Synchronous multifocal development of invasive transitional cell carcinoma of the urinary tract in a patient with renal failure receiving long-term hemodialysis: a case report

We report a case of transitional cell carcinoma in a patient with chronic renal failure receiving hemodialysis for 22 years. A 55-year-old man was admitted to our hospital. Under diagnosis of invasive bladder cancer and left renal pelvic tumor, removal of the whole urinary tract, e.g., bilateral nephroureterectomy and total cystourethrectomy was performed. Transitional cell carcinoma was found in bilateral renal pelvis, left ureter, bladder and prostate in the resected specimen. Thirteen months after the operation, multiple lung metastases and pathologic bone fracture of the 4th lumber vertebra were found. Chemotherapy (3 courses of modified CISCA, consisting of cisplatin, adriamycin and cyclophosphamide) was performed, but the died of systemic metastases of cancer and bleeding due to perforation of multiple gastric ulcers.     

Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract

A retrospective analysis of 74 cases of transitional cell carcinoma of the renal pelvis and ureter treated at this institution over the past 30 years is presented. When nephrectomy alone or incomplete nephroureterectomy was performed, subsequent transitional cell carcinoma developed in 30% of the ureteral stumps. Subsequent bladder carcinoma occurred in 25% of the patients with primary upper urinary tract carcinoma. The type of initial surgery performed did not appear to influence this incidence of subsequent bladder tumors. Contralateral upper urinary tract carcinoma developed in only one patient. When nephroureterectomy is performed for carcinoma of the renal pelvis and ureter, a cuff of bladder that includes the ureteral orifice should be removed to obviate recurrent disease in the ureteral stump. Since single-incision nephroureterectomy did not include the intramural ureter in 50% of the cases in which it was performed, a second incision may be required for adequate exposure.     

Transitional cell bladder carcinoma in patients younger than 40 years of age

OBJECTIVE: The clinical and pathological characteristics of bladder cancer in young patients were analyzed to determine if patients with bladder cancer under the age of 30 have a better prognosis than older adults and if transitional cell carcinoma of the bladder in patients aged 30 to 40 years has a similar behaviour to that observed in the higher risk population. METHODS: A retrospective review of transitional cell carcinoma of the bladder in patients less than 40 years old that had been treated between January, 1993 to August, 1997 was undertaken. RESULTS: We found 8 patients (5 men and 3 women) with urothelial tumor, accounting for an incidence of 4%. Four cases were diagnosed and staged TaG1, 2 T1G1 and 2 T1G2. Recurrence was observed in one case (12.5%) and progression in none. CONCLUSIONS: Transitional cell carcinoma of the bladder in patients under the age of 40 is usually associated with low grade and low stage tumors. The foregoing finding is certainly observed in those aged less than 30 years old. Bladder cancer is relatively rare in this age group, although we have found a higher incidence than that reported elsewhere. Treatment and follow-up depend on tumor grade and stage, regardless of age.     

Computed tomography for detection and staging of transitional cell carcinoma of the upper urinary tract

A total of 91 patients were treated for upper tract urothelial tumors between 1981 and 1991. Preoperative computed tomography (CT) scans and nephroureterectomy for treatment of transitional cell carcinoma were performed in 26 patients. At pathological examination, 28 tumors were diagnosed of which 19 were in the renal pelvis and 7 were in the ureter. Intravenous pyelogram, retrograde and antegrade pyelogram detected 26 of 28 tumors (93%). CT detected 24 of 28 tumors (86%). However, CT is still the best current method for staging of upper urinary tract urothelial tumors, although staging was correct in only 5 of 9 T3 and T4 tumors.     

Urethral recurrence of bladder cancer 16 years after total cystectomy. A case report]

A 74-year-old man was admitted to our hospital. Diagnosis of invasive bladder cancer was made and a total cystectomy was performed on January, 30, 1980. Histological examination showed transitional cell carcinoma, grade 2, pT1 is N0M0. After 16 years, when he suffered left femur, he had right inguinal lymphnode swelling. On the biopsy of the inguinal mass, histology was transitional cell carcinoma. The urethral washing cytology was positive. Lung CT scan dem onstrated multiple lesions. He was diagnosed of the urethral recurrence, right inguinal lymphnode metastasis and lung metastasis of bladder cancer. This case is the 5th case of urethral recurrence of bladder cancer following cystectomy in our hospital.     

Disseminated intravascular coagulation: pathophysiology and principles of management

OBJECTIVE: To analyze the survival and the main prognostic factors in patients with transitional cell carcinoma of the upper urinary tract. METHODS: From 1983 to 1996, we treated 50 patients with transitional cell carcinoma of the upper urinary tract. Treatment was basically conservative except in those cases whose tumor stage or grade required a radical approach. Grading and staging were performed according to the 1992 TNM classification. Eighteen patients had died at one year mean follow-up., At the time the study was completed (June, 1997), 32 patients were alive with a mean follow-up of 4.9 years. Disease-free survival, overall and specific survival were analyzed according to sex, age, association with bladder tumors, localization, type of treatment, tumor size, number, histological grade and stage. RESULTS: The male-to-female ratio was 5:1. Patient mean age was 65.7 years. Association with bladder tumors was observed in 50%. Treatment was conservative in 40% and radical in 60%. The five- and ten-year disease-free survival rates were 69%, overall survival 61% and specific survival 71%. The univariate analysis showed the following to be unfavorable prognostic factors for survival: renal vs ureteral tumors, radical vs conservative treatment, high grade and stage tumors. The association of carcinoma in situ with other tumors of the upper urinary tract was also found to be an unfavorable factor for disease-free survival. The multivariate analysis associated T4 and G3 tumors with poor prognosis. CONCLUSIONS: Transitional cell carcinoma of the upper urinary tract was associated with bladder tumors in 50% of the cases. Low grade stage tumors demonstrated a high survival rate, therefore conservative treatment should be the first approach. High grade/ stage tumors were found to be unfavorable prognostic factors for survival.     

Urinary bladder transitional cell carcinoma with trophoblastic differentiation

Transitional cell carcinoma (TCC) with trophoblastic differentiation (TD) is a newly recognized variant of urothelial cancer which produces placental proteins, predominantly beta-human chorionic gonadotropin (HCG). It has a poor prognosis. About 210 cases were described, mostly from North America, Europe and Japan. This is the first report of TCC TD in a resident of Israel's upper Galilee. A 69-year-old man whose urinary papillary bladder tumor was established cystoscopically, refused treatment and stopped follow-up. 3.5 years after his last visit, he returned and cytologic examination revealed malignant urothelial cells, while intravenous pyelography disclosed a urinary bladder defect. Cystoscopy showed numerous papillary masses dispersed over the bladder mucosa, which were resected transurethrally. Histopathologic examination revealed TCC grade III, stage A. Tumor cells were immunopositive for beta-HCG and human placental lactogen. 4 transurethral resections of large masses were performed within 2 months. Pulmonary metastases developed and the patient died 4 years after the detection of the urinary bladder tumor.     

Multiple cutaneous metastases as the first sign of lung cancer in a patient with well-differentiated papillary transitional cell carcinoma of the urinary bladder

A case of multiple, cutaneous metastases as the first sign of lung cancer in a patient with well-differentiated, papillary, transitional cell carcinoma of the urinary bladder is presented. In the left clavicular region were two, sharply demarcated, dark red tumors measuring 3 and 2 cm in diameter with a history of rapid growth and intermittent spontaneous bleeding. Thorough examination of the patient revealed 16 additional skin lesions, which were dark red macules and papules, 2-3 mm in diameter, situated on the left side of the chest. The skin biopsy material (tumors, macular and papular lesions) was studied using histological and immunohistochemical techniques and showed intact epidermis and massive dermal and subcutaneous metastatic involvement by a small cell carcinoma with neuroendocrine differentiation most likely originating in the lung.     

Transitional cell carcinoma of the distal portion of ureter protruding into the sigmoid conduit six years after cystoprostatectomy

Bladder tumors develop after the diagnosis of upper urinary tract carcinoma in approximately 20% of cases, whereas the incidence of upper urinary tract tumor after the diagnosis of bladder cancer is low, approximately 2%. In a 64-year-old man who had undergone cystoprostatectomy treatment of bladder carcinoma 6 years previously, with the sigmoid conduit used for supravesicle diversion, a transitional cell carcinoma that developed in the conduit was not revealed with intravenous pyelography at regular follow-up intervals. The patient had only hematuria. After an obstructed left kidney, left ureteral stricture, and a filling defect in the conduit were observed radiologically and biopsy revealed a transitional cell carcinoma at the ureterosigmoid junction, the patient underwent left nephroureterectomy, partial resection of a third of the sigmoid conduit, and right ureteral reimplantation. The occurrence of upper urinary tract carcinoma after treatment of bladder cancer should be considered even in light of intravenous pyelography that shows no abnormality; and when such carcinomas occur in this situation, disease involving the conduit should be ruled out.     

Expression of the multidrug resistance-associated protein (MRP) gene in urothelial carcinomas

The intrinsic or acquired resistance of urothelial cancer to chemotherapy is one major obstacle to successful treatment. Generally, the expression level of P-glycoprotein in urothelial cancer is low, so we accordingly investigated the expression of multidrug resistance-associated protein (MRP). We examined the expression of MRP mRNA by means of slot-blotting samples of 11 renal pelvic and/or ureteral tumors, 33 bladder tumors, one lung metastasis from a ureter tumor, 7 non-cancerous urothelia from patients with transitional-cell carcinoma (TCC) and one urothelium from a patient with renal-cell carcinoma (RCC). We also estimated, by Southern blotting, whether or not the MRP gene was amplified in clinical specimens that overexpressed MRP mRNA. MRP was detected immunohistochemically using a polyclonal antibody against MRP. In all, 5 of 11 renal pelvic and/or ureter tumors (45.5%), 17 of 33 bladder tumors (51.5%) and 4 of 7 non-cancerous urothelia of TCC patients (57.1%) expressed more than 2-fold the MRP mRNA levels of drug-sensitive human KB cells. There was no significant difference in the MRP mRNA level between primary and recurrent tumors. Low-grade urothelial carcinomas (G1 and G2 TCCs) expressed significantly higher levels of MRP mRNA than the high-grade G3 TCC. The MRP gene was not amplified in urothelial carcinomas, irrespective of their expression levels of MRP mRNA. Immunohistochemically, MRP was located mainly on the plasma membrane, but also detected on the cytoplasm of cancer cells. MRP may be one mechanism responsible for intrinsic drug resistance in low-grade urothelial cancer.     

Effects of nimodipine and isradipine on endothelin-1-induced contraction of pregnant rat myometrium

Bladder malignancy in the renal transplant recipient is an infrequent occurrence. The 11 previously reported cases reflect an aggressive tumor growth with invasion, requiring partial or complete cystectomy with or without conduit diversion. We report an additional case in a 40-yr-old woman with a living related renal transplant, who experienced rapid progression of her tumor over 3 wk from initial hematuria to a pelvic mass involving the anterior bladder. Her allograft ureter and native ureters, as well as her left iliac vein, became obstructed with tumor in another 2 wk. Biopsy showed poorly differentiated, invasive transitional carcinoma. Attempted resection was abandoned because of finding tumor involvement in most of the pelvis. Chemotherapy was not attempted. She died 2 wk after her attempted resection from tumor burden. Our report presents a collective review of these previously reported 11 cases plus our case. These bladder tumors demonstrate a rapid progression of invasive disease and respond poorly to chemotherapy. There is a possible association of bladder tumors with cyclophosphamide immunosuppression. An aggressive surgical approach should be followed, especially since these tumors present in a younger age group.     

Bladder cancer associated with von Recklinghausen's disease: a case report

A 53-year-old man was admitted to our hospital with urinary frequency and miction pain. He had von Recklinghausen's disease with multiple café-au-lait spots and neurofibromatosis. Computed tomography scan and magnetic resonance imaging revealed an invasive bladder tumor 10 cm in diameter, and not metastasis. He was diagnosed as having a bladder tumor (T3a N0 M0 with von Recklinghausen's disease. After balloon occluded arterial infusion (BOAI) chemotherapy, total cystectomy was performed. Pathological diagnosis was transitional cell carcinoma, G3, pT3aN0M0. We reviewed and discussed 97 cases of carcinoma associated with von Recklinghausen's disease reported in the Japanese literature. Only 5 cases of bladder cancer have been reported, including the present case.     

Conservative therapy for stage T1b, grade 3 transitional cell carcinoma of the bladder

OBJECTIVES: To retrospectively evaluate the usefulness of transurethral resection of bladder tumor (TURBT) and intravesical instillation for pT1bG3 transitional cell carcinoma of the urinary bladder. METHODS: Between May 1984 and May 1997, 45 patients with pT1bG3 transitional cell carcinoma of the urinary bladder underwent TURBT and intravesical instillation with bacillus Calmette-Guerin (BCG) or other anticancer agents. Random biopsy was carried out in 37 patients. The recurrence-free survival rate was determined by tumor size, number of tumors, lymphovascular invasion, and drugs used for intravesical instillation. The median follow-up period was 63 months (range 4 to 145) after the initial TURBT. RESULTS: Of 37 patients who underwent random biopsy, concomitant carcinoma in situ was detected in 18 patients (48.6%). The incidence of concomitant CIS was significantly higher in patients with multiple tumors (P = 0.029). Vesical recurrence was noted in 16 patients (35.6%). The overall 1-, 3-, and 5-year recurrence-free survival rates were 88.5%, 66.7%, and 66.7%, respectively. Progression (muscular invasion) occurred in only 2 patients (4.4%). Total cystectomy was performed in 4 patients, including the 2 patients with progressive disease, and 2 patients with recurrent CIS that resisted BCG therapy. None of the patients died of bladder cancer. CONCLUSIONS: Our results suggest that aggressive attempts at initial or subsequent TURBT combined with BCG therapy achieved good control of pT1bG3 transitional cell carcinoma of the urinary bladder.     

TNM classification for urological cancer

The 5th edition of the new TNM classification for urological cancer has been published by UICC in 1997. Herein, the classification of 4 urological carcinomas (kidney, urinary bladder, renal pelvis and ureter, and urethra) is presented and discussed in comparison with the latest revisions in 1987 and 1992. In the 5th edition, the main revised points are as follows: As for kidney, the primary tumor cut off between T1 and T2 was changed from 2.5 cm to 7.0 cm, and the N classification was simplified as for urinary bladder, all muscle invasive tumors (T2 or T3a in the 1992 classification) are included in the T2 category, which is then subdivided into T2a and T2b; in the urethra, new T categories on transitional cell carcinoma of the prostate and prostatic urethra have been added, and the N classification is simplified; there is no change in the classification for the renal pelvis and ureter. According to these changes, a new system of stage grouping is proposed. There may still be widespread disagreement over the appropriateness of some of the changes introduced in the 5th edition of 1997. It is essential to continue efforts to improve the accuracy of determining the clinical extent of malignant tumors, and to work together in order to achieve our objectives for a unified system of TNM classification.     

Does p53 immunostaining improve diagnostic accuracy in urine cytology?

The frequent change of the transitional cell carcinoma of the urinary tract accounts for the fact that cytological abnormalities in urinary specimens are often not sufficient to enable a definitive diagnosis of malignancy. The purpose of this work was to evaluate the possible use of p53 protein in increasing the diagnostic accuracy of urinary cytology. The expression of p53 was investigated by immunocytochemistry in two groups of urinary specimens, one cytologically positive and the other cytologically negative for cancer. Immunostaining was carried out using a monoclonal antibody to p53. In the positive group, in which bladder cancer was confirmed by cystoscopy and biopsy (31 cases), positive reaction for p53 was found in 55% of the cases (17 cases). In the negative group (92 cases), presence of cancer was histologically ascertained in 64 cases and in this group 15 cases (23.4%) showed positive p53 staining. In the remaining 28 cases of this group, where TCC was not present, 7 cases showed p53 positivity in non-neoplastic urothelial cells. This result shows that, while immunocytochemical detection of p53 in urinary specimens may be used for prognostic evaluation of patients with bladder cancer, it does not contribute to the diagnostic accuracy in cases with morphologically inconclusive or negative cytology. The sensitivity and specificity of the method in detecting bladder carcinoma were 23.5 and 75%, respectively.     

Regulation of ion channel expression by cytoplasmic subunits

The present phase II trial was undertaken to assess the efficacy and toxicity of a combination of paclitaxel and carboplatin as first-line chemotherapy in patients with metastatic transitional cell carcinoma of the urothelium. Twenty patients (age range 50-79 years; inclusion criteria: WHO performance status 0-2, no previous cytotoxic treatment) with metastatic transitional cell carcinoma of the urothelium were recruited and received cytotoxic treatment with paclitaxel at a dosage of 175 mg m(-2) administered over a 3-h infusion and carboplatin given at an AUC of 5 mg ml(-1) min (according to creatinine clearance) administered every 21 days. A total of 65% of patients achieved remissions (CR+PR), with CR occurring in 40% of patients. A further 15% of patients experienced stable disease. Remissions occurred after 2.4 +/- 0.8 (mean +/- standard deviation; range two to four) treatment cycles. The mean duration of responses (CR+PR) was 8.5 +/- 5.5 months. After a mean observation period of 11.4 +/- 4.8 months, 16 patients (80%) are alive. Toxicity included alopecia of WHO grade 3 in all patients, leucopenia of WHO grades 1 and 2 in ten patients, grade 3 in eight and grade 4 in two patients and, finally, severe thrombocytopenia grade 3 in only three patients. Non-haematological toxicity consisted of polyneuropathy of WHO grade 1 in 13 patients and grade 2 in five patients. We thus conclude that a combination of paclitaxel and carboplatin at the given dosage and schedule constitutes an active, well-tolerated first-line cytotoxic treatment for patients with metastatic urothelial cancer.     

In memoriam: Widukind Lenz, 1919-1995

To determine whether microsatellite instability is involved in the development of transitional cell carcinoma (TCC) of the urinary tract, a microsatellite instability assay was carried out using PCR with 9 microsatellite loci. Thirty-eight TCC samples (30 patients with bladder cancer, 5 with renal pelvic tumors and 3 with ureteral tumors) and 1 lymph node with metastasis were examined. Microsatellite instability was found in 8 of 38 tumors examined, and 3 showed alterations in more than 2 microsatellite loci. All 8 tumors were beyond grade 2 and stage pT2 advanced tumors. Stages pT1-2 and pT3-4 patients differed significantly. Microsatellite instability was greater in smokers than non-smokers, but the differences were not significant. Microsatellite instability in TCC of the urinary tract is rare in superficial tumors but more common in invasive tumors. Microsatellite alterations would thus appear to occur, and possibly be importantly involved, in the tumorigenesis of urinary tract TCC.     

Complicated urinary tract infection: analysis of 179 patients

BACKGROUND: The aim of our study was to investigate the incidence, bacteriology, management and outcome of complicated urinary tract infections (UTIs) at the Veterans General Hospital-Taipei. METHODS: Between June, 1993, and July, 1994, medical records of 2,566 patients admitted to the Division of Urology, Veterans General Hospital-Taipei, were retrospectively reviewed. Of these patient, 1,322 had a diagnosis of benign prostatic hyperplasia (BPH), 607 were admitted for renal stones, 496 for ureteral stones, 75 for transitional cell carcinoma (TCC) of the urinary bladder, 47 for renal tumors and 19 for TCC of the ureter. Among all patients studied, 179 (6.98%) acquired a complicated UTI. Of these, 81 were admitted for BPH, 46 for renal stones, 42 for ureteral stones, five for TCC of the urinary bladder, three for renal tumors and two for TCC of the ureter. RESULTS: Of the 179 patients with complicated UTIs, 155 were men and 24 were women. The urine culture positive rate was 76.0% (136/179) and the most common bacteria were Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa. The principle mode of treatment included parenteral antibiotics and urinary diversion (percutaneous nephrostomy and Foley catheterization), when necessary. The infection control rate for these complicated UTIs was 96.3% for BPH, 95.5% for renal stone, 97.6% for ureteral stone, 80% for TCC of the urinary bladder, 100% for renal tumor and 100% for TCC of the ureter. Mortality due to complicated UTI was 3.9% (7/179). CONCLUSIONS: We concluded that the prognosis of complicated UTI is good if diagnosis and appropriate treatment are given promptly. Early drainage to relieve obstruction and intravenous antibiotics are initially necessary. Surgical intervention is required to resolve functional or structural abnormalities after the UTI has been controlled.     

The promoting effect of tumour necrosis factor alpha in radiation-induced cell transformation

The aim of this study was to evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite, in the treatment of advanced transitional cell carcinoma of the urinary tract. 35 patients with unresectable or metastatic transitional cell carcinoma of the urinary tract previously treated with a platinum-based regimen were studied. Gemcitabine was administered at a dosage of 1200 mg/m2 as a 30-min intravenous infusion on days 1, 8 and 15, repeated every 28 days. 31 patients were evaluable for efficacy. 4 patients achieved a complete response (12.9%), 3 a partial response (9.6%) and 13 (42%) were stable for at least 4 weeks (overall response 22.5%; 95% confidence interval 8-37%). The median response duration was 11.8 months (range 3.6-17.7 + months) and median survival for all patients entered was 5 months (range 2-21 + months). 2 patients with complete response are still alive with no evidence of disease after 14 and 21 months. Gemcitabine also provided subjective symptomatic relief from pain, cystitis, dysuria, haematuria and peripheral oedema. Patients experienced little WHO grade 3-4 toxicity, with anaemia in 8 patients (23%), thrombocytopenia in 5 (14.2%), leucopenia in 4 (11.4%) and neutropenia in 7 (20%). WHO grade 3-4 hepatic toxicity occurred in 4 patients (11.4%) and transient elevations of transaminase was noted in 3 (8.6%). No patient had WHO grade 3-4 elevation of serum creatinine level. There was no WHO grade 4 symptomatic toxicity and no alopecia was noted. Transient influenza symptoms with gemcitabine occurred in 18 patients (51.4%) with 13 patients (37.1%) experiencing fever (2.9% WHO grade 3). In conclusion, gemcitabine is an new active agent for the treatment of transitional cell carcinoma of the urinary bladder with a mild toxicity profile; it warrants further investigation in combination with cisplatin in chemotherapy naive patients.