Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma.

The aim of this study was to assess patterns of CCND3 gene amplification in bladder cancer and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 102 primary bladder tumor samples in which there was enough tissue material to assess CCND3 gene status by fluorescent in situ hybridization (FISH) was the study group. CCND3 gene FISH amplification present in 31.4 percent of bladder carcinomas, was related to tumor progression (p=0.021) and lower time to progression (mean+-SD; 25.75+-15.25 months) as compared to 33.29+-11.0 months in the CCND3 not amplified group (p=0.05). By immunohistochemistry, Cyclin D3 labeling index was higher in the CCND3 amplified group (mean+-SD, 76.69+-27.51) than in not amplified (mean+-SD, 21.57+-7.02) (p less than 0.0001). The univariate survival analysis showed CCND3 gene amplification to be associated to a shorter progression-free survival (p=0.020) together with WHO histological grade (p=0.001) and pT stage category (p less than 0.0001). Cox’s regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p= 0.030, RR3.561, 95 percent CI 1.128-11.236) together with pT category (p less than 0.0001, RR5.834, 95 percent CI 2.364-14.395). Our FISH analysis suggests that CCND3 gene amplification is a marker of aggressiveness and might be a predictor of tumor progression in bladder urothelial carcinoma.

Multigene methylation analysis of conventional renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common malignancy of the kidney. Since RCC is curable when it is confined to the renal capsule, early diagnosis is extremely important. Promoter hypermethylation is the most common mechanism for the inactivation of the tumor suppressor genes (TSG) in the development of human cancer. This study aimed to investigate the methylation profiles of 7 TSG (RASSF1A, ECAD, TIMP3, APC, MGMT, p16 and RARbeta2) in 3 different tissue samples (normal, premalign, malign) of patients with RCC. Twenty-one patients diagnosed with RCC were included in the study. Methylation-specific polymerase chain reaction was performed to detect the methylation patterns of the 7 TSG. High methylation rates for the genes RASSF1A (76%), p16 (80%), ECAD (42%), TIMP3 (33%) and MGMT (33%) were observed in the patients with RCC. The APC (14%) and RARbeta2 (19%) genes showed low methylation rates. In conclusion, 5 TSG (RASSF1A, ECAD, TIMP3, MGMT and p16) showed high methylation rates in RCC patients. A methylation-based gene test including these genes may be useful in the early detection of RCC.

Quality control of radical prostatectomy: a feasibility study.

The aim of this study was to assess whether the quality of the surgical act could be an important prognostic factor for patients undergoing radical prostatectomy. This study also aims to investigate whether the surgical quality can be assessed by any means. Questionnaires were collected from 23 different institutes including 232 radical prostatectomies (RPr) performed for T1T2 prostate cancer. Blood loss, duration of surgery, margin status, postoperative prostate specific antigen (PSA) and urinary incontinence were analysed and correlated with the yearly number of RPr performed. The mean values obtained for each parameter were very different in the various centres. The outcome in terms of tumour control and incontinence could not be related to a higher or lower number of RPr performed. Quality control of RPr is feasible on the basis of an analysis of a few parameters, such as surgical margins, postoperative PSA and incontinence, that might recognise urologists that perform better or poorer than a proposed average.

Investigation of p53, c-erbB-2, PCNA immunoreactivity, DNA content, AgNOR and apoptosis in bladder carcinoma as prognostic parameters.

The association between known prognostic variables such as TNM stage, histological grade and mutant p53 tumor suppressor gene product, c-erbB-2 oncoprotein, DNA ploidy and cell kinetic data, including mitoses, PCNA expression, AgNOR scores and apoptosis, was investigated in 29 transitional cell carcinoma (TCC) cases. A positive correlation between the histologic grade and all the studied parameters, except for c-erbB-2 expression, and a positive correlation between the stage and histological grade, DNA ploidy, mitoses, apoptosis and p53 expression were found. The results of this study are in accordance with some of the previous studies, except for apoptosis which had been studied for the first time in TCCs. Although we found a statistically significant correlation between the apoptosis and both tumor stage and histological grade, the predictive value of apoptosis as an independent prognostic factor remains to be established in a larger series.

Gemcitabine-induced vasculitis in advanced transitional cell carcinoma of the bladder.

BACKGROUND: Gemcitabine (GEM) is an alternative chemotherapeutic agent for patients with metastatic bladder cancer. It is believed to be a well-balanced agent, having acceptable toxicity and enhanced antitumor activity. The integration of GEM into the initial chemotherapy plan for these patients is still being developed. CASE REPORT: The patient, male, aged 56 years, was suffering from a transitional cell carcinoma of the bladder. Due to frequent local superficial recurrences, radical cystectomy with pelvic lymphadenectomy and continent ileal diversion was performed. Four years after the operation a left inguinal lymphadenopathy was noted and metastatic bladder carcinoma was confirmed on biopsy. Cytotoxic therapy combining GEM and cisplatin and local external irradiation therapy was initiated. The patient developed extensive necrotising vasculitis with muscle damage after the second course of therapy. Chemotherapy was stopped immediately but this was not enough to relieve the symptoms of severe myalgia and swelling, and additional treatment consisting of cyclophosphamide and prednisolone was initiated. CONCLUSION: Although GEM seems to be relatively safe, some unexpected complications may occur during treatment. This case is not common, but it reinforces the need for careful attention to any new symptoms that seem to be unassociated with the primary disease. Prompt evaluation of such symptoms should be carried out in patients receiving GEM therapy.

Significance of serum laminin P1 values in patients with transitional cell carcinoma of the bladder.

OBJECTIVES: The goal of this study was to investigate the relation between serum laminin P1 expression and the grade, stage, size, and multiplicity of the tumors to elucidate the potential role of laminin as a diagnostic and prognostic factor in transitional cell carcinoma (TCC) of the bladder. METHODS: Serum concentration of laminin P1 was measured by radioimmunoassay in 38 patients with TCC of the bladder and compared with the serum laminin P1 values obtained from 34 healthy control subjects. Patients were grouped according to their tumor stage, grade, size, and multiplicity to compare the serum laminin P1 values. RESULTS: The mean serum laminin P1 level in the patient group was statistically higher than the controls (P = 1.3 x 10(-8); with the destruction of basement membrane (stages pT1 or greater), a significant increase in the serum value was observed (P = 0.00023). Laminin level was found to be positively related to the tumor size and number; however, no correlation was observed with the grade. In tumors invading the lamina propria and beyond, the sensitivity of laminin P1 was 78.9% and specificity was 97.1%. The positive and negative predictive values of laminin P1 were 93.7% and 89.5%, respectively. The patients whose serum laminin P1 levels were above the upper limit of normal (1.6863 U/mL) were found to have a higher recurrence rate (72%) than the patients who had lower serum values in the control cystoscopies performed 3 months after the first admission (P < 0.01). CONCLUSIONS: Serum laminin P1 seems to be a valuable adjunctive marker to predict tumor invasion and recurrence. This warrants further research.

Bellini duct (collecting duct) carcinoma of the kidney.

Bellini duct (collecting duct) carcinoma of the kidney is a rare entity often misinterpreted as renal or transitional cell carcinoma on histologic examination. Immunohistochemical identification of specific antigens is needed for the differential diagnoses. We describe a case of Bellini duct carcinoma that arose from the collecting ducts of Bellini and was treated with aggressive surgery and interferon-based immunochemotherapy.

Prostatic carcinoma presenting with painless parotid mass.

Metastasis of prostate cancer to the parotid gland is exceedingly rare, with only 4 cases reported in the literature. We present the case of an 83-year-old white man who had a painless parotid mass that was diagnosed as metastatic prostate cancer. Immunohistochemical staining with prostate-specific antigen was positive. This is the first case of prostate cancer presenting with a painless parotid mass. Prostate cancer can be metastatic to the head and neck region, and this should be kept in mind when treating patients with this disease.

Tubular dysplasia and carcinoma in situ: precursors of renal cell carcinoma.

OBJECTIVES: To identify the dysplastic changes in tubules adjacent to or remote from renal cell carcinoma (RCC) and to assess proliferating cell nuclear antigen (PCNA) expression of normal tubule and carcinoma cells. METHODS: The study analyzed 62 kidneys with RCC that were removed by radical nephrectomy. Pathologic sections were stained with hematoxylin-eosin and evaluated for the presence of dysplasia. Sections that contained dysplasia were then stained by the avidin-biotin immunoperoxidase technique after epitope retrieval for PCNA. RESULTS: Dysplastic changes in normal kidney were identified in 14 cases (23%). Dysplastic changes were adjacent to the tumor in 10 cases. Dysplasia was adjacent to the tumor and diffuse in 6 cases (3 clear cell [CRCC], 2 chromophobe [ChRCC], 1 sarcomatoid RCC [SRCC]), adjacent to the tumor and focal in 4 cases (2 CRCC, 1 papillary RCC, 1 SRCC), remote and focal in 3 cases (1 granular RCC, 1 ChRCC, 1 SRCC), and remote and diffuse in 1 case (CRCC). The lesions represented a focus that could be defined as carcinoma in situ in 3 cases. PCNA immunostaining in dysplastic epithelia was more intense than that in normal tubules and was as intense or even more intense than that in carcinoma cells. CONCLUSIONS: Dysplasia of tubular epithelium is probably a biologic precursor of at least some RCC. Tubular dysplasia warrants further study as an important phase that will provide new insights into the pathogenesis, biologic behavior, and natural history of RCC. Its impact on the surgical management of small unilateral RCC needs to be investigated.

Volume-weighted mean nuclear volume in renal cell carcinoma.

OBJECTIVES: Tumor grade and stage are the most important prognostic parameters for renal cell carcinoma (RCC). The value of histologic nuclear grading, however, is impaired by the inconsistency of pathologists' observations. Estimate of volume-weighted mean nuclear volume (MNV), based on a stereologic method, is correlated with prognosis of bladder, prostate, and endometrial cancer. In this study, we investigated the prognostic value of stereologic estimation of nuclear volume in RCC. METHODS: This study included 62 patients with RCC who underwent radical nephrectomy between 1989 and 1996. Patients were evaluated in two groups: patients with locally advanced and/or metastatic disease were part of the poor prognosis group and patients with localized disease were part of the good prognosis group. Unbiased estimates of MNV were compared with histologic grade, tumor stage, and growth pattern according to Thoenes classification. Group means were compared using the nonparametric Kruskal-Wallis one-way analysis of variance. Univariate analysis of the data was performed for MNV and time to death, metastasis, local recurrence, and disease-free survival by paired sample t test. For categorical variables, Pearson's correlation test was used for statistical analysis. RESULTS: There was no correlation between MNV and patient sex, age, tumor stage, and growth pattern. MNV showed a trend to be higher in sarcomatoid and chromophilic cell types than in chromophobe and clear cell types (P < 0.05). MNV values were significantly higher with increasing grades but no MNV cutoff levels could be defined. The MNV values were not different between localized and locally advanced and/or metastatic disease. CONCLUSIONS: Our results indicate that estimates of MNV are not useful for predicting disease outcome. Further studies are needed to set up reproducible intervals of tumor dedifferentiation that could be carried out in routine practice for predicting progression.

Renal effects of carbon dioxide insufflation in rabbit pneumoretroperitoneum model.

To determine the effects of carbon dioxide insufflation on renal function in a pneumoretroperitoneum model, 24 adult New Zealand rabbits were divided into four groups, six rabbits in each. The first group underwent a 2-hour CO2 insufflation at a pressure of 10 mm Hg in the retroperitoneal space after balloon dissection. In another group, the same procedure was maintained for 4 hours. In the sham-treated groups, the procedure was similarly carried out but without CO2 insufflation. In all four groups, serum and urine creatinine concentrations and renal artery and renal vein blood flow rates were determined separately at the beginning and at the end of the procedure and at 24 hours. Urine output was also recorded at the end of the procedure and at 24 hours. The serum creatinine in the 2- and 4-hour study groups had increased significantly at the end of the procedure, accompanied by a significant decrease in the urine creatinine value. Renal artery and renal vein blood flow rates and urine output were reduced in both groups during the study. All changes in the serum and urine creatinine, renal artery and vein flow rates, and urine output was more pronounced in the 4-hour group. All measures returned to their prestudy values by 24 hours. Pneumoretroperitoneum causes reversible renal dysfunction, which becomes more pronounced with prolonged insufflation. Further research is needed to show the impact of our findings in high-risk patients undergoing retroperitoneoscopic surgery.

Effectiveness of extracorporeal shockwave lithotripsy in the management of stone-bearing horseshoe kidneys.

Although extracorporeal shockwave lithotripsy (SWL) has dramatically changed the management of urinary tract stone disease, the anatomic abnormalities of horseshoe kidneys cause some difficulties in the use of SWL in this disorder. In this study, 18 patients with stone-bearing horseshoe kidneys were investigated retrospectively in order to determine the effectiveness of SWL. Patients received an average of 11,437 + or - 3062 shocks at an average of 18.8 kV with the Siemens Lithostar. Ten patients were treated in the supine position; stones could be localized in the prone position in eight. Catheterization with a double-J stent was the only adjunctive procedure; it was used in four patients prior to SWL. Adequate stone fragmentation (smaller than 5 mm) was achieved in 14 of the 18 patients (78%). Although 5 of them (28%) became stone free within 6 months after the treatment, residual fragments persisted in 9 patients (50%) during the mean follow-up of 55 months. Stones of 4 patients (22%) were not fragmented adequately. We concluded that although adequate fragmentation can be achieved in stone-bearing horseshoe kidneys, the anatomic abnormalities prevent fragment passage in a substantial number of patients.

Vertebral fracture associated with shockwave lithotripsy in a patient with granulomatous spondylitis.

Extracorporeal shockwave lithotripsy (SWL) is an accepted treatment modality in the treatment of urinary stone disease. Many complications have been reported secondary to high-energy shockwaves, but the effects of SWL on the skeletal system have rarely been investigated. We represent the first case of a burst-type vertebral fracture after SWL in an elderly osteoporotic patient with granulomatous spondylitis.

Are obstructing ureteral stones more difficult to treat with extracorporeal electromagnetic shock wave lithotripsy?

In situ extracorporeal shock wave lithotripsy (ESL) has increasingly become accepted for the treatment of ureteral stones. However, treatment success is negatively affected by stone impaction or associated urinary obstruction. In order to assess the impact of obstruction on the outcome of in situ ESL, we reviewed the results in 503 patients treated in this way. The presence and severity of urinary obstruction was defined prior to ESL, being classified as no or mild obstruction (Group I) and moderate or severe obstruction (Group II). The stone-free rate in the nonobstructed group was 90%, whereas it was 85% in the obstructed group (P > 0.005). While all of our patients were treated on an outpatient basis, two patients in Group I and four patients in Group II required hospitalization with the diagnosis of pyelonephritis. All six patients were treated successfully with appropriate measures. No other serious complication occurred that required hospitalization. We conclude that urinary obstruction does not affect stone disintegration or passage and suggest that in situ ESL should be the treatment of choice in ureteral stones.

Effect of extracorporeal shockwave lithotripsy on plasma and urine endothelin concentrations.

Since the first reports of extracorporeal shockwave lithotripsy (SWL), there have been increasing numbers of articles in the literature documenting renal blood flow impairment and blood pressure elevation as complications. However, little is known about the pathophysiology and prevention of these complications. In this prospective study, the influence of high-energy shockwaves on plasma and urine endothelin concentrations was investigated in 20 patients with renal stones. The patients were randomly assigned to receive a calcium channel blocker, 10 mg of nitrendipine (Bypress; Bayer) (N = 10) 2 hours before SWL or no medication (control group; N = 10). Blood samples were taken just before and 1 minute after application of 3000 shocks. Urine samples were collected by ureteral catheters. The plasma endothelin-1 concentrations were significantly elevated after SWL in the control group (P = 0.003). On the other hand, nitrendipine significantly reduced plasma endothelin concentrations after SWL (P = 0.003). No significant change was observed in urine samples and blood pressure measurements. These results suggest that endothelin release after SWL may be a cause for lithotripsy-induced hemodynamic changes. Medical prevention with calcium channel blockers warrants further investigation.

Does respiratory gating improve extracorporeal shockwave lithotripsy results?

The reliability and efficacy of extracorporeal shockwave lithotripsy (SWL) has been established in urinary stone disease. Its combination with respiratory gating might be a useful method to increase the effectiveness of treatment and reduce the number of shocks required. For this purpose, the results of SWL combined with respiratory gating were compared with those of SWL without gating. There was no difference in the stone-free rates of the two groups or in the complication rate. It is concluded that this method neither decreases the number of shockwaves needed nor increases the effectiveness of SWL.

Premalignant lesions in the kidney.

Renal cell carcinoma (RCC) is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN) is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1) morphological similarity; (2) spatial association; (3) development of microinvasive carcinoma; (4) higher frequency, severity, and extent then invasive carcinoma; (5) progression to invasive cancer; and (6) similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

Ureterorenoscopy: a new approach in the diagnosis and treatment of upper urinary tract disorders.

Endoscopy is a well-established method of diagnosing and treating lower urinary tract disorders. Developments in the optical quality and manufacture of more precise instruments now also makes inspection of the upper urinary tract possible. Today, ureteric stones can easily be dealt with by non-operative measures with the use of operating ureterorenoscope. Diagnosis and treatment of other pathological conditions of the upper urinary tract are also possible. It is also the best way of assessing ureteric and renal pelvic tumours.

Relationship of blood groups and transitional cell carcinoma of the bladder.

Blood groups of 50 patients with transitional cell carcinoma of the bladder, who were followed up for a minimum of 3 years, were analyzed. The blood group distribution of the patients reflected that of the general population. There was no relationship between blood groups and stage and grade of the tumour at initial presentation. However, patients with blood group O had worse prognosis than the others.

Carcinoma of the bladder in patients less than 40 years old.

Records of fifteen patients less than 40 years old with carcinoma of the bladder are reviewed. Fourteen patients with transitional cell carcinoma had well or moderately differentiated superficial papillary tumours. One patient with adenocarcinoma died within 4 months with progressive disease. Four patients experienced recurrences and 9 patients had no recurrence of tumour after a mean follow-up of 55 months. It is concluded that the fate of patients younger than 40 years with bladder cancer is not different from those in older age groups.