膀胱癌合并上尿路积水患者行根治术的预后分析

目的 探讨术前合并上尿路积水对根治性膀胱切除患者预后的影响.方法 回顾性分析从2003年1月至2010年5月期间126例行根治性膀胱切除术患者的资料,上尿路积水39例(31.0%),单因素分析上尿路积水对膀胱癌患者术后无复发生存率的影响,多因素分析上尿路积水、病理T分期和盆腔淋巴结转移情况等因素对膀胱癌根治术患者术后预...     

Prognostic significance of adjuvant cisplatin-based combination chemotherapy following radical cystectomy in patients with invasive bladder cancer

Objectives: The objectives of this study were to retrospectively examine the outcomes of adjuvant cisplatin‐based combination chemotherapy following radical cystectomy in patients with invasive bladder cancer in order to identify parameters predicting the prognosis of these patients. Methods: This study included a total of 51 patients with muscle invasive bladder cancer who underwent radical cystectomy between January 1995 and December 2004, and subsequently received at least two cycles of either MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) or MVP‐CAB (methotrexate, doxorubicin, vincristine, cyclophosphamide, bleomycin and cisplatin) chemotherapy in an adjuvant setting because of the presence of diseases corresponding to pT3/4 and/or pN1/2 without clinical evidence of metastasis. The significance of several clinicopathological factors as predictors of disease recurrence and cancer‐specific death was evaluated using univariate and multivariate analyses. Results: During the observation period of this study (median, 26.5 months), disease‐recurrence and cancer‐specific death were observed in 21 and 16 patients, respectively. The 5‐year recurrence‐free and cancer‐specific survival rates were 48.6% and 54.1%, respectively. Among several factors examined in this series, lymph node metastasis and concomitant carcinoma in situ (CIS) were identified as significant predictors of both disease‐recurrence and cancer‐specific death, and these were also independently associated with disease‐recurrence and cancer‐specific death. Conclusions: Adjuvant cisplatin‐based combination chemotherapy for patients with extravesically extended bladder cancer following radical cystectomy resulted in comparatively unsatisfactory outcome concerning cancer‐control; accordingly, it would be necessary to develop a more efficacious therapeutic strategy for such patients, particularly for those with lymph node metastasis and/or concomitant CIS.     

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.     

Prognostic value of computed tomography before radical cystectomy in patients with invasive bladder cancer: imaging predicts survival

Purpose

Computed tomography (CT) is current standard-of-care for preoperative staging in patients with invasive bladder cancer before radical cystectomy (RC). There are only sparse data on the association between preoperative CT findings and postoperative survival of patients.

Methods

We retrospectively evaluated preoperative CTs of 206 patients with invasive bladder cancer undergoing RC in an academic tertiary referral center. CTs were analyzed retrospectively for relative bladder wall thickness (BWT) and size of lymph nodes (LN). Associations between CT findings and risk of death from any cause (AC) as well as risk of death from bladder cancer (BC) were assessed by Kaplan–Meier estimates, cumulative incidence curves and multivariable Cox regression analysis.

Results

The median follow-up was 40 months. Increased BWT was significantly correlated with higher risk of death (AC: HR 1.68; p = 0.043; BC: HR 2.00; p = 0.027), as well as LN with a size of 6–10 mm (AC: HR 2.13; p = 0.002; BC: HR 2.77; p = 0.002) and >10 mm (AC: HR 2.47; p = 0.018; BC: HR 3.66; p = 0.007) when compared to LN ≤ 5 mm.

Conclusion

Our data showed a significant correlation of bladder wall thickness and LN size with the risk of death. Also lymph nodes >5 mm but ≤10 mm (resp. ≤8 mm)—usually considered non-pathologic—were associated with a significantly worse prognosis. This information can be used to counsel patients preoperatively. It might also be useful for a risk-adapted approach in regard to neoadjuvant chemotherapy.

     

Impact of marital status in patients undergoing radical cystectomy for bladder cancer

Purpose  Married (vs. unmarried) individuals have improved health status and longer life expectancies in a variety of benign and malignant disease states, including prostate, breast, head/neck, and lung cancers. We sought to evaluate a cohort of patients undergoing cystectomy for bladder cancer to evaluate the impact of marital status on demographic, peri-operative, and pathological outcomes in order to better understand the factors which may contribute to the survival differences observed. Methods  Two-hundred and two patients underwent radical cystectomy and urinary diversion for bladder cancer. Patients were categorized based on marital status as either married or unmarried (widowed, divorced, never married). Correlations were made to demographic factors (age, race, gender, BMI, tobacco use, alcohol use), perioperative factors (pre-op renal function (creatinine), hematocrit, EBL, hospital stay, choice of diversion), and pathological outcomes (organ-confined status, LN positivity). Results  Of the 202 patients, 74% were married. Married individuals (vs. unmarried) were more often male (84 vs. 62%) and had a higher BMI (28.1 vs. 25.9). Married persons had a significantly lower pre-op creatinine (1.1 vs. 1.4) and higher hematocrit (39 vs. 34). Hospital stay was shorter in married patients by a mean of 1.6 days. Regarding operative pathology, married patients had a higher rate of organ-confined disease (59 vs. 47%) (P = 0.05, 0.08 on multivariate) and trended towards a lower rate of LN positivity (15 vs. 21%; P = 0.10, 0.12 multivariate). Conclusions  In patients undergoing cystectomy for bladder cancer, married individuals appear to have improved pre-operative laboratory variables, shorter hospitalization, and improved pathological outcomes versus unmarried patients in our case series. These findings may support the evidence (observed in other tumor types and other disease states) that married persons present earlier than unmarried individuals, and this may help explain the improved survival outcomes that have been observed in married patients with bladder cancer.     

术前白蛋白碱性磷酸酶比值对根治性膀胱切除术后总体生存期的影响

目的探讨术前白蛋白碱性磷酸酶比值(AAPR)与根治性膀胱切除术后患者总体生存期(OS)的关系。方法回顾性分析2007年1月至2015年12月青岛大学附属医院收治的166例膀胱癌患者的临床病理资料。男148例,女18例。年龄(65.1±9.4)岁。伴高血压病31例、糖尿病14例。体质指数(BMI)(24.00±3.32)kg/m^2。肿瘤单发92例,多发74例。肿瘤直径<3 cm者43例,≥3 cm者123例。合并肾积水33例,无肾积水133例。术前AAPR(0.62±0.23)。根据AAPR的三分位点将患者分为低AAPR组55例,AAPR(0.42±0.09);中AAPR组55例,AAPR(0.58±0.05);高AAPR组56例,AAPR(0.86±0.21)。美国麻醉医师协会(ASA)分级1级4例,2级65例,3级86例,4级11例。根治术前患者均行经尿道膀胱肿瘤切除术,病理诊断均为膀胱癌,高级别144例,低级别22例。166例均行根治性膀胱切除术,其中腹腔镜手术140例,开放手术26例。术中行输尿管皮肤造口55例,回肠代膀胱96例,回肠原位新膀胱15例。将AAPR连续性变量和AAPR分组作为原始模型,调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗的数据作为校准模型1,在校准模型1基础上增加BMI、肿瘤数目、病理等级的数据作为校准模型2。采用趋势性检验检测不同AAPR组间危险比(HR)变化趋势。分析不同因素分层的AAPR与OS的关系。采用Kaplan-Meier法绘制生存曲线。采用基于广义相加模型的曲线拟合表示AAPR与OS的关系。结果本组166例中位随访63个月,生存95例,死亡71例。3年生存率为61%,5年生存率为50%。术后病理分期:T1期27例,T2期82例,T3期48例,T4期9例;N0期145例,N1期14例,N2期6例,N3期1例。术后52例行辅助化疗。单因素Cox回归分析结果显示,AAPR(HR=0.09,95%CI 0.022~0.391,P=0.001)、高AAPR组(HR=0.40,95%CI 0.216~0.742,P=0.003)、年龄(HR=2.42,95%CI 1.294~4.531,P=0.006)、肿瘤大小(HR=2.11,95%CI 1.112~4.014,P=0.023)、肿瘤数目(HR=0.62,95%CI 0.378~1.022,P=0.061)、pT3期(HR=8.93,95%CI 3.173~25.114,P<0.001)、pT4期(HR=10.39,95%CI 3.110~34.707,P<0.001)、N1期(HR=2.80,95%CI 1.422~5.531,P=0.003)、N3期(HR=17.06,95%CI 2.192~132.863,P=0.007)、病理分级(HR=0.30,95%CI 0.113~0.817,P=0.019)、肾积水(HR=2.36,95%CI 1.406~3.939,P=0.001)、术后辅助化疗(HR=2.66,95%CI 1.674~4.247,P<0.001)均与术后OS相关。调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗、BMI、肿瘤数目、病理分级后,Cox回归分析结果显示,与低AAPR组相比,高AAPR组的死亡风险降低约59%(HR=0.406,95%CI 0.200~0.822,P=0.012),AAPR每升高1个单位,死亡风险下降约80%(HR=0.199,95%CI 0.051~0.779,P=0.020)。趋势性检验结果显示,原始模型和校准模型中,AAPR不同分组间OS的HR下降趋势均有统计学意义(P=0.016),提示两者呈线性关系。调整年龄、肿瘤大小、pT分期、pN分期、肾积水、ASA分级、辅助化疗、BMI、肿瘤数目、病理分级后,曲线拟合图显示,AAPR与OS呈线性相关,随AAPR升高,术后死亡风险下降,OS延长。结论AAPR与膀胱肿瘤患者根治性膀胱切除术后的OS成线性相关,随AAPR升高,患者术后死亡风险下降,OS延长。     

Prognostic significance of vascular invasion in patients with bladder cancer who underwent radical cystectomy

BACKGROUND: The objective of this study was to determine whether vascular invasion (i.e. lymphatic and blood vessel invasion) could be a useful prognostic predictor in patients with locally invasive transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy. METHODS: This series included 114 consecutive patients undergoing radical cystectomy for primary TCC of the bladder between November 1989 and July 2003. Several clinicopathological characteristics of these patients were analyzed, focusing on the association between vascular invasion and disease recurrence after radical cystectomy. RESULTS: Lymphatic and blood vessel invasions were detected in 55 (48.2%) and 33 (29.8%) specimens, respectively. Lymphatic invasion was significantly associated with pathological stage, tumor grade, lymph node metastasis, blood vessel invasion and disease recurrence, whereas blood vessel invasion was significantly related to pathological stage, lymph node metastasis, lymphatic invasion and disease recurrence. Recurrence-free survival in patients with lymphatic invasion was significantly lower than that in those without lymphatic invasion, and a similar significant difference in recurrence-free survival was observed between patients with and without blood vessel invasion. However, multivariate analysis using the Cox proportional hazards model showed that only pathological stage and lymph node metastasis could be used as independent predictors for disease recurrence after radical cystectomy. CONCLUSIONS: Despite a significant association between several prognostic parameters, vascular invasion was not an independent predictor of disease recurrence; therefore, if there are other conventional parameters available, there might not be any additional advantage to considering the presence of vascular invasion when predicting the prognosis of patients undergoing radical cystectomy for TCC of the bladder.     

Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer

BackgroundTo investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa).Patients and methodsA cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS).ResultsAfter a median 34.2 (22.9–45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524–6.358; P = 0.002), CSS (HR: 4.564, 95% CI: 2.008–10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125–3.739; P = 0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis.ConclusionsPreoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.     

Prognostic significance of Her2/neu overexpression in patients with muscle invasive urinary bladder cancer treated with radical cystectomy

Introduction The aim of the study was to evaluate the status of Her2/neu protein expression in patients with muscle-invasive urothelial carcinomas of the bladder treated with radical cystectomy and to determine its prognostic significance. Material and methods We retrospectively analyzed the data of 90 patients who had undergone cystectomy for invasive transitional cell carcinoma of the urinary bladder. Immunohistochemical analysis for Her2/neu was done on paraffin-fixed tissues with CB11 antibodies (BioGenex, San Ramon, CA, USA). Sections with grade 2 and grade 3 staining were considered positive for Her2/neu. Results Over a median follow-up period of 46 months (24–96 months) 46 patients are living without disease recurrence and six with recurrent disease either at the local site or with distant metastases. The remaining 38 patients have died. The median overall survival time was 50 months, and median disease-free survival time was 40 months. The Her2/neu status was significantly related to the tumor stage (P = 0.001), lymph node involvement (77% in N+ vs 23% in N0; P = 0.001) and the grade of the disease (32% of grade 2 vs 71% of grade 3; P = 0.037). Kaplan–Meier curves showed a significantly worse disease-related survival period (log rank P = 0.011) for patients with Her2 overexpressing tumors than for those without overexpression. In addition to tumor stage [P = 0.001; relative risk (RR) = 2.62] and lymph node status (P = 0.0001; RR = 2.95), Her2 status (P = 0.020; RR = 2.22) was identified as an independent predictor for disease-related survival in a multivariate analysis. Conclusion These results suggest that Her2 expression might provide additional prognostic information for patients with muscle-invasive bladder cancer. Future studies on Her2 expression with chemosensitivity and the efficacy of Her2-targeted therapies in urothelial carcinomas are warranted.     

Prognostic factors in a recent series of patients treated with radical cystectomy for bladder cancer

OBJECTIVE: To identify the clinical and pathological prognostic factors in a homogeneous series of patients with bladder cancer who had undergone radical cystectomy in the late 1990s. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 156 patients who had undergone radical cystectomy and iliac-obturator lymphadenectomy for bladder carcinoma at our department between 1995 and 2001. RESULTS: The mean follow-up was 39.71 +/- 26.2 months. The 5-year overall and cancer-specific survival rates were 47.2 and 54.7%, respectively. Upper urinary tract obstruction (p = 0.03), clinical stage of both the primary tumor (p = 0.0001) and loco-regional lymph nodes (p = 0.04), pathological stage (2002 TNM) of the primary tumor (p < 0.0001), pathological loco-regional lymph node involvement (p < 0.0001), and vascular embolization (p = 0.005) were significant on univariate analysis. Pathological lymph node involvement (p = 0.001) and both pathological (p = 0.022) and clinical stages of the primary tumor (p = 0.002) turned out to be independent predictors of cancer-specific survival. CONCLUSION: Pathological lymph node involvement, clinical and pathological stage of the primary tumor were the cancer-specific, survival-independent, predictors in our series. Our multivariate analysis data identified pT3-4 and pN+ patients as those with the worst prognosis.     

Bladder preservation versus radical cystectomy in transitional cell carcinoma and squamous cell carcinoma muscle invasive bladder cancer

Background:Randomizing patients to bladder preservation or radical cystectomy (RC) for the treatment of bladder cancer has not been practical, due to patient and physician preferences. Therefore, continually comparing the 2 treatment modalities is needed, in order to make the proper choice for each patient.Patients and methods:The records of T1–4N0M0 bladder cancer patients, who presented to the South Egypt Cancer Institute between 2007 and 2017 and were treated by either bladder preservation or RC were reviewed.Results:Out of the 166 included patients, 81 (48.8%) patients were treated by bladder preservation and 85 (51.2%) patients had RC. For the patients treated by bladder preservation and the patients treated by RC, the 5-year overall survival (OS) was 56% and 60% (p = 0.67), the 5-year local recurrence-free survival was 69% and 73% (p = 0.69), and the 5-year disease-free survival was 45% and 53% (p = 0.16), respectively. After propensity matching analysis, the mean 5-year OS was 58% for the bladder preservation patients and 61% for the RC patients (p = 0.51). It is notable that among the bladder preservation group, 8 patients (10%) had squamous cell carcinoma (SCC) pathology and refused RC. Their OS was 56% compared to 53% for the SCC patients treated by RC (p = 0.6).Conclusion:Bladder preservation is a safe alternative to cystectomy in transitional cell carcinoma stages T1–4aN0M0, and its use in SCC bladder cancer should be further studied, as it could be feasible to spare them from initial cystectomy.     

Prognostic significance of tumor markers in colorectal cancer patients: DNA index, S-phase fraction, p53 expression, and Ki-67 index

Risk of colorectal cancer recurrence has traditionally been determined by use of pathologic staging. However, it is apparent that subgroups of patients exist within tumor stages whose clinical behavior differs. This study was undertaken to identify tumor-associated factors that might be predictive of outcome in patients with intermediate stages who will benefit the most from postsurgical adjuvant therapy. Seventy patients with stage II and III colorectal cancer were assessed for DNA indes, S-phase fraction, p53 expression, and Ki-67 index. Tumor recurrence was analyzed by means of nonparametric tests and Cox proportional hazard models incorporating standard clinical and pathologic criteria. Of the four prognostic markers evaluated, Ki-67 index was significantly associated with disease recurrence (P=0.02), whereas DNA index, S-phase fraction, and p53 expression were not. After stratification by tumor stage, significant associations between Ki-67 index and disease recurrence were retained in stage II tumors (P=0.01) but not in stage III tumors (P=0.23). Cox proportional hazard regression analysis indicated that among stage II patients, those with a Ki-67 index >45% were associated with 6.5 times greater risk for disease recurrence than those with a Ki-67 index ≤45%. It was concluded that an elevated Ki-67 index is associated with an increased risk of tumor recurrence in stage II colorectal cancer. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, Calif., May 19–22, 1996.     

Prognostic significance of p53 nuclear overexpression in patients of muscle invasive urinary bladder carcinoma treated with cystectomy

INTRODUCTION: The objective of the study was to determine the pattern of p53 expression in patients with muscle invasive bladder cancer treated with cystectomy and to assess the prognostic value of p53 expression in this group of patients. MATERIALS AND METHODS: We retrospectively analyzed data of 100 patients who underwent cystectomy for invasive transitional cell carcinoma of the urinary bladder. These patients were seen at 3-monthly intervals during the first 2 years, 6-monthly in the third year, and yearly thereafter. Immunohistochemical analysis for p53 was done on paraffin-fixed tissues with DO-7 antibodies. The tumours with >30% cells staining for p53 proteins were considered p53 positive. RESULTS: There were 95 males and 5 females with a mean age of 54 years. Two patients died in the perioperative period and were excluded from analysis. Over a median follow-up period of 2 years (range 3 months to 10 years) 62 patients are alive without disease while 36 had relapse and of these, 31 have died. The p53 expression was significantly related to stage and grade of the tumour. p53-negative tumours were more likely to be organ confined and of lower grade as compared to p53-positive tumours. The stage of tumour was significantly related to outcome but grade and p53 immunohistochemistry did not provide any prognostic information. CONCLUSIONS: p53 immunostaining was positive in 57% of muscle invasive urinary bladder tumours. The p53 positivity correlated well with the stage and grade of the disease, whereas it has no additional prognostic value.     

Prognostic accuracy of an artificial neural network in patients undergoing radical cystectomy for bladder cancer: a comparison with logistic regression analysis

OBJECTIVE: To compare the prognostic performance of an artificial neural network (ANN) with that of standard logistic regression (LR), in patients undergoing radical cystectomy for bladder cancer. PATIENTS AND METHODS: From February 1982 to February 1994, 369 evaluable patients with non-metastatic bladder cancer had pelvic lymph node dissection and radical cystectomy for either stage Ta-T1 (any grade) tumour not responding to intravesical therapy, with or with no carcinoma in situ, or stage T2-T4 tumour. LR analysis based on 12 variables was used to identify predictors of overall 5-year survival, and the ANN model was developed to predict the same outcome. The LR analysis, based on statistically significant predictors, and the ANN model were the compared for their accuracy in predicting survival. RESULTS: The median age of the patients was 63 years, and overall 201 of them died. The tumour stage and nodal involvement (both P<0.001) were the only statistically independent predictors of overall 5-year survival on LR analysis. Based on these variables, LR had a sensitivity and specificity for predicting survival of 68.4% and 82.8%, respectively; corresponding values for the ANN were 62.7% and 86.1%. For LR and ANN, the positive predictive values were 78.6% and 76.2%, and the negative predictive values were 73.9% and 76.5%, respectively. The index of diagnostic accuracy was 75.9% for LR and 76.4% for ANN. CONCLUSIONS: The ANN accurately predicted the survival of patients undergoing radical cystectomy for bladder cancer and had a prognostic performance comparable with that of LR. As ANNs are based on easy-to-use software that can identify nonlinear interactions between variables, they might become the preferred tool for predicting outcome.