Risk factors for the development of bladder cancer after upper tract urothelial cancer

OBJECTIVES: To determine the clinical and pathologic risk factors for initial intravesical recurrence in patients with primary renal pelvic and/or ureteral cancer and to examine the progression in the bladder in patients having high risk factors for intravesical recurrence. METHODS: This study included 69 patients with renal pelvic and/or ureteral cancer. We excluded patients with distant metastases, those with a short period of follow-up, and those having a previous history or concomitance of bladder cancer. The exclusion criteria were chosen to avoid contamination by patients with a poor prognosis who might die of the primary cancer before bladder cancer development. Multivariate analysis by Cox's proportional hazards model was used to determine what clinical and pathologic variables significantly affected the initial intravesical recurrence of cancer. We also studied the stage progression of cancer that recurred in the bladder. RESULTS: Initial intravesical recurrence of the cancer was found in 22 patients during a median follow-up period of 53 months (range 12 to 225). The intravesical disease-free rate after upper tract urothelial cancer was 65% (rate of disease recurrence in bladder 35%) at 5 years by the Kaplan-Meier method. The extent (multifocality) of the upper urinary cancer (P = 0.0038) and pathologic stage (P = 0.0409) independently influenced intravesical recurrence. Age, sex, adjuvant chemotherapy, configuration of the primary tumor, primary cancer size, and pathologic grade did not affect recurrence. The rate of stage progression also was not influenced by the extent of the disease in the upper urinary tract. CONCLUSIONS: The extent and pathologic stage of cancer in the upper urinary tract were significant and independent factors for initial intravesical recurrence of cancer. However, no difference was found in clinical outcome in terms of stage progression between patients having high risk factors for intravesical recurrence and those without them.     

Prophylactic intravesical BCG for bladder tumor after surgery of upper tract urothelial carcinoma

We report the result of prophylactic intravesical instillation of BCG after surgery of upper tract urothelial carcinoma. The BCG Tokyo 172 strain was given preoperatively and/or postoperatively, as a rule, in a dose of 80 mg in 30 ml saline instilled into the bladder. Only one (14.3%) of the 7 patients with intravesical BCG developed bladder tumor at 14 month after surgery, while (45.4%) of 11 patients who did not receive intravesical BCG suffered from bladder tumor within 2 years after surgery. Prophylactic intravesical instillation of BCG reduced significantly (p less than 0.005) the recurrence of bladder tumor after the surgery of renal pelvis and ureteral tumor.     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

Muscle-invasive bladder cancer developing after nephroureterectomy for upper urinary tract urothelial carcinoma

ObjectivesTo evaluate the risk factors and prognosis of muscle-invasive bladder cancer (MIBC) developing after nephroureterectomy for upper urinary tract urothelial cell carcinoma (UUT-UC).Materials and methodsWe reviewed the medical records of 422 patients who underwent nephroureterectomy for UUT-UC between 1990 and 2010, and identified 173 (40.9%) with intravesical recurrence and 28 (6.6%) with MIBC. We evaluated the clinicopathologic features, risk factors, and cancer-specific survival (CSS) using the Kaplan-Meier method and the Cox proportional hazards regression models.ResultsThe median intervals from nephroureterectomy to intravesical recurrence and the development of MIBC were 8 and 17 months, respectively. On multivariate analysis, the pathologic stage (≥pT3 vs. Ta/T1, HR 5.03, P = 0.001) and ureteral tumor location (HR 2.79, P = 0.011) were independent risk factors for the development of MIBC, whereas a history of previous or concomitant bladder tumor was the only significant risk factor for intravesical recurrence. The probability of developing MIBC 5 years after nephroureterectomy was 12.6% in patients with 1 risk factor and 20.6% in patients with both risk factors. Patients with MIBC had significantly worse CSS than those without MIBC (P = 0.004), whereas CSS rates were similar in patients with and without intravesical recurrence (P = 0.593). However, stratification analysis for matching pathology revealed that CSS rates were not significantly different in patients with pT2 or higher stage of UUT-UC.ConclusionsApproximately 5% of the patients developed MIBC after nephroureterectomy with a median interval of 17 months. Patients with advanced pathologic stage (≥pT3) and a ureteral tumor location are at increased risk of developing MIBC after nephroureterectomy.     

Skin metastasis of urothelial bladder tumor

We want to present a case of tranticional cell bladder carcinoma, where the first sign of disease progression was the appearance of a skin metastase. An unusual manifestation in a patient without another metastatic lesions.     

预防肾盂输尿管癌术后再发膀胱癌的手术方法研究

目的探讨预防。肾盂输尿管癌术后再发膀胱癌的手术方法。方法对156例单纯。肾盂癌、单纯输尿管癌中获随访的139例患者资料进行同顾性总结。肾盂癌78例。输尿管癌61例。肿瘤细胞分级：G1 19例，G2 88例，G3 32例。肿瘤分期：Ta—T1 38例，T2 80例，T3～T4 21例。肿瘤直径0．8—6．0cm。结果139例均行根治性。肾、输尿管及管口周围部分膀胱壁（1．5—2．0cm）切除术。术后随访1～10年。再发膀胱癌55例，占39．6％。肾盂癌术中先用纱条结扎输尿管后游离切除患肾输尿管及管口周围部分膀胱者术后膀胱癌再发率18．5％（5／27），未先结扎输尿管者再发率27．5％（14／51）。术后当日膀胱灌注化疗者膀胱癌再发率32．3％（10／31）。术后3周开始膀胱灌注化疗者膀胱癌再发率34．9％（30／86）。术后当日及术后序贯膀胱灌注化疗者术后膀胱癌再发率20．0％（4／20），单纯术后序贯膀胱灌注化疗者膀胱癌再发率39．3％（26／66）。2者比较差异有统计学意义（P〈0．01）。结论术后当日及术后序贯膀胱灌注化疗可有效降低。肾盂输尿管癌术后膀胱癌的再发率，游离切除。肾输尿管前先结扎输尿管对预防肾盂癌术后再发膀胱癌可能有益。     

An atypical presentation of upper urothelial tumor

In some cases of primary transitional cell carcinoma (TCC), there may be some uncertainty in clinical decision making. We present a case in which a pT1-N0 urothelial tumor was found in the renal pelvis after an open nephrectomy for urolithiasis. Because incomplete excision of the ureter can lead to recurrence of the TCC, we deemed it necessary to remove the residual ureter. Therefore, a combined endoscopic-transvescical laparoscopic ureterectomy was performed. The transabdominal approach was chosen for the procedure, because the patient had already undergone open nephrectomy with retroperitoneal access and was thus likely to have adhesions and inflammation in the region. For the endoscopic phase of surgery, a technique of ureteral intussusception was combined with transurethral resection. The choice of the endoscopic transurethral procedure was prompted by the fact that transurethral resection of the ureteral orifice and invagination ureterectomy has already been proposed as the first step of nephroureterectomy. The combined endoscopic laparoscopic procedure was not technically demanding; the ureterectomy took no longer than an open procedure. The surgery was uneventful, and the patient resumed normal activities the day after surgery. The broader issue of whether this technique should be adopted by the urological community at large as a routine practice requires longer follow-up outcome data.     

An atypical presentation of upper urothelial tumor

Although intestinal metastases from extraabdominal malignancies are an infrequent occurrence, they may cause obstruction, visceral perforation, or gastrointestinal bleeding. We report a case of upper gastrointestinal bleeding from a metastasis in the body of the stomach in a 69-year-old man with advanced malignant disease treated by laparoscopic wedge resection. Laparoscopic exploration was undertaken under general anesthesia, confirming the position of the tumor on the greater curve of stomach adjacent to the lower pole of the spleen. The greater curve of the stomach was mobilized with the harmonic scalpel. The gastroepiploic arcade was divided below the tumor, and local resection of the tumor was performed. The specimen was removed in a bag. Postoperatively, the patient made an uneventful recovery and was discharged on the 3rd postoperative day. Histological examination of the specimen indicated choriocarcinoma. We conclude that in selected patients with good functional status, resection of bleeding metastatic lesions of the gastrointestinal tract is a useful palliative procedure. Laparoscopic resection is especially advantageous in patients with a limited prognosis because it shortens postoperative stay and enables early resumption of daily activities.     

上尿路移行细胞癌术后发生膀胱癌的危险因素分析

目的探讨上尿路移行细胞癌临床与病理特点及对术后膀胱癌发生及预后的影响.方法对133例肾盂和(或)输尿管癌病例的临床特点与术后发生膀胱癌以及预后情况分别应用Cox比例风险模型分析,作Kaplan-Meier曲线并行LogRank检验.结果133例患者接受根治手术后发生膀胱癌者40例,占30.1%.原发上尿路肿瘤数目、分期和有无同发膀胱癌对术后发生膀胱癌有显著影响,风险度>1,回归系数>0,二者间相关系数小.应用LogRank检验显示原发肿瘤为单发者术后无膀胱癌发生的机率低于多发者(P=0),随着病理分期的升高,膀胱癌发生率随之增加(P＝0.0039).首次发生膀胱癌者有92.5%在2年之内.原发肿瘤数目、分期、有无同发膀胱癌以及术后膀胱癌发生间隔时间对存活率有显著影响,四种因素的相关系数小.结论原发上尿路肿瘤的数目、分期和有无同发膀胱癌为术后发生膀胱癌的危险因素;原发肿瘤数目、分期、有无同发膀胱癌以及术后膀胱癌发生间隔时间对存活率有显著影响.     

Prognostic significance of non-muscle-invasive bladder tumor history in patients with upper urinary tract urothelial carcinoma

ObjectiveTo evaluate the prognostic factors for survival and disease recurrence in patients treated surgically for upper tract urothelial carcinoma (UTUC), focusing especially on the impact of history of non-muscle-invasive bladder cancer.Patients and methodsA single-center series of 221 consecutive patients who were treated surgically for UTUC between January 1999 and December 2010 was evaluated. Patients who had a history of bladder tumor at a higher stage than the upper tract disease, preoperative chemotherapy, or previous contralateral UTUC were excluded. None of the patients included in this study had distant metastasis at diagnosis of UTUC. In total, 183 patients (mean age 66 years, range 36–88) were then available for evaluation. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location (renal pelvis or ureter). All patients were treated with either open radical nephroureterectomy (RNU) or open conservative surgery. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses.ResultsFifty-one patients (28%) had previous carcinoma not invading bladder muscle. Previous history of non-muscle-invasive bladder cancer was significantly associated with tumor multifocality (P < 0.001), concomitant bladder cancer (P < 0.001), higher tumor stage (P = 0.020), and lymphovascular invasion (P = 0.026). Using univariate analyses, history of non-muscle-invasive bladder cancer was significantly associated with an increased risk of both any recurrence (HR = 2.17; P = 0.003) and bladder-only recurrence (HR = 3.17; P = 0.001). Previous carcinoma not invading bladder muscle (HR = 2.58; P = 0.042) was an independent predictor of bladder-only recurrence. Overall 5-year disease recurrence-free (any recurrence and bladder-only recurrence) survival rates were 66.7% and 77%, respectively. Previous history of non-muscle-invasive bladder cancer was not associated with cancer-specific survival. Our results are subject to the inherent biases associated with high-volume tertiary care centers.ConclusionsPatients with previous history of non-muscle-invasive bladder cancer had a higher risk of having multifocal and UTUC with higher tumor stages (pT3 or greater). History of bladder tumor was an independent predictor of bladder cancer recurrence but had no effect on non-bladder recurrence, and cancer-specific survival in patients who underwent surgical treatment of UTUC.     

Metachronous urothelial cancer in bilateral upper urinary tracts and bladder associated with hereditary nonpolyposis colorectal cancer

A 40-year-old man had undergone right hemicolectomy and sigmoidectomy under the diagnosis of ascending and sigmoid colon cancer and right nephroureterectomy under the diagnosis of right ureteral cancer, in 1997 and in 2002, respectively. In 2007, He visited our hospital with a complaint of bloody stool and hematuria. Colon fiberscopy, ureteropelvicscopy and cystoscopy demonstrated colon cancer, left renal pelvis cancer and bladder cancer, respectively, as diagnosed by biopsies, followed by restative colectomy, left nephroureterectomy and cystectomy. The final histopathological examination showed well differentiated adenocarcinoma (pSM) in the colon, and urothelial carcinoma in the left renal pelvis (pT2) and the bladder (pT1). Since his uncle and elder brother had suffered from stomach cancer and colon cancer, respectively, he was diagnosed with hereditary nonpolyposis colorectal cancer (HNPCC : Lynch syndrome). He has been well doing without recurrence for 3 years after the surgery.     

Modified pluck method in en bloc nephroureterectomy with bladder cuff for upper urothelial cancer

AIM: To evaluate the surgical results of the en bloc removal of the kidney and ureter with a bladder cuff by using our modified pluck method. METHODS: We employed this procedure in 28 patients with renal pelvic and ureteral cancer. The clinical stages of the 28 patients were T(1-3)N(0-1)M(0). These patients were operated on by nephrectomy with standard open or retroperitoneoscopic surgery, and then standard or blind dissection of the distal ureter. After simultaneously making a transurethral circular incision of the ureteral meatus with a J-shaped electrode, the ureteral end was plucked out of the bladder, and en bloc removal of the kidney and ureter was performed from the wound. RESULTS: The mean operating time for nephroureterectomy using the pluck method was 278 min in all cases. The mean time for the pluck procedure after nephrectomy was 24 min in 22 cases, and 73 min in six cases where the nephrectomy was carried out via a new lower pararectal wound. There were no intra- or postoperative complications associated with these procedures. Within the mean follow-up period of 25 months, there was no recurrence of tumors in the perivesical retroperitoneal space; however, the usual rate of intravesical recurrence was observed. Three patients died, two of metastatic urothelial cancer and one of heart disease. CONCLUSIONS: En bloc nephroureterectomy using our modified pluck method is a useful procedure for patients with upper urothelial cancer because of the simplicity and ease of the procedure.     

Bladder and upper tract urothelial cancer

PURPOSE: While there are data available indicating the incidence and prevalence of bladder and upper tract urothelial cancer, population level data on resource use, costs and patterns of care for these cancers are limited. We quantified the economic impact of caring for patients with bladder and upper tract urothelial cancer, and determined the primary drivers for such costs in the population in the United States. MATERIALS AND METHODS: The analytical methods used to generate these results have been described previously. RESULTS: An increasing proportion of patients with bladder and upper tract urothelial cancer were being treated in the outpatient setting. Most care was provided by urologists and visit frequency was directly related to disease stage. Only a small proportion of patients potentially eligible for chemotherapy, ie those with advanced disease, sought specialized care from oncologists. Office based diagnostic tests such as cytology were not commonly done, although a substantial number of patients with bladder cancer underwent cystoscopy. The use of excretory urography in these patients was decreasing, while the use of computerized tomography was increasing. Ileal conduits were the most frequently performed type of urinary diversion following cystectomy. The cystectomy rate remained unchanged for a decade. Intravesical therapy was done infrequently in patients with bladder cancer. Annual costs for treating bladder and upper urinary tract cancers were $1 billion and $64 million, respectively, in 2000. These costs represented a $164 million increase over 1994 levels, which outpaced inflation. CONCLUSIONS: The costs of treating bladder cancer increased steadily during a 6-year period despite a decrease in inpatient care. Coupled with a lack of substantial change in transurethral resection and cystectomy rates, this suggests that the primary cost drivers are increased outpatient testing, eg computerized tomography and cystoscopy, and an increase in the number of diagnosed cases. Greater focus on selective use of testing modalities, preventive care such as smoking cessation and earlier identification of patients at risk may help curtail further expenditure with regard to managing bladder and upper urinary tract cancers.     

Uroepithelial tumors of the upper urinary tract following bladder cancer

Five hundred and nineteen patients with primary bladder cancer were treated between January, 1969 and December, 1984, 12 of whom had developed upper urothelial tumors. These patients had received various transurethral treatment for the primary bladder lesions, except for one patient who had undergone total cystectomy and ileal conduit diversion. Overall incidence of patients with upper urinary tract tumors following bladder cancer was 2.3%. The incidence of patients with treated bladder tumors (13.2%) for dye workers was higher than that for the general population (1.1%). The interval between initial treatment of the bladder tumor and diagnosis of the upper tract tumor ranged from 7 to 170 months (mean 70 months). The incidence of upper tract tumors increased with the passage of time. We conclude that the occurrence of upper urinary tract tumors following primary bladder cancers is promoted by nonspecific chemical irritants against the urothelium already made unstable by certain urinary chemical carcinogens.     

Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection

ObjectiveTo identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection.Materials and methodsWe retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods.ResultsThe median age of our cohort was 71 years (interquartile range: 64–78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0–5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non–organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non–organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and≥3 cm, respectively.ConclusionsFollowing RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non–organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.     

Upper tract urothelial tumor after transurethral resection for bladder tumor.

We present a retrospective review of 30 patients who developed upper urinary tract tumors (UUTT) after having been diagnosed and treated for a bladder neoplasm. The mean patient age was 63 years (range 54-72). An average of 4.8 (range 1-10) transurethral resections (TUR) had been performed for bladder cancer prior to the appearance of UUTT. The length of time elapsed between the initial bladder TUR and the subsequent diagnosis of UUTT was variable, with increased incidence in the first 24-72 months (63.3% of the cases). In 21 cases (70%) the bladder tumor was multiple and in 28 (93.3%) the tumor was recurrent. In those patients with unilateral vesicoureteral reflux, an increased incidence of UUTT was found in the refluxing renal unit. In patients with poorly differentiated (grade 3 and grade 2-3) bladder tumors, UUTT was of the similar grade of anaplasia in 75% of cases. These observations, together with those previously published in the literature, allow us to recommend the use of excretory urography (IVP) every 2 years during the first 6 years of follow-up in patients treated for recurrent and/or multiple bladder tumor. Thereafter, follow-up would depend upon the individual clinical situation.     

Association between pioglitazone and urothelial bladder cancer

The U.S. Food and Drug Administration and the European Medicines Agency have recently informed the public of a potential impact of pioglitazone (Actos) use on bladder cancer incidence. These recommendations are based on 2 recent large published cohort studies indicating a possible association between pioglitazone use and bladder cancer development. Currently, there is no urology literature on this subject. We present the current literature reporting the association between pioglitazone and bladder cancer.     

The effect of tumor location on overall survival for pT2–4 bladder and upper tract urothelial carcinoma following radical surgery

IntroductionHistorically, staging and treatment for upper tract urothelial carcinoma were extrapolated from bladder urothelial carcinoma literature. However, embryological, genetic, and anatomical differences exist between them. We sought to explore the relationship between location of urothelial cancer and overall survival (OS).MethodsData was culled from the National Cancer Database from 2004–2015. Patients with pT2–pT4 treated with definitive surgery were included; those with metastatic disease or who received neoadjuvant or adjuvant treatment were excluded. Patients were stratified by tumor location and pathological stage. The primary outcome was OS. Secondary outcomes were predictors of mortality in each pT stage stratum.ResultsA total of 11 330 patients with bladder, 954 patients with ureteral, and 1943 patients with renal pelvis urothelial carcinoma were analyzed. Mean followup was 43.3, 39.4, and 41.4 months for bladder, ureteral, and renal pelvis, respectively. On univariable analysis, ureteral pT2 was associated with worse OS compared to both bladder (61.3 vs. 80.4 months, p=0.007) and renal pelvis (61.3 vs. 80.5 months, p=0.014). Renal pelvis pT3 was associated with improved OS compared to both bladder (42.5 vs. 28.6 months, p=0.003) and ureteral (42.5 vs. 25.7 months, p<0.001). Renal pelvis pT4 had decreased survival compared to bladder (11.4 vs. 17.7 months, p<0.001). On multivariable Cox regression, only renal pelvis pT3 was associated with a 20% decreased risk of mortality compared to bladder pT3 (hazard ratio 0.80, 95% confidence interval 0.72–0.88, p<0.001).ConclusionsRenal pelvis pT3 is associated with lower mortality. Mutational and embryological differences may play a role in this disparity.