomorphologic changes in these patients. Further multi-institutional studies are warranted to expand knowledge about UC performance in these patients.

Clinicopathologic Features of Noninvasive Inverted Urothelial Papillary Tumor.

Clinicopathologic features and recurrence rates of inverted noninvasive urothelial papillary tumors have been poorly characterized to date with few larger studies evaluating long-term outcomes. The spectrum of histomorphology, clinical features, and prognosis of inverted lesions of the urinary bladder are retrospectively reviewed. Archived paraffin-embedded urothelial tumor samples from patients diagnosed with inverted urothelial papillary lesions between January 2005 and June 2020 were collated. A matched control population of patients with exophytic papillary lesions of the urothelium diagnosed during the same time period was randomly selected. The conventional clinicopathologic features of inverted urothelial papillary tumor were evaluated retrospectively and patient demographics, tumor characteristics, recurrence, and survival information were recorded. Lower recurrence rates were observed for inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP) relative to papillary urothelial neoplasms of low malignant potential and for low-grade papillary urothelial carcinoma with an inverted growth pattern (LG-PUCI) relative to low-grade papillary urothelial carcinomas. No recurrence was found among the inverted urothelial papilloma cases. The 2- and 5-year disease-free survival rates were 100.0% and 85.2% for IPUNLMP patients; 94.4% and 80.4% for papillary urothelial neoplasms of low malignant potential; 89.5% and 82.0% for LG-PUCI; 73.7% and 54.6% for low-grade papillary urothelial carcinoma; 40.0% and 20.0% for high-grade papillary urothelial carcinoma with an inverted growth pattern patients and 26.7% and 26.7% for high-grade papillary urothelial carcinoma. Multivariate Cox regression analysis of IPUNLMP and LG-PUCI/high-grade papillary urothelial carcinoma with an inverted growth pattern indicated that tumor number (hazard ratio=4.356; 95% CI: 1.145-16.570; P =0.031) was a powerful prognostic factor for disease-free survival. Noninvasive, papillary urothelial lesions of the bladder tend to have lower recurrence and a better outcome if an inverted growth pattern is shown.

The preliminary efficacy of "quadri-combination" therapy on the treatment of bladder cancer

To investigate the safety and efficacy of "quadri-combination" therapy including maximal transurethral resection of bladder tumor (mTURBT), combined with systemic chemotherapy and immunotherapy, concurrent radiotherapy, and immune maintenance therapy. The clinical data of 8 patients with bladder cancer who could not tolerate or refused radical cystectomy at the Department of Urology, Peking University Cancer Hospital from November 2019 to October 2021 were retrospectively analyzed. There were 5 males and 3 females with a mean age of 69 years. The Eastern Cooperative Oncology Group(ECOG) score was 0 in 6 cases and 1 in 2 cases. There were 5 cases of high-grade urothelial carcinoma (1 case of T3b; 2 cases were T2; 2 cases of T1 stage, with multiple tumors and repeated recurrence), 1 case of high-grade urothelial carcinoma with carcinoma in situ (T1/Tis stage), 1 case of high-grade urothelial carcinoma with squamous differentiation (T3b stage), and 1 case of high-grade urothelial carcinoma with glandular differentiation (T2). All patients underwent "quadri-combination" therapy.The patient's tolerance, success rate of bladder preservation and prognosis were evaluated.The median follow-up time was 22.5 (12-35) months. One patient with high-grade muscle-invasive bladder cancer (T2) received mTURBT, albumin-bound paclitaxel and durvalumab combined therapy for 3 cycles, concurrent radiotherapy, and immune maintenance therapy for 18 months, and the tumor recurrence was found. The pathology was high-grade urothelial carcinoma. Salvage radical cystectomy combined with pelvic lymph node dissection is recommended. The remaining 7 patients were regularly reexamined, and no recurrence or metastasis was found.The 2-year progression-free survival rate was 80%, and the success rate of bladder preservation was 87.5%(7/8). Treatment-related adverse reactions were resolved by symptomatic treatment, and patients' compliance and tolerance were acceptable.The "quadri-combination" bladder-preserving therapy is feasible and well tolerated, but further studies are needed.

Case Report: Metachronous urothelial carcinoma of the renal pelvis following radical cystectomy: a rare case report

Introduction: Bladder carcinoma (BC) is the most common urinary tumor. The most common histologic type of BC is urothelial carcinoma of the bladder (UCB) According to GLOBOCAN 2020 data, there were 573,000 new cases and 213,000 deaths from bladder cancer in 2015. The likelihood of developing upper urinary tract cancer after a bladder tumor were being treated is minimal; nonetheless, such lesions can develop later. Case Report: A 52-year-old man with urothelial carcinoma of the renal pelvis, previously had UCB. Initially, in 2019, he developed hematuria. It was accompanied by dysuria. Every day, the patient smoked 2 packs. The patient denied having a chronic disease. No family history of cancer. At that time, it was discovered that the patient had urothelial bladder cancer following transurethral resection of bladder tumor (TURBT). Histopathology revealed bladder-invasive urothelial carcinoma. The patient then underwent radical cystectomy and ileal conduit. The patient was stable afterward, but during the pandemic period, the follow-up was disturbed. Early in 2021, the patient got hematuria. The patient was referred for a right radical nephrectomy due to a metachronous mass in the right renal pelvis. The histopathological result indicated a high-grade invasive upper urinary urothelial carcinoma. Conclusion: This study reported a case of metachronous urothelial bladder cancer in the upper urinary tract following radical cystectomy. Thorough surveillance in malignancy cases is a mandatory procedure to detect the recurrence of the malignancy and/or the uneventful spreading of the malignancy to other organs. The research regarding the pathophysiology of metachronous malignancy is still being conducted but has shown some promising results.

Survival nomogram for high-grade bladder cancer patients after surgery based on the SEER database and external validation cohort.

The aim of this study was to develop a comprehensive and effective nomogram for predicting overall survival (OS) rates in postoperative patients with high-grade bladder urothelial carcinoma. Patients diagnosed with high-grade urothelial carcinoma of the bladder after radical cystectomy (RC) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. We randomly split (7:3) these patients into the primary cohort and the internal validation cohort. Two hundred eighteen patients from the First Affiliated Hospital of Nanchang University were collected as the external validation cohort. Univariate and multivariate Cox regression analyses were carried out to seek prognostic factors of postoperative patients with high-grade bladder cancer (HGBC). According to these significant prognostic factors, a simple-to-use nomogram was established for predicting OS. Their performances were evaluated using the concordance index (C-index), the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The study included 4,541 patients. Multivariate Cox regression analysis demonstrated that T stage, positive lymph nodes (PLNs), age, chemotherapy, regional lymph nodes examined (RLNE), and tumor size were correlated with OS. The C-index of the nomogram in the training cohort, internal validation cohort, and external validation cohort were 0.700, 0.717, and 0.681, respectively. In the training, internal validation, and external validation cohorts, the ROC curves showed that the 1-, 3-, and 5-year areas under the curve (AUCs) were higher than0.700, indicating that the nomogram had good reliability and accuracy. Theresults of calibration and DCA showed good concordance and clinical applicability. A nomogram was developed for the first time to predict personalized 1-, 3-, and 5-year OS in HGBC patients after RC. The internal and external validation confirmed the excellent discrimination and calibration ability of the nomogram. The nomogram can help clinicians design personalized treatment strategies and assist with clinical decisions.

Ureteroureteral Fistula as a Rare Complication of Ileal Conduit Urinary Diversion: a Case Report

Long-term studies on ileal conduit have shown a complication rate of up to 66%. Fistulas are a rare late complication of ileal conduit. To our knowledge, no data about ureteroureteral fistulas has been published yet. We present the case of a 73-year-old man with non-muscle invasive high-grade urothelial carcinoma of the bladder who failed to BCG due to intolerance and developed a cripple bladder. He underwent a cystoprostatectomy, pelvic lymphadenectomy, and an ileal conduit urinary diversion. Four months after the surgery, a raised creatinine level was discovered. Sonography revealed bilateral hydro-ureteronephrosis. Shortly after, the stomal urinary production became minimal, and a nephrostomy was introduced to the right kidney. As a result, the right- as well as the left-sided hydronephrosis diminished, as assessed by ultrasound. Through a loopogram and anterograde pyelography, a stenosis at the ureteroileal anastomosis as well as a connection between the two ureters was proven. As an endoscopic intervention to resolve the obstruction failed, a re-laparotomy to make a neo-anastomosis from the ureters to the ileal conduit was performed. We suspect that total obliteration of the oral end of the ileal conduit caused fistula formation of the ureters. We would like to address this rare phenomenon as a complication of ileal conduit to be mentioned in the differential diagnosis if the outcome of urine is in question. It is not a simple stenosis of the distal portion of the ureters and demands an adapted surgical reconstructing technique as well.

Dual immunocytochemical staining of annexin A10 and p53 in low-grade and papillary urothelial carcinoma contributes to improvement of diagnostic accuracy in urine cytology.

Urothelial carcinoma (UC) is a common type of human cancer and, although urine cytology is a useful method for identifying high-grade UC (HGUC), its ability to diagnose low-grade UC (LGUC) is limited. The authors previously reported that annexin A10 (ANXA10) expression was strongly linked to both papillary and early stage LGUC and was inversely correlated with p53 expression in upper tract UC (UTUC) and bladder UC. However, it remains largely unknown whether ANXA10 is useful as a diagnostic marker for urine cytology. In this study, the authors used 104 biopsy and 314 urine cytology samples to investigate the efficacy of ANXA10 and p53 expression by immunohistochemistry and immunocytochemistry. In immunohistochemistry analysis, expression levels of ANXA10 and p53 were either weak or absent in noncancerous tissues, whereas ANXA10 overexpression was observed patients with LGUC, and strong expression of p53 was identified in patients with HGUC. In immunocytochemistry analysis, sensitivity was not good for the detection of UC, especially UTUC, by cytology alone, but it was improved by combining cytology with ANXA10 and p53 to detect both bladder UC and UTUC. Receiver operating characteristic curve analysis also confirmed the diagnostic superiority of cytology combining ANXA10 and p53 for the detection of all UCs, including both HGUC and LGUC (area under the curve, 0.84). To the authors' knowledge, this is the first report that the combination of ANXA10 and p53 has potential application as a diagnostic immunomarker for improving the diagnostic accuracy of urine cytology.