Association of vitamin-D receptor (Fok-I) gene polymorphism with bladder cancer in an Indian population

OBJECTIVE: To explore the association of vitamin-D receptor (VDR) genotypes and haplotypes (variants at the Fok-I, and Taq-I sites) with the risk of bladder cancer, as vitamin D is antiproliferative and reported to induce apoptosis in human bladder tumour cells in vitro. PATIENTS, SUBJECTS AND METHODS: A case-control study using polymerase chain reaction-restriction fragment length polymorphism was conducted in 130 patients with bladder cancer and 346 normal healthy individuals in a north Indian population. Patients were also categorized according to grade and stage of tumour. RESULTS: There was a significant difference in genotype and allelic distribution of VDR (Fok-I) polymorphism in the patients (P = 0.033 and = 0.017, respectively). The FF genotype was associated with twice the risk for bladder cancer (odds ratio 2.042, 95% confidence interval, CI, 0.803-5.193). There was no significant difference in genotypic distribution or allelic frequencies of the VDR (Taq-I) polymorphism (P = 0.477 and 0.230) when compared with the controls. The stage and grade of the bladder tumours had no association with VDR (Fok-I and Taq-I) genotypes. There was a significant difference in the frequency distribution of the haplotypes FT and fT (P < 0.001); these haplotypes had a protective effect in the control group (odds ratio 0.167, 95% CI 0.096-0.291, and 0.079, 0.038-0.164). CONCLUSION: These data suggest that VDR (Fok-I) polymorphism is associated with the risk of bladder cancer. Further, the results for the haplotype FT and fT indicate that patients with this haplotype have a lower risk of developing bladder cancer than those with other haplotypes.     

Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology

OBJECTIVE: To evaluate patients with a history of transitional cell carcinoma (TCC) of the upper urinary tract (UUT) to determine the incidence, pathological distribution, and risk factors for developing subsequent bladder tumours. PATIENTS AND METHODS: Between 1993 and 2003, 103 patients were treated at our institution for UUT-TCC. We reviewed demographic, clinical, surgical, and pathological data from these patients at a median follow-up of 38.7 months, and used univariate and multivariate analyses with logistic regression modelling to determine prognostic variables for bladder recurrences. RESULTS: In all, 51 (49.5%) patients developed bladder tumours after treatment for UUT-TCC, at a mean interval of 13.2 months. Patient age (P = 0.01), UUT tumour size (P = 0.03), UUT tumour multifocality (P = 0.05), a history of bladder tumours (P = 0.03), and the number of previous bladder tumours (P = 0.05) predicted the development of bladder recurrences on univariate analysis. On multivariate analysis, only a previous history of bladder tumours (odds ratio 2.6, P = 0.05) remained significant. Over 90% of the recurrent bladder tumours were superficial, with two-thirds of these being low to moderate grade. Six patients had muscle-invasive disease, and five had a cystectomy. CONCLUSION: Bladder tumours occurred in half the patients after treatment for UUT-TCC; > 60% of these subsequent bladder tumours were superficial, low- to moderate-grade lesions. Neither the pathology of the UUT tumours nor the method of treatment for the UUT disease was associated with recurrent bladder tumours. Only a history of bladder cancer predicted the development of subsequent bladder tumours.     

影响肾盂输尿管癌预后的多因素分析

目的 探讨影响肾盂输尿管癌患者的预后因素. 方法回顾性分析220例经病理证实的肾盂输尿管癌患者资料.男146例,女74例.年龄38～84岁.肾盂癌103例,输尿管癌84例,肾盂癌合并输尿管癌13例,肾盂癌合并膀胱癌5例,输尿管癌合并膀胱癌11例,肾盂癌、输尿管癌、膀胱癌同时发生4例.TNM分期:Ta2例、T1116例、T248例、T337例、T417例;WHO分级:G15例、G287例、G3128例.选择11个对预后可能产生影响的因素,应用Cox比例风险回归分析各因素与术后生存率的关系,生存率分析采用Kaplan-Meier方法.生存分析比较采用Gehan比分检验和Log-rank时序检验.应用logistic回归分析各因素与术后再发膀胱癌的关系. 结果 Ta～T1患者5年生存率为80.5%(95/118),T2为70.8%(34/48),T3为45.9%(17/37),T4为17.6%(3/17),Ta～T1、T2与T3～T4之间比较差异有统计学意义(u=9.429,P=0.002).输尿管肾镜术治疗组生存率与其他手术组生存率分析比较,差异无统计学意义(x2=0.217,P=0.641).影响肾盂输尿管癌患者长期生存率的因素为年龄(RR=1.639,P-0.027)、症状初发到手术时间(RR=1.279,P=0.019)、肿瘤分期(RR=1.373,P=0.011).与术后再发膀胱癌显著相关的因素足肿瘤多部位生长(RR=11.292,P=0.003)及伴发膀胱癌(RR=8.780,P=0.001). 结论 年龄、症状初发到手术时间、肿瘤分期是影响肾盂输尿管癌患者长期存活的危险因素,肿瘤多部位生长及伴发膀胱癌是术后再发膀胱癌的高风险因素.     

The role of haematuria in bladder cancer screening among men with former occupational exposure to aromatic amines

Study Type – Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Microscopic haematuria (µH) is frequently detected in elderly adults. The American Urological Association recommends the follow‐up of subjects with µH on bladder cancer. Whereas gross haematuria is considered an important sign of the presence of bladder cancer, the disease‐predictive value of µH is less clear. No association of µH with the development of bladder tumours in a prospective screening cohort of chemical workers was observed. The positive predictive value of µH for bladder cancer was as low as 1.2%. Haematuria interfered with NMP22 but not with cytology and UroVysion^TM test results.

OBJECTIVE

? To assess the positive predictive value (PPV) of microhaematuria (µH) and gross haematuria (GH) in bladder cancer screening and the influence of haematuria on tumour tests in a prospective study.

PATIENTS AND METHODS

? From September 2003 to January 2010, 1323 men took part in an annual voluntary bladder cancer screening programme for chemical workers with former exposure to aromatic amines. ? In 5315 urine samples haematuria was determined with a dipstick, followed by a microscopic blood cell count in the sediment. Haematuria was categorized into traces, µH and GH. ? Urinary leukocytes and other factors were investigated as potential predictors of haematuria using a generalized estimating equation model for repeated urinalysis. The risk of haematuria for positive tumour tests was analysed correspondingly. ? The bladder cancer risk was estimated for the highest degree of haematuria occurring during the study with Poisson regression.

RESULTS

? As of July 2010, 15 bladder tumours were detected in 14 participants. ? GH was found in four out of nine high‐grade tumours and associated with a rate ratio of 3.82, 95% confidence interval (CI) 0.50–29.15 for the development of bladder lesions. ? The PPV of GH was 11.4%, but only 1.2% for µH. µH occurred in 18.8% of urine samples and was not associated with bladder cancer [rate ratio (RR) 0.72, 95% CI 0.11–4.78]. ? Abundant urinary leukocytes were associated with µH [odds ratio (OR) 8.34, 95% CI 2.26–30.69] and even stronger with GH (OR 22.25, 95% CI 6.42–77.06). ? Haematuria and leukocytes influenced NMP22 positivity (µH: OR 1.63, 95% CI 1.06–2.51, abundant leukocytes: OR 8.90, 95% CI 1.58–50.16), but not test results for urine cytology and UroVysion^TM.

CONCLUSION

? While the PPV of µH for bladder cancer was low, there was a strong influence of haematuria and leukocytes on the protein‐based tumour test NMP22®. ? Erythrocytes and leukocytes should be determined at least semi‐quantitatively for the interpretation of positive NMP22 test results. ? In addition, a panel of tumour tests that includes methods not affected by the presence of erythrocytes or leukocytes such as cytology and UroVysion^TM would improve bladder cancer screening.     

Transitional cell carcinoma of the upper urinary tract: prognostic variables and post-operative recurrences

In a retrospective study of 198 patients with transitional cell carcinoma of the upper urinary tract, post-operative recurrences developed as contralateral tumours in 2.5%, in the ureteric stump after conservative resection in 19% and in the bladder in 36.4%. Upper tract recurrences resembled the primary tumours in terms of grade and stage; of the bladder tumours, 89% were similar in grade and 72% similar in stage to the primary tumours. Age, sex, grade and stage had no effect on the number of bladder recurrences, but ureteric tumours had significantly more recurrences than renal pelvicaliceal tumours. Sex, bladder recurrences and site of primary tumours did not influence survival. Thus grade and stage of the primary tumour were the only predictive variables of the final outcome.     

The impact of transurethral resection of bladder tumour on serum levels of soluble E-cadherin

OBJECTIVE: To evaluate soluble E-cadherin (sE-cadherin) as a potential tumour marker in patients with transitional cell carcinoma (TCC) of the bladder (previously shown to correlate with tumour grade, number of Ta/T1 tumours at presentation and a positive 3-month check cystoscopy) by assessing its serum concentration in relation to transurethral resection of bladder tumour (TURBT). PATIENTS AND METHODS: Samples of venous blood were obtained from 25 patients with bladder cancer: (i) before cystoscopy/TURBT: (ii) intraoperatively, during tumour resection; and (iii) on the first day after surgery. Levels of sE-cadherin were measured using an enzyme-linked immunosorbent assay. RESULTS: Sixty-three serum samples from patients with TCC of the bladder were available for analysis (23 before, 21 during and 19 after surgery). Patients with G2/3 tumours had significantly higher median preoperative levels of sE-cadherin (16.37 and 13.03 microg/mL, respectively) than those with G1 tumours (9.493 microg/mL; P = 0.0164). There was no correlation between tumour stage and preoperative sE-cadherin concentration. The median concentrations of sE-cadherin were not significantly different before, during and after TURBT. CONCLUSIONS: This study confirmed the previous finding that higher levels of serum sE-cadherin correlate with increasing tumour grade but not with clinicopathological stage. Serum sE-cadherin levels are not significantly altered by TURBT in the immediate perioperative period.     

Prognostic significance of p27Kip1 expression in bladder cancer

The importance of markers in urological cancer is well recognised and many attempts are being made to find one which will be of prognostic significance. Authors from New York found that low expression of p27Kip1 in patients with bladder cancer was a significant predictor of pelvic recurrence, progression to metastasis and death. Authors from Switzerland examined patients with a primary solitary distal ureteric TCC; they found that distal ureteric resection in such patients is feasible, and that the long-term oncological outcome appears to be comparable to more radical treatment of this condition. OBJECTIVE: To define the prognostic significance of p27(Kip1) expression in bladder cancer for overall, disease-specific, metastasis-free and pelvic recurrence-free survival, and to identify clinical and pathological correlates of p27(Kip1) immunophenotypes. PATIENTS: AND METHODS: Tumour samples from 128 evaluable patients with bladder cancer were assessed by immunohistochemistry for p27(Kip1) and E2F-1 expression. Immunoreactivity of p27(Kip1) was correlated with clinicopathological variables, E2F-1 immunoreactivity, and outcome. Multivariate analysis was used to assess predictors of outcome. The median follow-up was 30.9 months overall and 105.7 months in the 32 patients alive at the last follow-up. RESULTS: The fraction of tumour cells with p27(Kip1) nuclear immunoreactivity was <5% in 15, 5-25% in 30, 25-50% in 19, 50-75% in 51, and > or = 75% in 13 patients. High-grade tumours and those with lower E2F-1 nuclear reactivity had a lower mean percentage p27(Kip1) reactivity (P = 0.047 and 0.011, respectively). On multivariate analysis, the percentage p27(Kip1) reactivity was a significant independent predictor of pelvic recurrence (P = 0.017), progression to metastases (P = 0.046), death from disease (P = 0.008), and death from any cause (P = 0.017), with a low expression portending a worse prognosis. Suspicion of vascular invasion was a significant independent predictor of progression to metastases (P = 0.002), death from disease, and death from any cause (both P < 0.001). Lymph node involvement was a significant independent predictor of progression to metastases (P = 0.006). CONCLUSIONS: Low expression of p27(Kip1) was a significant independent predictor of pelvic recurrence, progression to metastasis, death from disease and death from any cause, in patients with bladder cancer.     

Independent prognostic value of tumour diameter and tumour necrosis in upper urinary tract urothelial carcinoma

OBJECTIVE

To identify significant prognostic indicators of upper urinary tract (UUT) urothelial carcinoma (UC) and to assess a risk stratification of patients.

PATIENTS AND METHODS

We retrospectively analysed data from 162 patients with non‐metastatic UC primarily occurring in UUT treated with open nephroureterectomy. Variables assessed included age, gender, pT, tumour grade, tumour necrosis extension, pN, tumour location, multifocal location, tumour diameter, and subsequent development of a bladder tumour. Tumour necrosis was measured using commercial software (Eureka interface system, version 4.0.22, HESP technology, Menarini Diagnostics, Italy) and was classified as none, focal (<10% of tumour area) or extensive, ≥10% of tumour area). The prognostic significance of each variable on metastasis‐free survival (MFS) and disease‐free survival (DFS) was tested in univariable analysis with the log‐rank test. Variables with significance levels of P < 0.05 according to the univariable analyses were entered into a multivariable forward‐stepwise Cox regression model.

RESULTS

At a mean follow‐up of 66 months, 20 cancer‐related deaths (12.3%) were censored. In multivariable analysis, tumour diameter, pT stage and tumour necrosis were independent predictors of MFS and DFS. All events occurred in patients with extensive tumour necrosis and a tumour diameter of ≥3 cm. The median survival of patients with advanced‐stage tumours, extensive necrosis and a tumour diameter of ≥3 cm were significantly impaired by increasing pT stage(P < 0.001).

CONCLUSION

Tumour necrosis and tumour diameter are compelling prognostic factors that deserve further study in a prospective setting to determine if their use in combination with more traditional variables, such as pT stage, might better determine prognosis and guide the follow‐up and treatment of patients.     

Urine tissue-polypeptide-specific antigen (TPS) as a marker for bladder cancer.

OBJECTIVES: To determine the sensitivity and specificity of urine tissue-polypeptide-specific antigen (TPS) for bladder carcinomas and to evaluate whether urine TPS is influenced by tumour size, number, grade and stage. PATIENTS AND METHODS: A total of 260 patients entered the study, one group (n = 151) with known bladder cancer disease (79 with recurrent tumour and 72 with no tumour at cystoscopy). The other group (n = 109) consisted of patients without previously known bladder tumour disease, 55 with newly detected bladder tumour(s) and 54 investigated for microhematuria found to be idiopathic. TPS in urine was measured using an ELISA-kit, a solid phase two-site immunosorbent assay with polyclonal antibodies against cytokeratin 18. RESULTS: Urine TPS was significantly higher in patients with bladder tumours (p < 0.001). There was a significant correlation between TPS and tumour size (p = 0.004), grade (p = 0.001) and stage (p = 0.001). Tumour number was not significantly correlated to urine TPS (p = 0.75). With TPS 42 as a cut-off level, the sensitivity was 73% for newly detected tumours and 50% for recurrences; the specificity was 70% and 63% respectively. With a 95% specificity, the sensitivity for newly detected tumours was 33% and for recurrences 18%. The lower sensitivity and specificity for recurrences was mainly explained by differences in tumour size, grade and stage between the recurrences and the newly detected tumours. CONCLUSIONS: Urine TPS is a marker for bladder carcinoma correlated to size, grade and stage. The sensitivity and specificity for newly detected tumours are quite comparable with other markers. Its clinical usefulness is however not established and it appears less useful in the follow-up of patients with known bladder tumour disease.     

Expression of angiopoietin-1 and -2, and its clinical significance in human bladder cancer

OBJECTIVE: To investigate the relationship between angiopoietin-1 and -2 expression and the clinicopathological variables and clinical outcome in patients with bladder cancer treated by surgical resection, as both have been recently identified as antagonistic angiogenic factors which regulate tumour growth. MATERIALS AND METHODS: The expression of angiopoietin-1 and -2 were assessed by immunohistochemistry in tissue sections from 52 transitional cell carcinomas of the bladder (33 grade 1, 15 grade 2, four grade 3, including two associated with carcinoma in situ; 22 were stage Ta, 19 T1 and 11 T2 tumours). Normal bladder specimens were also resected during each operation as controls. The expression angiopoietins were related to the clinicopathological variables of the tumours. RESULTS: Positive immunostaining was detected in 18 samples (35%) for angiopoietin-1 and in 23 (44) for angiopoietin-2. There was no significant difference in survival according to tumour angiopoietin-1 status in the patients, but in contrast the overall survival of patients with angiopoietin-2-positive tumours was significantly lower than for those with angiopoietin-2-negative tumours (P < 0.05). Positive angiopoietin-2 expression was significantly correlated with histological grade (P = 0.026), histological stage (P = 0.009) and poor prognosis (P < 0.05). On multivariate analysis, positive angiopoietin-2 expression was an independent negative predictor for survival (P = 0.042). CONCLUSIONS: These results suggest that angiopoietin-2 overexpression is associated with tumour progression, thereby indicating a poor prognosis for some patients treated by surgical resection for bladder carcinoma.     

Upper urinary tract transitional cell carcinoma after total cystectomy for bladder cancer

During a 17-year-period from 1967 to 1983, 110 total cystectomies for transitional cell bladder cancer have been performed in our clinic. During the postcystectomy period, upper urinary tract urothelial cancer developed in seven patients (6.4%). In every case a multifocal, low stage transitional cell cancer had been found in the bladder. The time between the cystectomy and discovery of the upper tract tumour varied from less than three months to almost 13 years. In five cases the first sign of occurrence of the tumour was malignant conduit urine cytology, in two macroscopic haematuria with subsequent malignant cells in urine. In one patient bilateral renal pelvic tumours were found. Five patients could be surgically treated. The need for regular conduit urine cytological studies at short intervals in patients with multifocal low stage and high grade transitional cell carcinoma in the cystectomy specimen is emphasised.     

Evolución y pronóstico a medio y largo plazo de los tumores vesicales superficiales

ObjetivesTo evaluate the outcome of 551 patients with superficial transitional cell carcinomas of the bladder. To determine prognostic factors in these patients by means of the log-rank analysis of the Kaplan-Meier curves and a multivariate analysis with Cox regression model for the disease free survival (DFS), time to progression to infiltrating lesions (TTP) and overall survival (OS)Material and methodsBetween 1983 and 1998 we have seen 551 patients with superficial transitional cell carcinomas of the bladder in our Hospital. Fifteen patients included in this series had been diagnosed in other hospitals before 1983. The clinical records were actualized between 1998 and 2000 and only 21 patients were lost to follow-up (3,8%). The mean follow-up time was 6,2 years (median time: 5,3). One hundred and eleven patients (20%) died with a mean of 4,5 years (median time 3,4). Four hundred and forty patients were still alive on completion of the study with a mean follow-up time of 6,6 years (range 2-24 years; median 5,7)ResultsFour hundred and fifty-nine patients were men (83%) with a mean age of 64 years and 92 were women (17%) with a mean age of 70 years. In 347 patients there was only one tumour (63%). The tumours were stage Ta in 79 cases (14%), T 1 in 431 (78%) and Tis in 41 (7%). The histological grade was G 1 in 406 cases (74%), G 2 in 96 (17%) and G 3 in 33 (6%)There were recurrences in 253 patients (46%) with a mean time of 2.2 years. The DFS was 55% at 5 years, 44% at 10 years and 38% at 15 years. The multivariate analysis has shown a negative prognostic influence on DFS of the presence of multiple tumours (RR 1.4 CI 1.19-1.69), increasing age (analysed as a continuous variable) and the sex (being worse for females; RR 1.2 CI 0.98-1.52)In 40 patients (7.3%) the tumour became infiltrative in a mean of 3.3 years. The TTP was 93% at 5 years, 91% at 10 years and 90% at 15 years. The negative prognosticators in the multivariate analysis were G 3 tumour (RR: 5.1 CI 2.7-9.6), the group of tumours Ta-T 1 G 3 or multiple T 1 G 2 or Tis (RR 4.6 CI 2.6-7.9) and the age>70 years (RR 2.14 CI 1.2-3.7)Thirthy-one patients (5.6%) died of the tumour in a mean time of 4.6 years. The OS was 95% at 5 years, 93% at 10 years and 91% at 15 years. Significant prognosticators in the multivariate analysis for OS were the group of risk tumours Ta-T 1 G 3 and multiple Tis or T 1 G 2 (RR 5 CI 2.7-9) and age>70 years (RR 4.56 CI 2.2-8.8)ConclusionsThe recurrence rate is very high in all the patients, but the risk is highest when the tumours are multiple. The risk of progression is low, but still exits even in patients with tumours of low malignant potential. The highest risk is associated with Ta-T 1 G 3 of Tis or multiple T 1 G 2     

Prognostic significance of tumour angiogenesis in schistosoma-associated adenocarcinoma of the urinary bladder

OBJECTIVE: To report on tumour angiogenesis and its relationship with morphological variables and prognosis in adenocarcinoma of the urinary bladder associated with schistosomiasis. PATIENTS AND METHODS: Fifty-five vesical adenocarcinomas were evaluated from 30 men and 25 women (mean age 47.2 years, sd 8.7, range 30-65) who were followed up after radical cystectomy and urinary diversion for a mean (sd, range) of 61 (43.5, 2.7-159.5) months. Vessels were stained immunohistochemically using an antibody to the platelet endothelial cell-adhesion molecule CD31. Microvessels were counted in active areas of angiogenesis within the tumours (at x250) and the microvessel density (MVD) quantified using the mean of three counts. Treatment failure was defined as death from cancer or the development of local recurrence or distant metastasis. Kaplan-Meier survival curves and Cox's proportional hazard model were used to assess survival. RESULTS: The overall 5- and 10-year survival rates were 57% and 51%, respectively. The presence of lymph node metastasis and high mean vascular density (> 26) were significantly associated with a poor prognosis. The 5-year survival for patients with negative lymph nodes was 66% while no patients with positive nodes survived for 5 years (P < 0.001); the survival was 72% for patients with a low MVD and 33% for those with a high MVD (P = 0.0016). From individual results plotted against vascularity in lymph node-negative patients, there was a significantly better outcome for those with a low MVD (< or = 26; P = 0.0099); this significance was maintained on multivariate analysis. However, there was no significant relationship between angiogenesis and the different clinicopathological factors apart from the grade (P = 0.03); tumour stage, grade and DNA profile had no significant effect on survival in these patients. CONCLUSIONS: These findings suggest that assessing angiogenesis using the MVD provides an independent predictor of survival in patients with adenocarcinoma of the urinary bladder.     

Tissue factor and vascular endothelial growth factor expression in colorectal cancer: relation with cancer recurrence

OBJECTIVE: This study was undertaken to quantify tissue factor (TF) and vascular endothelial growth factor (VEGF) in colorectal cancer and to evaluate their possible relationship with recurrence. METHOD: TF and VEGF were measured by enzyme-linked immunosorbent assay in surgical tumour specimens and normal mucosa from 50 consecutive patients with colorectal cancer who were followed up for 3 years for the assessment of disease recurrence. RESULTS: TF and VEGF antigens were detected in all tumour samples. VEGF, but not TF, was much higher in tumour than in normal mucosa (P < 0.0001), as also confirmed by measurement of specific mRNAs. There was a strong correlation between TF and VEGF antigens (P < 0.0005) in tumour tissue but not in normal mucosa. Neither protein was related to tumour stage, grade or size. Local or distant recurrence was statistically related to pTNM stage. High VEGF, but not TF, levels in tumour extracts were associated with an increased risk of recurrence both by univariate (RR, 4.00, 95% CI: 1.45-11.0) and multivariate analyses (RR, 3.65, 95% CI: 1.33-10.0). CONCLUSION: These findings suggest that VEGF content in colorectal cancer is an independent risk factor for tumour recurrence and might help select patients who might benefit from adjuvant therapy.     

Superficial bladder cancer treated by total cystectomy: Tumour characteristics and patient survival

Of 113 patients with bladder cancer who underwent total cystectomy from January 1980 to December 1990, 30 (27%) had superficial tumours (pTa, pTis, and pT1). Nineteen of these 30 patients (63%) were primarily treated by total cystectomy and the remaining 11 (37%) had a past history of treatment for bladder cancer. Major reasons for choice of total cystectomy were multifocal tumours, frequent recurrence, and diffuse carcinoma in situ. Histologically stage pT1, grade 3 tumours were frequently accompanied by carcinoma in situ and often by lymphatic invasion. None of the 24 patients undergoing pelvic lymphadenectomy had lymph node metastasis. Of 25 male patients 15 (60%) underwent simultaneous prophylactic urethrectomy. Two of the remaining 10 males (20%) not undergoing this additional operation died of subsequent urethral recurrence. The 5-year actuarial survival rate was 80% for the 30 patients when all causes of death were considered. It was concluded that patients with superficial bladder cancer who undergo total cystectomy without prophylactic urethrectomy require close follow-up with urethral washings for cytology to detect early urethral recurrence, an important determinant for survival.     

Oncological impact of cystoscopic findings in non-muscle-invasive bladder cancer: a meta-analysis

Objective

To assess the association between cystoscopic findings and oncological outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) given that the oncological impact of quantity and quality assessment of tumours with cystoscopy has not been well verified.

Methods

Multiple databases were queried in May 2022 for studies investigating the association of oncological outcomes, such as recurrence-free (RFS), progression-free (PFS), and cancer-specific survival (CSS), with cystoscopic findings, including multiplicity, size, and gross appearance of tumours in patients with NMIBC.

Results

Overall, 73 studies comprising 28 139 patients were eligible for the meta-analysis. Tumour multiplicity was associated with worse RFS (pooled hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.48–1.74) and PFS (pooled HR 1.44, 95% CI 1.18–1.76) in NMIBC patients (including both Ta and T1). Tumour size (≥3 cm) was associated with worse RFS (pooled HR 1.97, 95% CI 1.69–2.30) and PFS (pooled HR 1.81, 95% CI 1.52–2.15) in NMIBC patients. In patients with T1 bladder cancer (BCa), tumour multiplicity and size (≥3 cm) were also associated with worse RFS, PFS and CSS. By contrast, among patients treated with bacillus Calmette-Guérin (BCG), tumour multiplicity was not associated with worse RFS, and tumour size (≥3 cm) was not associated with worse PFS. Sessile tumours were associated with worse RFS (pooled HR 2.14, 95% CI 1.52–3.01) and PFS (pooled HR 2.17, 95% CI 1.42–3.32) compared to pedunculated tumours. Compared to papillary tumours, solid tumours were associated with worse RFS (pooled HR 1.84, 95% CI 1.25–2.72) and PFS (pooled HR 3.06, 95% CI 2.31–4.07) in NMIBC patients, and CSS in T1 BCa patients (pooled HR 2.32, 95% CI 1.63–3.30).

Conclusions

Cystoscopic findings, including tumour multiplicity, size, and gross appearance, strongly predict oncological outcomes in NMIBC patients. Cystoscopic visual features can help in the decision-making process regarding the timeliness and extent of tumour resection as well as future management such as intravesical therapy.     

Urothelial atypia concomitant with primary bladder tumour. Incidence in a consecutive series of 500 unselected patients

A consecutive series of 500 primary bladder tumours from a single clinic is presented, with distribution of the tumours according to T category and histologic type and grade. Mucosal biopsies were obtained from pre-selected sites at initial cystoscopy or initial transurethral resection of the tumour in 396 cases. In 54% of the patients with grade III tumour there was concomitant urothelial atypia, either carcinoma in situ (urothelial atypia grade III, 30%) or urothelial atypia grade II (24%). In 30% of the patients with invasive grade II bladder tumour and in 14% of those with noninvasive grade II tumour there was concomitant urothelial atypia, mostly grade II. Since concomitant urothelial atypia predicts new tumour growth after successful transurethral surgery or radiotherapy, mucosal biopsies should be performed at preselected sites during initial cystoscopy or transurethral tumour resection in order to identify high-risk patients.     

Outcomes of a bladder preservation technique in female patients undergoing pelvic exenteration surgery for advanced gynaecological tumours

Introduction and hypothesis

The purpose of the study was to report the feasibility of the bladder preservation technique (BPT) during pelvic exenteration for primary advanced gynaecological pelvic tumours (PRSGT) as an alternative for continent urinary diversion.

Methods

Sixteen consecutive female patients underwent BPT during PRSGT. Median age was 50.8 years (range 37–65). Tumours included cervical (5 patients), corpus/vaginal (9), and ovarian (2) carcinomas. In resectable tumours, the excision of the distal ureters and the posterior bladder wall with an inverted “V” incision into the trigone down to the vaginal wall was performed with bladder blood and nerve supply preservation. The remaining mobilized leaflets were fixed to the psoas muscle/sacral promontory. Average follow-up was 34 months (range 24–108). Follow-up parameters included postoperative continence grade (full [no pads], stress incontinence grade I [1–2 pads], and grade II [>2 pads]), urinary tract infections, micturation problems/residual urine, ureteric reflux as well as patients’ global satisfaction (PGS).

Results

All surgeries were done successfully. One patient developed a vesicovaginal fistula 4 weeks postoperatively and was managed conservatively. Fifteen patients (94 %) were able to empty their bladders postoperatively. Prolonged full continence was reported from 8 patients (50 %), incontinence grade I in 3 (18.8 %), and grade II in 5 (31.3 %). Two patients (incontinence grade II) developed cystoceles necessitating transvaginal bladder neck suspension with a fascia lata sling and were continent postoperatively. Another patient (6 %) underwent re-excision of a recurrent pelvic tumour necessitating intermittent self-catheterization. Postoperative hydronephrosis (grade I–II) was observed in 4 patients (25 %) and vesico-ureteral reflux (grade IV) in 4 (25 %) without the need for intervention. PGS and willingness to recommend their procedure to others were favourable.

Conclusions

In patients for whom complete bladder resection is not indicated for oncological reasons, BPT during PRSGT with ureteric reimplantation is feasible and safe and provides good functional results as well as patient global satisfaction. Lower tract surgeries could be safely carried out afterward. Long-term functional results support durable good PGS.     

The impact of tumour location on the histological subtype of renal cortical tumours

OBJECTIVE: To determine whether the location of renal cortical tumours (RCTs) is a possible factor affecting tumour behaviour, by investigating whether exophytic vs a central location is associated with a difference in histological subtype distribution, as recognized prognostic factors for RCTs include size, stage, grade, and histological subtype. PATIENTS AND METHODS: Between 1 January 1996 and 1 June 2003, we evaluated 485 consecutive RCTs in 469 patients who had renal imaging studies and underwent either partial or radical nephrectomy at our institution. A radiologist and a urologist independently reviewed the imaging studies of all patients to determine exophytic vs central location. An exophytic lesion was defined as one that clearly both pushed out the renal contour and did not extend into the collecting system, hilum, or renal sinus. A lesion that did not meet these criteria was defined as a central lesion. Logistic regression analysis was used to determine if either type of lesion had a greater representation of any histological subtype. A two-tailed P < or = 0.05 was considered to indicate significance. RESULTS: Of the 485 RCTs, 171 (35%) were exophytic and 314 (65%) were central, while 308 (64%) were clear cell and 177 (36%) were non-clear cell tumour histology. Of the exophytic lesions, 52.0% were clear cell, while 69.7% of central lesions were clear cell (P < 0.001). Conversely, 71.1% of clear cell tumours were central, while 53.7% of non-clear cell tumours were central (P = 0.003). After controlling for size and stage, tumour location remained associated with histological subtype (P = 0.003). CONCLUSIONS: Exophytic lesions are significantly more likely than central lesions to be non-clear cell tumours, and clear cell tumours are significantly more likely than non-clear cell tumours to be central. As studies indicate that the clear cell histological subtype portends a worse prognosis than the non-clear cell subtype, our results imply that tumour location affects the prognosis in RCTs, with exophytic lesions having a better prognosis than central lesions. This result may have important implications for physicians and patients when planning partial vs radical nephrectomy by either open or minimally invasive techniques.