Nonmuscle invasive (NMI) urothelial cancer (UC) is associated with varied biological potential. It is characterized by frequent recurrence and progression, which thus worsens the oncological outcome. Nearly three-quarters of NMI UCs recur within 5 years, whereas half can progress during follow-up. Progression is particularly seen in T1 and carcinoma in situ (CIS). Undoubtedly, NMI UC is one of the most expensive cancers to manage. The European Organisation for Research and Treatment of Cancer (EORTC) risk calculator is a commonly used tool for assessing the recurrence and progression potential of a newly diagnosed cancer. The parameters used in the assessment are tumor size and number, pathological stage and grade of the cancer, presence of CIS, and prior recurrence rate. The main advantages of the EORTC tool are its ease of use and the lack of need to run expensive molecular tests. However, reproducibility of pathologic stage and grade is modest, which is a concern to clinicians. Molecular markers have potential for predicting the clinical outcome of NMI UC, given that clinico-pathologic variables are not sufficient for prediction of prognosis in an individual. Significant work has been done in the past 2 decades in understanding the molecular biology of bladder cancer; however, the translational value of this knowledge remains poor. The role for molecular markers in predicting recurrence seems limited because multifocal disease and incomplete treatment are probably more important for recurrence than the molecular features of a resected tumor. Urinary markers have very limited value in prognostication of bladder cancer and are used (mainly as an adjunct to cytology) for detection and surveillance of urothelial cell cancer recurrence. Prediction of progression with molecular markers holds considerable promise. Nevertheless, the contemporary value of molecular markers over clinico-pathologic indexes is limited.
Age Factors ; Biomarkers, Tumor/*metabolism ; Carcinoma, Transitional Cell/*diagnosis/pathology/surgery ; Disease Progression ; Humans ; Prognosis ; Recurrence ; Risk Assessment/methods ; Urinary Bladder Neoplasms/*diagnosis/pathology/surgery

Bladder cancer remains a commonly diagnosed malignancy worldwide, bringing huge economic burden and high morbidity for patients. Assessment of prognostic significance of lymphovascular invasion (LVI) is a critical issue in the surgical management of bladder cancer after transurethral resection or radical cystectomy. A systematic search of PubMed, Embase and Cochrane Library was performed up to Oct 10, 2014 to identify eligible studies. Outcomes of interest were collected from studies comparing overall survival (OS), cancer specific survival (CSS) and recurrence free survival (RFS) in patients with the LVI. Results of studies were pooled, and combined hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for survival were used as the effect size estimation. Funnel plots were done to show the publication bias, while the forest plots and subgroup analyses were used to limit the heterogeneity. A total of 20 studies (10 663 patients) met the eligibility criteria and were included for this meta-analysis. Our pooled results showed that there were significant differences in OS (pooled HR, 1.71; 95%CI, 1.52-1.92; P<0.00001), CSS (pooled HR, 2.25; 95% CI, 1.80-2.81; P<0.00001) and RFS (pooled HR, 1.91; 95% CI, 1.57-2.32; P<0.00001) between the patients with LVI and the patients without LVI. There were significant heterogeneities observed in the studies concerning the relationship between LVI and CSS, RFS. There was no clear evidence of publication bias. When tumor stage was beyond T3, LVI lost its predictive value for CSS and RFS. For the patients who had negative lymph nodes, LVI was still an adverse predictor. Our pooled results demonstrate that LVI indicates poor prognosis of patients with bladder cancer after surgical procedures, and it can be of particular importance in clinical practice. However, these results need to be further confirmed by more adequately designed prospective studies.
Carcinoma, Squamous Cell ; diagnosis ; mortality ; pathology ; surgery ; Cystectomy ; mortality ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Male ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Urinary Bladder Neoplasms ; diagnosis ; mortality ; pathology ; surgery ; Urothelium ; pathology ; surgery

PURPOSE: Inflammation-based prognostic scores including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are associated with oncologic outcomes in diverse malignancies. We evaluated the predictive value of pretreatment prognostic scores in differentiating nonmuscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC). MATERIALS AND METHODS: Consecutive transurethral resection of bladder tumour (TURBT) cases from January 2011 to December 2013 were analysed retrospectively. Patient demographics, tumour characteristics and prognostic scores results were recorded. Receiver operating characteristics curves were used to determine prognostic score cutoffs. Univariate and multivariate binomial logistic regression analysis was performed to evaluate the association between variables and MIBC. RESULTS: A total of 226 patients were included, with 175 and 51 having NMIBC (stages Ta and T1) and MIBC (stage T2+) groups, respectively. Median age was 75 years and 174 patients were male. The NLR cutoff was 3.89 and had the greatest area under the curve (AUC) of 0.710, followed by LMR (cutoff<1.7; AUC, 0.650) and PLR (cutoff>218; AUC, 0.642). Full blood count samples were taken a median of 12 days prior to TURBT surgery. Multivariate logistic regression analysis identified tumour grade G3 (odds ration [OR], 32.848; 95% confidence interval [CI], 9.818-109.902; p=0.000), tumour size> or =3 cm (OR, 3.353; 95% CI, 1.347-8.345; p=0.009) and NLR> or =3.89 (OR, 8.244; 95% CI, 2.488-27.316; p=0.001) as independent predictors of MIBC. CONCLUSIONS: NLR may provide a simple, cost-effective and easily measured marker for MIBC. It can be performed at the time of diagnostic flexible cystoscopy, thereby assisting in the planning of further treatment.
Aged ; Aged, 80 and over ; Blood Platelets/pathology ; Carcinoma, Transitional Cell/complications/pathology/*surgery ; Female ; Humans ; Inflammation/diagnosis/*etiology ; Leukocyte Count ; Lymphocyte Count ; Male ; Muscle, Smooth/pathology ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neutrophils/pathology ; Platelet Count ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Urinary Bladder Neoplasms/complications/pathology/*surgery

PURPOSE: To investigate the usefulness of urine cytology in the detection of tumor recurrence in terms of practicality and cost-effectiveness. MATERIALS AND METHODS: We retrospectively analyzed 393 patients who underwent transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer (NMIBC) from January 2010 to June 2013. All patients underwent cystoscopy, urine cytology, urinalysis, and computed tomography (CT) at 3 and 6 months after TURBT. In 62 cases, abnormal bladder lesions were identified on cystoscopy within 6 months. Suspicious lesions were confirmed pathologically by TURBT or biopsy. Patients were grouped by modalities: group I, urine cytology; group II, CT; group III, urinalysis; group IV, urine cytology plus CT; group V, urine cytology plus urinalysis; group VI, CT plus urinalysis; group VII, combination of all three modalities. Each group was compared by cost per cancer detected. RESULTS: Forty-nine patients were confirmed to have tumor recurrence and 13 patients were confirmed to have inflammation by pathology. The overall tumor recurrence rate was 12.5% (49/393) and recurrent cases were revealed as NMIBC. Sensitivity in group I (24.5%) was lower than in group II (55.1%, p=0.001) and group III (57.1%, p<0.001). However, in group VII (77.6%), the sensitivity was statistically similar to that of group VI (75.5%, p=0.872). Under the Korean insurance system, total cost per cancer detected for group VII was almost double that of group VI (p=0.041). CONCLUSIONS: Routine urine cytology may not be useful for follow-up of bladder cancer in terms of practicality and cost-effectiveness. Application of urine cytology needs to be adjusted according to each patient.
Aged ; Aged, 80 and over ; Cost-Benefit Analysis ; Cystoscopy/economics ; Cytodiagnosis/economics/methods ; Female ; Health Care Costs/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/economics/pathology ; Neoplasm Staging ; Republic of Korea ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed/economics ; Urinalysis/economics/methods ; Urinary Bladder Neoplasms/*diagnosis/economics/pathology/surgery ; Urine/*cytology

OBJECTIVETo study the clinicopathologic features and prognosis of plasmacytoid urothelial carcinoma (PUC) of the urinary bladder.

METHODSThe clinical and pathologic findings of 16 cases of PUC were retrospectively reviewed. Immunohistochemical study (MaxVision method) was carried out. The follow-up data were analyzed.

RESULTSThere were altogether 15 males and 1 female. The age of patients ranged from 40 years to 85 years (median = 64 years). Most patients (15/16) presented with hematuria. The tumor cells were small to medium in size and contained eccentric nuclei and moderate to abundant eosinophilic cytoplasm, assuming a plasmacytoid appearance. The architectural pattern varied from loosely cohesive sheets to cords, papillae, small nests or gland-like structures. Most tumors invaded into the lamina propria or muscularis propria. Twelve of the 16 cases had concurrent conventional urothelial carcinoma component. Immunohistochemical study showed that the tumor cells in all cases were strongly positive for AE1/AE3, epithelial membrane antigen, CK7 and CK18. CK20 and uroplakin III were also expressed in 9 cases. CEA, p53, CD138, p63 and E-cadherin were positive in 12, 13, 15, 11 and 10 cases, respectively. Ki-67 index ranged from 5% to 70% (mean = 30%). All tumors were negative for vimentin, LCA, kappa/lambda light chains, S-100 protein, HMB 45,Melan A, smooth muscle actin and desmin. Follow-up information was available in 13 patients. The duration of follow up ranged from 3 months to 10 years. Three patients died of distant metastasis at 3, 27 and 60 months after the operation, respectively. One patient was alive with disease at 25 months. One was alive at 43 months with a prior recurrence. Another 8 patients were alive and disease free at 7 to 120 months.

CONCLUSIONSPUC of the urinary bladder is a rare variant of high-grade urothelial carcinoma. Immunohistochemical study with positivity for CK7, CK20, p63 and uroplakin III and negative staining for vimentin and LCA may be helpful in the differential diagnosis. PUC is a malignant tumor with high invasiveness, high recurrence rate and poor prognosis. Radical cystectomy is considered as the first line treatment for PUC.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; metabolism ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; Carcinoma, Transitional Cell ; metabolism ; pathology ; surgery ; Cystectomy ; methods ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Male ; Melanoma ; metabolism ; pathology ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Recurrence, Local ; Plasma Cells ; pathology ; Plasmacytoma ; metabolism ; pathology ; Prognosis ; Retrospective Studies ; Syndecan-1 ; metabolism ; Urinary Bladder Neoplasms ; metabolism ; pathology ; surgery ; Uroplakin III ; metabolism

Antiporters ; metabolism ; Carcinosarcoma ; epidemiology ; metabolism ; pathology ; surgery ; ultrastructure ; Diagnosis, Differential ; Hemangiosarcoma ; pathology ; Humans ; Leiomyosarcoma ; pathology ; Mucin-1 ; metabolism ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Rhabdomyosarcoma ; pathology ; Urinary Bladder Neoplasms ; epidemiology ; metabolism ; pathology ; surgery ; ultrastructure ; Vimentin ; metabolism

OBJECTIVETo study the clinicopathologic features of urothelial hyperplastic lesion with an endophytic growth pattern and the role of immunohistochemistry and multitargeted fluorescence in situ hybridization (FISH) in the differential diagnosis.

METHODSForty-one cases of urothelial lesions exhibiting endophytic growth patterns were reviewed and reclassified as inverted papilloma, urothelial carcinoma with an endophytic growth pattern, and florid von Brunn nest. The gains of chromosomes 3, 7, and 17 and loss of 9p21 was detected by FISH, and performed immunohistochemical staining for CK20, p53, and Ki-67. Follow-up data of 12 cases were obtained.

RESULTS(1) Twelve inverted papillomas sized 1.2 cm in average, consisted of anastomosing cords and nests with uniform width distribution involving the lamina propria, the central portion contained streaming cells with squamous metaplasia, and the periphery showed palisading. No or rare atypia and mitosis were found. Focal exophytic papillary component lined by less than 6 layers of normal urothelium were observed in 4 cases. (2) Twenty-four urothelial carcinomas with an endophytic growth pattern sized 2.1 cm in average, demonstrated the similar architecture with inverted papilloma, but exhibited thick columns and variable thickness of the cords, irregular size and shape of large nests with transition into solids. Mild to moderate cytologic atypia was shown, and mitotic figures ranged 1 to 8 per 10 HPFs. Exophytic papillary component was not observed in 3 cases, but the superficial urothelium showed dysplasia, while coexisted exophytic component in other cases was associated with low malignant potential or low grade tumor. (3) Five florid von Brunn nests sized 0.9 cm in average, had normal or hyperplastic urothelium, variable nests with cysts compacted in lamina propria, no cytologic atypia and mitosis. Twenty-one of 24 (79.1%) urothelial carcinomas with an endophytic growth pattern displayed abnormally positive results by multitargeted FISH, whereas all inverted papillomas and florid von Brunn nests were negative. Immunohistochemically, CK20 was weakly positive in 2 cases of urothelial carcinoma with an endophytic growth pattern, and negative in all inverted papillomas and florid von Brunn nests. p53 weakly stained 5% to 50% nuclei of the tumor cells in 16 cases of urothelial carcinomas with an endophytic growth pattern and 1 inverted papilloma. 1%-5% tumor cells expressed Ki-67 in urothelial carcinoma with an endophytic growth pattern, and less than 1% in inverted papilloma and florid von Brunn nests. Follow-up study revealed that 2 cases of urothelial carcinoma with an endophytic growth pattern had developed invasive carcinoma, underwent cystectomy, and metastasized remotely. No recurrence occurred in cases of inverted papilloma.

CONCLUSIONSBenign and malignant urothelial lesions with an endophytic growth pattern present histologic overlapping. Urothelial carcinoma with an endophytic growth pattern displays unique characteristics in morphology and immunohistochemistry. Multitargeted FISH analysis is helpful in the differential diagnosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Transitional Cell ; genetics ; metabolism ; pathology ; surgery ; Chromosome Aberrations ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Hyperplasia ; In Situ Hybridization, Fluorescence ; Keratin-20 ; metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Papilloma, Inverted ; genetics ; metabolism ; pathology ; surgery ; Tumor Suppressor Protein p53 ; metabolism ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Urothelium ; metabolism ; pathology

We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy.
Adult ; Aged ; Carcinoma, Transitional Cell/diagnosis/*mortality/pathology/*surgery ; *Cystectomy ; Female ; Humans ; Hydronephrosis/classification/*pathology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Urinary Bladder Neoplasms/diagnosis/*mortality/pathology/*surgery

OBJECTIVETo improve the diagnosis and treatment of coincident vesical transitional cell carcinoma (VTCC) and prostate cancer.

METHODSWe analyzed the clinical data of 5 cases of coincident VTCC and prostate cancer.

RESULTSThe 5 patients, at the mean age of 66.2 years, were diagnosed as having grade II - III VTCC by cystoscopy and biopsy, 1 with a history of prostate cancer, and the other 4 with prostate cancer confirmed by postoperative pathological examination. Two of the patients were treated by radical cystoprostatectomy, 1 by radical cystoprostatectomy and ileum conduit surgery, 1 by transurethral resection of bladder tumor, and the other 1 by palliative ureterocutaneostomy due to cardiopulmonary problems. The follow-up lasted 8 -26 months. One of them died of diffused metastasis 20 months after surgery, 1 survived with the tumor untreated, and the other 3 remained tumor free.

CONCLUSIONCoincident VTCC and prostate cancer is easy to be missed in diagnosis. PSA detection, rectal palpation, transrectal ultrasonography, biopsy, and cystoscopy are the main diagnostic options for this disease. Its treatment should be based on the classification and clinical staging of the two cancers. Coincident VTCC and prostate cancer does not suggest poor prognosis.

Aged ; Carcinoma, Transitional Cell ; diagnosis ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Prostatic Neoplasms ; diagnosis ; pathology ; surgery ; Urinary Bladder Neoplasms ; diagnosis ; pathology ; surgery

A 78-yr-old woman presented with gross hematuria for 2 weeks. On cystoscopy, a frond-like mass was observed at the bladder trigone. Transurethral resection of bladder tumor was performed for the mass. Histopathological findings showed that 90% of lesions were lymphoepithelioma-like carcinoma (LELCA) and a few lesions were non-invasive transitional cell carcinoma. On microscopy, syncytial growth pattern and indistinct cytoplasmic borders were observed with the severe infiltration of lymphoid cells. The case was followed-up for 8 months without recurrence. This is the first report of a LELCA case in Korea.
Aged ; Antigens, CD20/metabolism ; Antigens, CD3/metabolism ; B-Lymphocytes/immunology/metabolism ; Carcinoma/*diagnosis/pathology/surgery ; Female ; Hematuria/etiology ; Humans ; Keratin-20/metabolism ; Keratin-7/metabolism ; T-Lymphocytes/immunology/metabolism ; Tomography, X-Ray Computed ; Urinary Bladder Neoplasms/*diagnosis/pathology/surgery