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Background: To identify molecular biomarkers for tumor diagnosis and monitoring of disease progression, several noninvasive tests on liquid biopsy have been proposed for different cancers including those of urogenital origin. Among biomarkers, carbonic anhydrase IX (CAIX) has gained attention as it regulates extracellular pH and induces cytoplasmic alkalization contributing to malignant progression and poor treatment outcome. Works on tissues suggested the potential use of CAIX as a tumor biomarker for urogenital malignancies, but only few studies have been performed on its detection in urine., Scope: The aim of the present study is the measurement of CAIX messenger RNA (mRNA) in urine sediments of patients affected by kidney, prostate, and bladder cancers to evaluate the clinical sensitivity and specificity of the test., Procedures: The quantification of the total CAIX mRNA concentration and of its full-length isoform (CAIX FL) have been performed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on RNA extracted from urine sediments of patients affected by urogenital cancers., Results: Urinary total CAIX mRNA expression resulted to be lower in patients with kidney and prostate cancer in comparison with the control group, but no statistically significant difference could be evidenced for bladder cancer. The evaluation of the relative percentage of FL isoform mRNA (FL%) showed a significant increase of FL% in urine from patients with cancer (median = 70.8%) in comparison with the healthy subjects (median = 2.6%) and this finding was confirmed for each cancer type separately. The comparison among receiver operating characteristic curves for total CAIX mRNA, CAIX FL mRNA, and FL% indicated that FL% shows the best diagnostic performance with 90% sensitivity and 72% specificity. Comparison of the results obtained in urine with those found in the corresponding tissues indicated 80% concordance., Conclusions: The CAIX mRNA expression in urine sediments can be considered a surrogate marker of CAIX expression in tumor tissues of urogenital origin. In particular, the analysis of FL% possesses the best characteristics to be a suitable noninvasive biomarker for urogenital cancer diagnosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the concordance and prognostic role of histologic variants of bladder urothelial carcinoma in transurethral resection of bladder tumor (TURBT) and radical cystectomy (RC) specimens., Methods: Clinicopathologic information available at the time of RC and follow-up data from 4110 RC specimens, collected between January 2000 and December 2009 at 17 tertiary referral centers were retrospectively analyzed and evaluated for the presence or absence of uncommon variants of bladder urothelial carcinoma. The presence or absence of uncommon variants of bladder urothelial carcinoma was evaluated on previous TURBT specimens of patients undergoing RC. Cox regression was used to assess the impact of these parameters on cancer-specific survival, and the Kaplan-Meier test for disease-free survival was plotted for survival estimate., Results: Of 4110 patients, 579 were found to have uncommon variants of bladder urothelial carcinoma at RC (14.1%), whereas 266 (6.4%) at TURBT. A lack of agreement about uncommon variants was observed between TURBT and RC specimens in the entire population (P <.001). The presence of uncommon variants at TURBT was associated with an increased risk of pathologic upstage (hazard ratio, 3.24; confidence interval, 1.19-6.37; P <.003) and significant decrease in cancer-specific survival and recurrence-free survival (P <.001)., Conclusion: Although the concordance of presence of uncommon histologic variants of urothelial bladder carcinoma between TURBT and RC is low, the presence of uncommon histologic variants of urothelial bladder carcinoma at TURBT is associated with a less favorable clinical outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Men with good functional results following radical retropubic prostatectomy (RRP) and requiring radical cystectomy (RC) for subsequent bladder carcinoma seldom receive orthotopic bladder substitution. Four patients aged 62-72 years (median 67 years), who had undergone RRP for prostate cancer of stage pT2bN0M0 Gleason score 6 (n = 1), pT2cN0M0 Gleason score 5 and 6 (n = 2) and pT3bN0M0 Gleason score 7 (n = 1) 27 to 104 months before, developed urothelial bladder carcinoma treated with RC and ileal orthotopic bladder substitution. After radical prostatectomy three were continent and one had grade I stress incontinence, and three achieved intercourse with intracavernous alprostadil injections. Follow-up after RC ranged between 27 and 42 months (median 29 months). At the 24-month follow-up visit after RC daily urinary continence was total (0 pad) in one patient, two used one pad for mild leakage, and one was incontinent following endoscopic incision of anastomotic stricture. One patient died of progression of bladder carcinoma, while the other three are alive without evidence of disease. The three surviving patients continued to have sexual intercourse with intracavernous alprostadil injections. Men with previous RRP have a reasonable chance of maintaining a satisfactory functional outcome following RC and ileal orthotopic bladder substitution., (2014 S. Karger AG, Basel.)

Transitional cell carcinoma of the bladder is a rare entity in childhood. We report on a 9-year-old girl with transitional cell carcinoma of the bladder who presented with gross hematuria. Ultrasonography revealed a papillary lesion in the bladder, and the diagnosis was confirmed by cistoscopy. Complete transurethral resection of the lesion was performed and follow-up with urine cytology, vesical ultrasound and transurethral cystoscopy at 4 years showed no evidence of recurrence.

Objective: In human cancers, carbonic anhydrase IX (CAIX) influences cell proliferation and tumor progression, maintaining intracellular and extracellular pH under hypoxic conditions. An alternative CAIX isoform, lacking of exons 8-9 (AS) and independent from the levels of hypoxia, was recently demonstrated in cancer cells. AS-CAIX competes with the full-length (FL) isoform in the regulation of the extracellular pH, mainly in a mild hypoxic status. In the present study, we evaluated mRNA expression of the 2 CAIX isoforms and their clinical relevance in bladder cancers and urine sediments., Materials and Methods: We measured mRNA expression of FL- and AS-CAIX isoforms in tumor tissues and benign mucosa from 45 patients with bladder transitional cell carcinoma. The expression of the 2 isoforms was also measured in urine sediment of 81 bladder cancer patients and 93 control subjects., Results: Expression of FL-CAIX mRNA was lower than AS-CAIX in benign mucosa (P = 0.006) whereas in paired bladder cancers FL-CAIX mRNA was higher (P = 0.007). Consequently, the percentage of FL-CAIX in bladder cancers [median: 62.6%] was significantly higher than in benign mucosa [15.0%] (P < 0.0001). In the urinary sediments of bladder cancer patients FL-CAIX mRNA was significantly higher in comparison with normal controls (P = 0.003). FL-CAIX percentage appeared dramatically higher in urine sediments of bladder cancer patients [64.5%] in comparison with controls [7.5%] (P < 0.0001). In addition, FL-CAIX% was significantly different in sediments from pTa-pT1 and ≥ pT2 patients [51.5% and 91.7%, respectively] (P = 0.016). Stratification according tumor grade indicated that FL-CAIX% was significantly lower in G1 bladder cancers [33.3%] in comparison with G2-G3 [88.6%] (P = 0.005) The clinical sensitivity for FL-CAIX% in urine sediments was 0.93, with a 0.76 specificity. Using the same cut-off positive predictive value (PPV) was 0.78, whereas negative predictive value (NPV) was 0.93., Conclusions: Our results seem to indicate that in bladder cancers and related urine sediments, FL-CAIX is the prevalent and is the most accurate clinically relevant variant surrogate of hypoxic stress., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Renal transplant recipients with high-risk bladder cancer following cystectomy need a urinary diversion preserving the renal function and possibly maintaining body image, while still offering the best oncological outcome. The aim of this report is to describe our experience of radical cystectomy and orthotopic ileal neobladder with Studer technique in this population, and to review the literature. We performed radical cystectomy and Studer ileal neobladder in four male patients (median age 67 years) after median time of 9.5 years following renal transplantation. Pathology revealed pT1HGN+ transitional cell carcinoma in one case, pT1HGN0 in two and pT3aHGN0 in one. Two patients presenting aggressive disease (N+ and pT3a) died of tumour progression after 20 and 14 months, respectively, while the other two are alive after 56 and 36 months of follow-up with no evidence of disease, stable serum creatinine (2.29 and 1.6 mg/dl) and mild metabolic acidosis. Day and night-time urinary continence were satisfactory in all patients. Good functional outcomes have been reported in the 20 cases of ileal orthotopic neobladder with different techniques published so far and the global experience of 24 cases with a median follow-up of 39 months documents a cancer specific survival of 62.5%., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

Objectives: Urinary hypermethylation of BCL2, hTERT, and DAPK promoters has been previously demonstrated as an accurate biomarker for the detection of urothelial carcinoma of the bladder (UCB) in patients undergoing radical cystectomy. In the present study, we investigated with a validation intent the frequency and levels of methylation of the same 3 genes in tumor tissue and urine sediment of patients undergoing transurethral resection (TUR) for non-muscle-invasive (NMI) UCB., Materials and Methods: A total of 108 consecutive patients with NMI UCB and 105 controls with no genitourinary malignancies were enrolled in this prospective study conducted in 2 tertiary referral academic urological departments with an advanced molecular laboratory. The frequency and levels of methylated BCL2, hTERT, and DAPK promoters were evaluated with quantitative methylation-specific real-time polymerase chain reaction in DNA extracted from tumor tissue and paired normal bladder mucosa retrieved at the time of TUR in patients, and from urine in patients and controls., Results: In tumor tissue, at least 1 gene was hypermethylated in 91% patients (BCL2 in 62%, hTERT in 53%, DAPK in 48%). Methylation of hTERT was significantly correlated with tumor grade (P = 0.026). In urine sediment sensitivity and specificity were 76% and 98%, respectively, using BCL2 and hTERT. The number of methylated genes was highly correlated with tumor grade (P = 0.005). Methylated BCL2 and hTERT in urine sediment were highly correlated with those of the corresponding bladder tumor qualitatively (P < 0.001), and only BCL2 also quantitatively (P = 0.005). Methylation levels of BCL2 and hTERT were variably associated with tumor grade and stage, but were significantly correlated with patient age (P = 0.004 and P = 0.027, respectively)., Conclusions: These findings suggest that quantitative methylation analysis of BCL2 and hTERT, but not DAPK, in urine sediment may be a useful tool in the diagnosis of NMI UCB, deserving future applicability studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the gold standard for high grade and muscle invasive bladder cancer. Although consensus exists on the need for node dissection, its extent and role are still matter of debate. However, an ever-growing body of data supports an extended dissection since it may provide a survival advantage in both node positive and node negative patients without significantly increasing morbidity and mortality. Besides dissection extent, the modality of specimen submission and node retrieval have a key role in the quality of node assessment. Moreover the stage of primary bladder tumor, the total number of lymph nodes removed, the lymph node tumor burden, the extracapsular extension and the lymph node density have been demonstrated to be important prognostic variables in patients undergoing cystectomy with node metastases and could be useful to accurately stratify patient risk in order to identify those who may benefit from adjuvant therapies. Even if evidence from the literature is only based on retrospective studies, an extended dissection at the time of cystectomy appears to provide a more accurate staging and enhance survival; future prospective studies taking into account the new prognostic factors are needed.

The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to initiate appropriate immunosuppressive regimens depending on the tumor type and stage of development. The first case presented is one of a 65-year-old patient with a double genitourinary carcinoma (penis and bladder). The patient received kidney transplantation 7 years prior to this event. After adequate surgical treatment (partial amputation of the penis for squamous cell carcinoma and complete transurethral resection of bladder adenocarcinoma), the patient was noted to be free of tumor recurrence and had functioning renal graft with a 2-year follow-up.

Granular cell tumor of the urinary bladder is an exceedingly rare disease, with only 10 cases reported so far in literature. We report a case of granular cell neoplasm of the bladder incidentally found in a 44-year-old woman during an abdominal ultrasound examination for evaluation of stress urinary incontinence. The patient underwent a transurethral resection of the mass and histological examination revealed the presence of a granular cell tumor. Immunohistochemical staining for neuron-specific enolase and S100 protein was positive. At a 6-month follow-up the patient is free of bladder recurrence.

Background: The enzyme tankyrase-1 (TNKS-1), a member of the growing family of poly(ADP-ribose) polymerases (PARPs), was identified as a component of the human telomeric complex. PARPs catalyze the formation of long chains of poly(ADP-ribose) onto protein acceptors using NAD(+) as a substrate. TNKS-1 interacts with the telomeric DNA-binding protein TTAGGG repeat-binding factor 1 (TRF1), which is a negative regulator of telomere length. TNKS-1 is a positive regulator of telomere elongation and its activity appears to be upregulated in some human cancers., Methods: We evaluated for the first time TNKS-1 mRNA expression by real time RT-PCR in tumor tissue, paired normal mucosa and urine sediment in patients with transitional cell carcinoma (TCC) of the bladder. Samples were collected from 41 consecutive patients, 20 with non-muscle-invasive (pTa-pT1) and 21 with muscle-invasive (>/=pT2) bladder TCC. Results obtained in urine sediment were compared with those from 40 healthy subjects matched for age and sex., Results: In pTa-pT1 tumor tissues, TNKS-1 mRNA levels were significantly higher than in >/=pT2 patients (p<0.0001). In urine sediment from TCC patients, independent of tumor stage, TNKS-1 mRNA levels were significantly higher than in healthy controls, with maximal levels in >/=pT2 patients. In particular, TNKS-1 mRNA levels in urine were elevated in 31/41 patients with a sensitivity of 81% in >/=pT2 tumors and 65% in pTa-pT1 TCC. Of patients with pTa-pT1 tumors, 11 had a recurrence within 18 months after initial transurethral resection. In these patients, urine levels of TNKS-1 mRNA were higher than in non-relapsing patients (p=0.038)., Conclusions: In this preliminary study, TNKS-1 mRNA in urine sediment from patients with bladder TCC correlated with tumor stage, and higher preoperative levels were associated with increased risk of early recurrence.

In case of cystectomy, some forms of urinary diversion can impair the graft function of renal transplant patients. Here we present the case of a 70-year-old male with carcinoma of the bladder 12 years after renal transplantation. Immunosuppression was achieved with Cyclosporin A (200 mg/day) and Prednisone (5 mg/day). The patient's serum creatinine level was 1.4 mg/dl. Following cystectomy, an orthotopic ileal neobladder was constructed by means of Studer technique, and the afferent ileal loop was anastomosed to the graft ureter. Pathology revealed pT1 G3 N+ transitional cell carcinoma. Ten months later, periaortic nodal recurrences necessitated four cycles of chemotherapy with Epidoxorubicyn and Gemcytabine. To date, 20 months after cystectomy, the patient is stable, with day and night-time urinary continence. His serum creatinine level is 1.3 mg/dl, and there is no evidence of hydronephrosis or acidosis. We conclude that the orthotopic ileal neobladder is an effective form of urinary diversion in renal transplant patients requiring cystectomy, allowing good preservation of the renal function.

Background: Nowadays urinary cytology methods in early diagnosis of superficial bladder transitional carcinoma (TCC) allow the identification of about 35-50% of tumors. Cytoscopy and biopsy are reliable but invasive. It has been recently shown that allelic abnormalities detected by microsatellite analysis of DNA extracted from urine sediment can be successfully used in TCC. We performed a comparative study between urinary cytology and microsatellite sequence alterations in patients affected by TCC., Materials and Methods: Fifty-eight patients were recruited for the study. Of these, 45 had cystoscopic diagnosis of TCC, while 7 were without apparent lesions after TUR but presented urinary irritative symptoms after BCG endocavitary administration, and 6 who underwent open surgery for benign prostatic hypertrophy represented the control groups. DNA extraction and PCR analysis were performed by using 13 different primers, while urinary cytology was performed by using an Autocyte Preparation System., Results: Urinary cytology confirmed the presence of TCC in 22% of patients while in 15.5% of them a displastic/inflammatory status was found. Microsatellite analysis allowed the identification of 82% of tumors with a 100% specificity. A high sensitivity was obtained in patients affected by superficial (79%) or G1(80%) tumors., Conclusion: Microsatellite analysis represents a highly sensitive and specific marker in TCC diagnosis and monitoring.

Background: The objective of this study was to evaluate the efficacy and toxicity of gemcitabine plus epirubicin in previously untreated patients with advanced urothelial carcinoma who were not eligible for cisplatin-based regimens., Methods: Patients with advanced urothelial carcinoma and at least one of the following characteristics were eligible: impaired renal function (creatinine clearance < 60 mL per minute), an Eastern Cooperative Oncology Group performance status (PS) >or= 2, and age >or= 75 years. The treatment included epirubicin 70 mg/m(2) as an intravenous bolus on Day 1 and gemcitabine 1000 mg/m(2) over 30 minutes on Days 1 and 8 of a 21-day cycle., Results: Thirty-eight patients entered the study, and a total of 152 cycles were administered, with a median of 4 cycles per patient (range, 1-6 cycles per patient). The following Grade 3-4 hematologic toxicities were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed. Dose intensities of epirubicin and gemcitabine were 19.6 mg/m(2) per week (84%) and 532.2 mg/m(2) per week (80%), respectively. There were 2 complete responses (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%), and 12 patients with progressive disease (31.6%), for an overall response rate of 39.5% (95% confidence interval, 25.1-55.1). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months, respectively. The 1-year survival rate was 38%, and the median PFS and OS were 6.4 months and 16.4 months, respectively, in patients with PS 0-1. Thirty patients were symptomatic: Seventeen patients (56.7%) achieved a complete response, and 5 patients (16.7%) achieved a partial symptomatic response., Conclusions: At the doses given in this study, gemcitabine and epirubicin had a good tolerability profile with interesting activity in patients with advanced urothelial carcinoma who were not fit for cisplatin-based regimens., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10860)

Telomerase activity was found to be elevated using a quantitative assay on snap-frozen protein extracts of exfoliated cells in urine and bladder washings and tumor tissue obtained from a male patient with small cell carcinoma of the bladder. To the best of our knowledge, this is the first demonstration of elevated values of telomerase activity in genitourinary small cell carcinoma and is in keeping with the findings in primary lung locations.

Telomerase activity was measured with a quantitative assay, based on a modification of telomeric repeat amplification protocol method, in bladder cancers and apparently normal mucosa in 33 patients. In the same patients, the enzyme was also measured in exfoliated cells collected both with voided urine and bladder washings. Results obtained in urine were compared with those from 20 healthy subjects. Telomerase activity was present in 31 (94%) bladder cancer tissues and in 23 (72%) apparently normal mucosa samples. However, the levels of enzyme activity were significantly higher in cancer tissues in comparison with normal mucosa (mean +/- SD, 47.3 +/- 23.2 and 14.9 +/- 6.1 ng DNA/microg protein, respectively; P < 0.0001). Telomerase activity in bladder cancer tissues was not related to tumor stage and grade. Enzyme activity was present in 27 urine samples and in 27 (82%) bladder washings collected from cancer patients. We did not find correlation between the activity in urine and washings, and their mean levels were not different (22.2 +/- 10.1 and 20.7 +/- 8.0, respectively). Telomerase activity in bladder cancer tissues was correlated to its activity in urine (r = 0.650, P < 0.001) and in bladder washings (r = 0.410, P < 0.05). Only 2 of 20 urine samples from control subjects were found to express telomerase activity at a very low level. This was the first attempt to correlate telomerase activity in exfoliated cells from urine and bladder washings with the activity in corresponding bladder cancers. According to these results we postulate that telomerase activity in urine sediment reflects the activity in bladder cancers better than bladder washings and, for its easy collection, is to be preferred as diagnostic marker in this tumor.

Purpose: We used competitive PCR to verify retrospectively the prognostic significance of c-erbB-2 oncogene amplification in transitional cell bladder carcinomas as a predictive index of patient survival with a maximum follow-up of nine years, and to investigate the variations of c-erbB-2 amplification during bladder carcinoma recurrence and/or progression from superficial to more invasive states., Materials and Methods: Oncogene amplification was determined by an accurate and sensitive procedure based on competitive PCR. Measurements were performed in DNA extracted from fresh cancers or from formalin-fixed, paraffin-embedded tumor samples., Results: The overall mean incidence of c-erbB-2 oncogene amplification was 26% (24/92), with a significant relationship with tumor grade (p < 0.0001). We did not find any statistical difference in survival probability between subjects with (20%) or without (30%) oncogene amplification. During tumor progression we observed a limited increase of tumors carrying oncogene amplification (2 of 20) whereas the mean degree of amplification was not affected., Conclusions: c-erbB-2 amplification seems to be a genetic event related to the degree of bladder tumor differentiation. However the presence and/or the degree of this genetic alteration do not seem predictive of tumor progression, recurrence and survival probability, at least in patients with advanced transitional cell bladder carcinoma. These data seem to indicate that the amplification of c-erbB-2 in bladder carcinoma could be considered as an epiphenomenon, present in a subset of tumors but apparently not related to the clinical outcome.

A paraganglioma of the urinary bladder in a 60-year-old woman presented with irritative voiding symptoms, without hematuria or hypertension. Sonography revealed a well-limited ovoid mass of the posterior wall, and cystoscopy showed that it was covered by normally appearing mucosa. Treatment consisted of transurethral resection, and the patient has been followed for 2 years without recurrence. Histologically the lesion consisted of small nests of spindle cells with clear to acidophilic cytoplasm; mitotic activity was inconspicuous. Immunohistochemical analyses revealed that the tumor cells were strongly positive for neuron-specific enolase and chromogranin A, and negative for cytokeratin, vimentin, neurofilaments, glial fibrillary acid protein and HMB 45. Sustentacular cells at the periphery of neoplastic cell clusters were positive for S-100 protein.

We present an original application of competitive polymerase chain reaction (PCR) for measuring oncogene amplification in DNA from human tumors by simultaneous PCR amplification of genomic DNA with fixed amounts of an internal standard (competitor DNA). Competitors share the same sequence as the target genes but contain an additional 15- to 20-base-pair insert, which allows resolution of the amplified products after polyacrylamide gel electrophoresis and ethidium bromide staining. The gene copy number is derived from the ratio between the intensities of the bands corresponding to the amplified products. Using this procedure, we measured c-erbB-2 amplification in breast and bladder carcinomas in both fresh tumor tissues and paraffin-embedded tissue samples and assessed the precision, sensitivity, and accuracy of the assay. Competitive PCR is a simple, reliable, and accurate method for the evaluation of c-erbB-2 amplification and is potentially suitable for use in the clinical laboratory.

Since January 1985, orthotopic ileal bladder substitution after radical cystectomy was performed in 64 male patients. The Camey I procedure was performed in 35 patients (group 1) and the Studer procedure in 29 (group 2). Clinical, metabolic and urodynamic evaluation was performed at regular intervals with a mean follow-up of 27 months for group 1 and 13.6 months for group 2. Patients with a Camey I bladder reconstruction presented smaller capacity and higher intraluminal pressure resulting in shorter voiding intervals and a practically uniform presence of enuresis, as opposed to those reconstructed with the Studer procedure. The incidence of ureteral reflux was also higher in group 1. Metabolic studies in both groups revealed a slight metabolic acidosis which was treated with oral alkalinization. It is concluded that detubularization of the terminal ileum creates a more favorable low-pressure reservoir.

The authors report 4 cases inverted papilloma of the urothelium. They describe the clinical, evolutive and pathological aspects of this rare tumor.

The initial tumors of 21 patients who earlier had presented with superficial noninvasive transitional cell carcinoma of the bladder and who subsequently underwent cystectomy for invasive disease were examined by the specific red cell adherence test. Eighteen of 21 initial tumors (85.7%) were antigen negative. The time from initial tumor resection ranged from twelve to 168 months (mean thirty-eight months). Loss of blood group antigens indicated enhanced biologic aggressiveness of tumors. However the interval to invasion is sufficiently variable as to preclude the use of this assay for timing of radical cystectomy.

We report a case of myxoid liposarcoma of the bladder dome. Treatment consisted of partial cystectomy and pelvic lymphadenectomy. The patient had no evidence of recurrence 30 months postoperatively. This is the first reported case of primary bladder localization of liposarcoma.

The specific immune response against the malignant cells was investigated in patients with urinary bladder or larynx cancer. Lymphocytes from lymph nodes that drain the tumor site were tested for their proliferative and cytotoxic capacities against autologous malignant cells isolated from the primary tumor. In no occasion was a proliferative or a cytotoxic response observed. However, when the lymph node cell suspensions were depleted of cells expressing both OKM1 and Leu-7 markers by rosetting with the appropriate mAbs, a proliferative response could be observed. The lymphocytes responded to autologous tumor cells only if IL-2 was added to the cultures. IL-2 alone induced some cell proliferation, which was not, however, comparable to that observed in response to both IL-2 and tumor cells. A panel of allogeneic tumor cells consistently failed to stimulate OKM1-, Leu-7- cells in vitro. Response to autologous tumor cells was not caused by HLA-encoded molecules, as occurs in the autologous mixed lymphocyte reaction, since OKM1-, Leu-7- cells failed to be stimulated by autologous non-T cells. A proliferative response was observed only with cells from lymph nodes that had been classified as invaded by malignant cells according to histopathologic criteria. Cells from noninvaded lymph nodes consistently failed to respond. Cells stimulated with autologous tumor cells could be expanded in short-term lines by continuous addition of IL-2 and malignant cells. One of these lines, which comprised mainly T8+ cells, was stimulated to proliferate only by autologous tumor cells, and its proliferative response was inhibitable by anti-class I and not by anti-class II mAbs. This line showed lytic capacities against autologous malignant targets, while it was inefficient against all of the other allogeneic cells tested. In another set of experiments, the mechanisms whereby exogenous IL-2 had to be added to the cultures to sustain a proliferative response against neoplastic cells were investigated. When cocultured with autologous malignant cells, OKM1-, Leu-7- lymphocytes expressed IL-2 receptors, as could be assessed by anti-Tac fluorescent staining. Under these culture conditions, these cells did not produce IL-2, and no proliferation was observed. Addition of purified IL-1 to the cultures induced IL-2 production and cell proliferation. It is concluded that metastatic lymph nodes contain a T cell population that can be detected in a proliferative assay when both suppressor cells are removed and the appropriate molecular signals are supplied.

Lyophilized human dura was used for augmentation cystoplasty in a woman who had a scarred bladder because of multiple resections and fulgurations of superficial bladder tumors. Thirty months later, two sessile tumors developed from the urothelium regenerated over the dura patch, together with infiltrating recurrences elsewhere in the bladder, and a radical cystectomy was performed. This case supports the concept that implantation of tumor cells is a factor in the recurrence of superficial bladder carcinoma.

The clinical course of 33 male patients presenting with concurrent primary tumors of the bladder and prostate was reviewed. Twenty-four of 33 patients were treated by radical cystoprostatectomy. The remaining 9 patients were treated by more conservative means. Seventy-four per cent of the patients survived five years. A rationale for management of concurrent primary tumors of the bladder and prostate is presented.

We investigated the possibility that variations of the metabolism of xenobiotic compounds might be involved in the process of bladder carcinogenesis, by studying activation reactions (phase I) and detoxification reactions (phase II) of xenobiotic compounds in a group of patients with transitional cell carcinoma of the bladder and in a group of controls hospitalised with other diseases. As an indirect estimate of activating reactions (phase I) we measured cortisol hydroxylation, expressed as the ratio between urinary 6-beta-OH-cortisol and 17-OH-corticosteroids. Cortisol hydroxylation was not increased in the group of patients when compared with controls. The variations of phase II conjugating enzymes were followed indirectly by administering paracetamol and measuring the urinary excretion of its main metabolites over a period of 12 h. The variations in the metabolic conjugation of paracetamol were expressed as a percentage of each metabolite, or of unmodified paracetamol excreted in the urine, or as the ratio between a given metabolite and unmodified paracetamol. The data were analyzed with a logistic regression model, analysing the effects of possible confounding variables such as age, smoking, alcohol, blood nitrogen, blood creatinine, glutamic-pyruvic (SGPT), glutamic-oxalacetic transaminases (SGOT) and percent recovery of paracetamol in the urine. Statistical analysis showed that the excretion of mercapturate derivatives of paracetamol was significantly increased in the group of patients. The levels of glucuronic, sulphate and cysteine metabolites were not varied significantly. Since mercapturate derivatives are formed as a consequence of the formation of short-lived metabolites of paracetamol which react with protein, nucleic acids or glutathione, the increased excretion of mercapturic acid derivatives in cancer patients might be an indication of a higher capability of forming reactive molecular species from xenobiotic compounds. We suggest that this factor might play a role in the induction of bladder cancer.