Proposal of an improved prognostic classification for pT3 renal cell carcinoma.

PURPOSE: The prognostic accuracy of the current TNM 2002 staging system for locally advanced renal cell carcinoma has been questioned. To contribute to the development of a more accurate classification for this stage of disease we assessed the correlation between patterns of invasion in the pT3 category and outcomes in a large multi-institutional series. MATERIALS AND METHODS: Pathological data and clinical followup on 513 pT3 renal cell carcinoma cases treated with radical nephrectomy between 1983 and 2005 at 3 Italian academic centers were retrospectively reviewed. Cause specific survival rates were calculated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Estimated overall 5-year cause specific survival was 50.1% at a median followup of 61.5 months in survivors. The current TNM classification was not a significant outcome prognosticator. Patients with a tumor invading only the perirenal or sinus fat were at lowest risk for death from the disease. Patients at intermediate risk had tumors with invasion of the venous system alone. Simultaneous perirenal fat and sinus fat invasion or perirenal fat and vascular invasion as well as adrenal gland involvement characterized high risk tumors. Low risk tumors could be further divided into 2 groups with different outcomes based on a size cutoff of 7 cm. Our classification was a significant predictor of survival on multivariate analysis as well as M stage, N stage, Fuhrman grade and tumor size. CONCLUSIONS: We confirm that the prognostic usefulness of the current 2002 TNM system for pT3 renal cell carcinoma is limited. We have identified 4 groups of tumors with distinct patterns of invasion and significantly different survival probabilities in this category. Large prospective series are needed to validate these findings.

Enhanced urinary gelatinase activities (matrix metalloproteinases 2 and 9) are associated with early-stage bladder carcinoma: a comparison with clinically used tumor markers.

Matrix metalloproteinases (MMPs) are involved in tumor growth and metastasis, promoting the migration and invasion of cells. In this study, the amount of MMP-2 and MMP-9 activity was measured in urine from superficial bladder carcinoma patients (pTa, pT1) to evaluate their possible diagnostic value. The active and total amount of MMP-2 and MMP-9, respectively, in urine from tumor patients were compared with the levels in urine from age- and gender-matched healthy volunteers. Both MMP-2 and MMP-9 activity levels were significantly enhanced in urine from patients with high invasive cancers (pT2, PT3), whereas in urine from healthy controls no or very low MMP activities were found. More importantly, a substantial number of urine samples from patients with superficial tumors contained elevated MMP-2 and MMP-9 activities, suggesting that enhanced urinary MMP activity levels, indeed, might be indicative for early-stage bladder cancer. Overall, urinary MMP-2 and MMP-9 activity levels were significantly correlated to each other, with some individual exceptions. A comparison between urinary MMP-9 activity and a recently proposed urinary marker for bladder cancer, NMP-22, showed slightly lower numbers of patients with elevated levels for MMP-9. But because MMP-9 and NMP-22 levels were not correlated, enhanced urinary MMP activity might be useful as a marker for superficial bladder carcinoma like, or especially in combination with, other markers.

Carcinogen-DNA adducts in bladder biopsies and urothelial cells: a risk assessment exercise.

We have determined the levels of DNA adducts (using 32P-postlabelling) in the biopsies of 20 bladder cancer patients and in the exfoliated bladder cells of 36 healthy volunteers. The aims of the study were (a) to estimate the concentration of DNA adducts in cancer cases and controls according to the level of smoking; and (b) to investigate whether bladder cancer cases had higher levels of adducts in bladder cells than healthy controls had. A dose-response relationship between smoking levels and adduct levels was present among both cancer cases and controls. Cancer cases and the controls had similar adduct levels for the same level of smoking. According to a risk assessment exercise, adduct levels among heavy smokers were roughly comparable with those found in mice and dogs treated with bladder carcinogens, at doses which induce a 50% lifetime risk of bladder cancer.

Progression from superficial to invasive carcinoma of the bladder: genetic evidence of either clonal heterogeneous events.

Until now, no definitive molecular evidence proving or disproving a true progression from superficial to invasive bladder tumors has been reported. A total of 36 lesions from 6 patients affected by invasive bladder cancer after multiple superficial recurrences were analyzed for loss of heterozygosity on 8 loci of chromosome 9 and 2 loci of chromosome 17. In addition, the clonal composition of the tumors from two female patients was examined using the human androgen receptor assay. Our data suggest that papillary bladder lesions can and sometimes do make a true progression into invasive life-threatening tumors; however, this progression is not an invariable sequence because it was definitely proven in 2 but not confirmed in 3 of the cases we examined.

Bladder tumor antigen assay as compared to voided urine cytology in the diagnosis of bladder cancer.

BACKGROUND: The study was aimed at comparing the diagnostic accuracy of the quantitative bladder tumor antigen (BTA) TRAK immunoassay with exfoliative urine cytology in the detection of primary and recurrent bladder cancer. METHODS: The analysis was carried out on 194 high risk patients undergoing a diagnostic cystoscopy, 279 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy, and 45 healthy controls. Urine cytology was performed by a skilled cytopathologist on three consecutive samples. RESULTS: BTA TRAK values resulted significantly higher in tumor positive cases than in absence of bladder tumor for both groups of patients. Non neoplastic urothelial diseases as well as the absence of mucosal abnormalities were associated with a marked increase in BTA TRAK levels with respect to the control group. Overall sensitivity and specificity was 63 and 63% for BTA TRAK (cut-off 34 U/ml), and 68.3 and 73.4% for urine cytology, respectively. The diagnostic advantage of urine cytology was maintained when patients were stratified by tumor grade. CONCLUSIONS: The clinical performance of the BTA TRAK in the detection of primary or recurrent bladder cancer is acceptable and reproducible as shown by similar results with previous reports, although urine cytology performed on three samples showed the highest sensitivity and specificity.

Serum prostate-specific antigen determination in prostatic carcinoma.

Prostate-specific antigen (PSA) is a tissue-specific glycoprotein identified by Wang in 1979. It is synthesized in the prostate independently of prostatic acid phosphatase (PAP). A total of 199 subjects were divided into four groups: controls aged less than 50 years, controls aged more than 50 years, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. PSA cut-off value was set at 10 ng/ml (mean for the BPH group plus 2 SD). With this cut-off value PSA could not be used as an early predictor of prostatic carcinoma. The association of PSA and PAP in prostatic cancer increases the number of patients with positive biological markers.

Tumor markers (CEA, TPA and CA 19-9) in urine of bladder cancer patients.

This study was carried out to evaluate the usefulness of determining urinary levels of carcinoembryogenic antigen (CEA), tissue-polypeptide antigen (TPA), and gastro-intestinal cancer antigen (Ca19-9) in addition to the usual diagnostic procedures for bladder cancer. Sixty-seven patients with transitional bladder cancer, 40 healthy controls and 20 patients with inflammatory diseases of the urinary tract were considered. All urine samples were obtained from patients with intact renal function and no urinary tract infection. TPA and Ca19-9 urinary levels in patients with G3 bladder tumors were significantly higher than in those with lower graded neoplasms. The sensitivity, specificity, and predictive value of a positive (PV+) or negative (PV-) test and the diagnostic accuracy were also evaluated. Ca19-9 was the best urinary marker for bladder cancer (sensitivity 71.6%, specificity 91.6%, PV+ 90.5%, PV- 74.3%, diagnostic accuracy 81%).

Prostatic duct carcinoma with combined prostatic duct adenocarcinoma and urothelial carcinoma features: report of a case.

We report a unique case of prostatic duct carcinoma (PDC) featuring both prostatic duct adenocarcinoma (PDA) and high-grade urothelial carcinoma (HG-UC). An 84-year-old man presenting with hematuria showed at ultrasonography and cystoscopy a papillary neoplasia located near to the verumontanum. Histopathologic examination of specimens from transurethral resection revealed a tumor originating from large prostatic ducts showing 2 different components: PDA with endometrioid features (main pattern) and HG-UC (minor part). Immunohistochemically, the areas of PDA were positive for prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and androgen receptors (AR), while negative for estrogen (ER) and progesterone receptors (PGR). Prognostic factors evaluation pointed out a low proliferation index (10%) and focal expression of p53 (6%); c-erb-B2 was not overexpressed. The HG-UC areas were negative for all previous markers, while positive for thromobomodulin. The proliferation index was high (60%), and p53 was diffusely expressed (55%). The incidence and significance of PDC with combined features is discussed with reference to literature data.

What's in the pipeline about bladder reconstructive surgery? Some remarks on the state of the art.

The fusion of engineering with cell biology and advances in biomaterials may lead to de novo construction of implantable organs. Engineering of neobladder from autologous urothelial and smooth muscle cells cultured on biocompatible, either synthetic or naturally-derived substrates, is now feasible in preclinical studies and may have clinical applicability in the near future. The development of a bioartificial bladder would warrant the prevention of both the metabolic and neoplastic shortcomings of the intestinal neobladder. Two tissue-engineering techniques for bladder reconstruction have been tested on animals: 1) the in vivo technique involves the use of naturally-derived biomaterials for functional native bladder regeneration 2) the in vitro technique involves the establishment of autologous urothelial and smooth muscle cell culture from the host's urinary tract, after which the cells are seeded on the biodegradable matrix-scaffold to create a composite graft that is implanted into the same host for complete histotectonic regeneration. Waiting for the creation of a complete tissue-engineered bladder with a trigone-shaped base, we suggest, in surgical oncology after radical cystectomy, the realization of conduit or continent pouch using tissue-engineered material.

[Prostate cancer-related metastatic bone disease. Some new acquisitions about pathogenesis an therapeutic approaches]. / Patologia metastatica ossea da carcinoma della prostata. Alcune nuove acquisizioni conoscitive su patogenesi e approcci terapeutici.

Anatomic patterns of blood flow and specific dynamic interactions between prostate cancer cell and bone microenvironment influence the distribution of metastatic deposits. Bone components preferentially bind cancer cell and can facilitate tumor growth in bone; cancer cells, in turn, can release some factors that enhance osteoblastic activity. Recent studies, in animal models, have provided evidences of chemoattractant factors (bone homing factors) and of an enhanced adherence of prostate cancer cells to bone marrow endothelium. Additional data suggest "osteomimetic" pattern of prostate cancer cells after their arrival in bone, particularly by taking an osteoblastic behavior. The presence of the cancer cell in bone results in bone matrix increased turnover. Although prostate cancer is characterized by osteoblastic metastases, bone resorption is a regular feature of this tumor and is a necessary factor for its invasiveness in bone. Current treatment options based on radiotherapy and pharmacotherapy are essentially palliative. The bisphoshonates inhibit osteoclastic bone degradation by several mechanisms. Improved knowledges of the molecular mechanisms in the development of skeletal metastases allow to foresee biologically-based therapeutic strategies.

[Nephrogenic adenoma arising from an urethral diverticulum in a female. Report of a case and review of the literature]. / Adenoma nefrogenico in un diverticolo uretrale femminile. Descrizione di un caso e revisione della letteratura.

Nephrogenic adenoma is a benign epithelial tumour localised at the level of the urothelium and caused by metaplasia of the urothelium following prolonged aggressive stimulation over time, for example trauma or chronic urinary infection. Even a diverticulum, in whatever site it is localised, is subject to an increased risk of neoplastic transformation of the urothelium. It above all affects male subjects, with a male/female ratio of 3:1 over the age of 20, which is inverted in younger subjects. The most frequently affected site is the vescical trigonum in 72% of cases, followed by the pelvic tract of the ureter (19%) and urethra. The majority of patients is asymptomatic or reports aspecific symptoms: the most frequent picture is macroscopic hematuria, owing to the rich vascularisation of the tumour. This is followed by irritative type signs such as pollakiuria, strangury, posturination dripping and sometimes painful tenesmus. Differential diagnosis is necessary for pale cell adenocarcinoma, parauretral cysts and Gartner duct's cysts which may be associated with urethral diverticulum, localised on the bottom, and rarely symptomatic. Diagnosis is based on retrograde urethrography, cystography and endoscopic tests, with biopsy if necessary. NMR provides further details regarding the site, localisation and benign or malignant nature of the lesion. Treatment is surgical: endoscopic (transurethral) if the dimension are limited, or traditional using a suprapubic or transvaginal route if it is associated with diverticulum. Prognosis is discrete and depends on the timeliness with which the factors predisposing metaplasia are eliminated.

[Communication between urologist and pathologist. Proposal for the standardization of histological tests requests for neoplasms]. / La comunicazione tra urologo e patologo. Proposta di standardizzazione delle richieste di esami istologici per neoplasie.

The aim of this work is to propose a new clinical data system which should accompany the histological sample for the histologic diagnosis made by the pathologist. Six different schedules on the most important urological tumours are presented: prostate (needle biopsies and surgical approach), bladder (endoscopic procedure and open surgery), kidney and ureter, testis. In each schedule the urologist provides, in a scheme, the clinical report needed for the pathologist's final diagnosis. A clear explanation of the clinical data and a faster method of filling in the form are the qualifying elements of these schedules.

[Comparison of fluoroquinolones (norfloxacin, enoxacin, ofloxacin) in the therapy of lower urinary tract infections]. / Fluorochinoloni a confronto (norfloxacina, enoxacina, ofloxacina) nella terapia delle infezioni delle basse vie urinarie.

The present study was carried out to assess comparatively the effectiveness and tolerance of norfloxacin, enoxacin and ofloxacin in the treatment and prophylaxis of infections of the low urinary tract in non-hospitalised patients. Thirty patients presenting positive uroculture on clinical evidence of ongoing infection were treated. Doses were 400 mg b.i.d. for norfloxacin, and 300 mg b.i.d. for ofloxacin and enoxacin; duration of treatment was 7 days in treatment. The pathogen was eradicated in 94% of cases at the control carried out after 5 days from the end of treatment; in the follow-up at 20 days, recurrences or reinfections were observed in 30% of the cases, almost all of them consisting of complicated infections. Slight side-effects were observed in 8 patients. No significant differences in effectiveness or tolerance were reported between the 3 quinolones under study which are therefore considered reliable overall for urological treatment. The absence of greater side-effects is related to the restriction of indications and the brevity of the therapeutic cycles.

[Blood and urine determinations of tissue polypeptide antigen in patients with bladder carcinoma]. / Determinazione sierica ed urinaria del Tissue Polypeptide Antigen (TPA) nei pazienti affetti da carcinoma vescicale.

The Tissue Polypeptide Antigen (TPA) is an oncofetal antigen widely used in the diagnosis and follow-up of several urothelial cancers. Its urinary and serum detection is performed by means of RIA technique. We determined urinary and serum TPA in 30 patients with bladder cancer who underwent a transurethral resection. Ten out of 30 patients were correctly diagnosed by serum TPA, 22 by urinary TPA. The ANOVA test showed a statistically significant correlation between grade and urinary TPA between stage and serum TPA. Urinary TPA showed a good sensibility in low grade and moreover in Ta stage carcinoma. Serum TPA increased its performance with higher grade carcinoma and in presence of a muscle infiltration, but it never reached a sufficient sensibility to be considered a bladder cancer marker. In conclusion the simultaneous determination of urinary and serum TPA does not give more information than the urinary determination alone.

[Measurement of skeletal alkaline phosphatase in prostatic carcinoma. Preliminary report]. / Il dosaggio della fosfatasi alcalina scheletrica nel carcinoma prostatico. Rapporto preliminare.

Bone metastases frequently occur in prostate carcinoma. Total body radionuclide scan with diphosphonate methylene labelled with 99Tc is commonly used to diagnose such metastases. However this technique is aspecific and frequently unreliable. In recent years several biological markers dealing with bone metabolism were studied. Serum determination of skeletal alkaline phosphatase (ALP) and moreover of its bone isoenzyme (BAP) could be considered a reliable index of osteoblastic activity. In this preliminary report we analyzed a group of 43 patients affected by prostate carcinoma with or without bone metastases. The American Urological Association (AUA) staging system was adopted. Sixteen patients were D2, bone metastases had been suspected by means of radionuclide bone scan and confirmed by Computerized Tomography and/or aimed X-rays. Tandem R-Ostase by Hybritech was used to measure BAP, normal value is set to 20 micrograms/L. All D2 tumours had pathological BAP values (mean value 87.50 micrograms/l); 1/3 stage A, 5/13 stage B, 5/9 stage C and 0/2 stage D1 patients had pathological findings. One of this patients, stage C, revealed a bone metastase at a later bone scan.

[Biophysical principles of tissue electrovaporization]. / Fondamenti biofisici dell'elettrovaporizzazione dei tessuti.

The principles of electrosurgery are based upon well defined physical grounds, explaining the type and extent of the lesions induced by the electric current. Technological evolution has led to the creation of dedicated equipment, allowing efficient use of electrosurgical cutting and coagulation of tissues, both in open and endoscopic surgery. Electrovaporization is the thermal effect obtained when an alternating high power-high frequency current (300 W, 400-500 kHz) is applied to the tissue using an electrode with particular geometric aspects. The main feature is the presence of higher and lower current density zones. The first induce electrovaporization, whilst the second produce simultaneous hemostatic coagulation of the rims. New effective vaporizing electrodes have been recently introduced into clinical practice. Their use in the endoscopical treatment of bladder outlet obstructions, a stimulating alternative to standard resection or laser applications, is currently under evaluation.

[Renal multifocal carcinoma with adrenal gland metastasis in a patient previously treated with radical nephrectomy: what kind of therapy. Review of the literature]. / Carcinoma renale multifocale con metastasi surrenaliche multiple in paziente già sottoposto a nefrectomia radicale dell'adelfo: quale terapia? Revisione della letteratura.

A case of multiple adrenal metastases due to renal cells carcinoma, associated with a multifocal simultaneous renal cells carcinoma has been observed in a female patient previously submitted to radical contralateral nephrectomy for the same disease. In particular, stress is laid on computerized tomography scan diagnosis and surgical procedure.

[Immunohistochemical determination of antigen 19-9 (CA 19-9) in transitional carcinoma of the bladder]. / Determinazione immunoistochimica dell'antigene 19-9 (CA 19-9) nel carcinoma transizionale della vescica.

Carbohydrate Antigen 19-9 (CA 19-9) histological expression in transitional cell bladder carcinoma (TCBC) was studied by means of immunohistochemistry and its findings compared with those of Tissue Polypeptidic Antigen (TPA) and Carcino Embryonic Antigen (CEA). Twenty-one TCBC of various grade and stage were analyzed by using Avidin-Biotin complex method for CA 19-9 and TPA Peroxidase-Antiperoxidase method for CEA. Grade 3 and pT1, pT2/pT3 carcinomas showed a constant staining for CA 19-9 antigen, grade 2 showed a 50% positive immunoreaction while all grade 1 cases were negative. TPA showed an inverse correlation with well differentiated carcinomas which were better and more extensively stained than anaplastic ones. CEA expression was not correlated either with grade or stage. CA 19-9 could be considered as a dedifferentiation marker in TCBC.

[Large calcifications on double J ureteral endoprosthesis "forgotten" in situ. Report of a clinical case]. / Voluminose calcificazioni su endoprotesi ureterale a doppio J "dimenticata" in situ. Descrizione di un caso clinico.

Ureteral endoprostheses can be complicated by incrustations, sometimes making it impossible to withdraw the stent. A case in which the use of cistolithotripsy and of extracorporeal shock-wave lithotripsy (ESWL) allowed withdrawal of a double J ureteral stent with large incrustations is reported. The stent was placed 3 years before. Epidemiology, aetiology and therapeutic aspects of encrusted ureteral stents are discussed.

[The Sarig test. A simple method to evaluate the inhibitory effect on urinary crystallization of calcium oxalate]. / Il test di Sarig. Un semplice metodo per valutare l'inibizione della cristallizzazione urinaria dell'ossalato di calcio.

In this study, the Authors evaluate a simple test proposed by Sarig for the discrimination of kidney stone-formers, based on the overall urine inhibitory effect. A solution of the tested urine is added with sodium-oxalate and the kinetics of calcium-oxalate precipitation is indirectly followed with ionometric selective measurement of the progressive reduction of free calcium ions. A Discriminating Index may be therefore calculated; higher values are obtained in lithiasic patients in comparison with normal controls.