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.

[Update on epidemiology and risk factors of prostate cancer].

Prostate cancer is one of the most common malignancies in the world; more and more men are being diagnosed with prostate cancer worldwide. According to epidemiological studies, prostate cancer will become the most common male cancer by 2010, with 900,000 cases per year. Nevertheless, although the constant increase in incidence, knowledge about the aetiology and risk factors of this tumour is still poor. Several important issues could foster the understanding and prevention of this disease, such as the variation in incidence of prostate cancer between ethnic populations, studies on migrants, dietary and genetic factors. Here we provide an update on epidemiology and risk factors of prostate cancer.

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.

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.

[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.

Clear cell sarcoma of the kidney with invasion of the inferior vena cava.

OBJECTIVE: We present a case of clear cell sarcoma of the kidney (CCSK) in 53-year-old white man who was treated with surgery. This case represents the oldest patient with CCSK published in the English literature. METHODS: Right radical nephrectomy with lymphadenectomy and thrombectomy was performed. RESULTS: Histological findings indicated a CCSK. Tumor cells showed positive vimentin staining. CONCLUSION: CCSK is considered a rare and highly malignant renal tumor. The malignant nature may relate not only to the biological features of these tumor cells, but also to the high resistance against radiation and chemotherapy. The treatment of CCSK has been a subject of controversy.

Opsoclonus-myoclonus syndrome as a paraneoplastic manifestation of renal cell carcinoma. a case report and review of the literature.

Opsoclonus is a rare but distinctive disorder of ocular motility, characterized by irregular, continual and conjugated chaotic saccades of the eyes. It is increased with eye closure and fixation, and it persists during sleep. Opsoclonus appears more commonly in children and in half of such cases in association with neuroblastoma. In adults the most frequent causes are idiopathic (50%) and paraneoplastic (20%). Among the second group, different types of tumors involving a wide variety of organs have been reported. Opsoclonus when accompanied by other symptoms of central nervous system involvement (head, appendicular myoclonus and truncal ataxia) constitutes a clinical picture, known as opsoclonus-myoclonus syndrome. We report the case of a young patient affected by renal cell carcinoma associated with opsoclonus-myoclonus syndrome which did not respond to medical therapy but dramatically improved after cancer ablation.

[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.

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.

The genetic alterations in the oncogenic pathway of transitional cell carcinoma of the bladder and its prognostic value.

This review focuses on the main oncogenes studied in transitional cell carcinoma (TCC) in order to describe their mechanisms of action and investigate their possible prognostic value. Each oncogene family is reported following the order through which the proliferative signal is transduced from the extracellular space via a growth factor to the nucleus where transcription factors are switched on. Oncogenic activation at any level of the pathway will cause an increased transcription of genes enhancing the cell cycle, and proliferation will therefore be amplified. The main molecular or immunohistochemical studies from the literature on the aberrant expression of these genes are examined and compared with the aid of tables. Conclusions suggest that, although some may initially appear promising, no oncogene, has thus far been found to have a definite prognostic value superior to conventional grading and staging.

BTA quantitative assay and NMP22 testing compared with urine cytology in the detection of transitional cell carcinoma of the bladder.

PURPOSE: Both BTA TRAK and NMP22 urine concentrations have shown a sensitivity superior to urine cytology in the detection of bladder cancer. We compared these tumor markers with urine cytology performed on 3 consecutive samples and evaluated by an expert cytopathologist. PATIENTS AND METHODS: The investigations were conducted on 94 patients undergoing a diagnostic cystoscopy for a high suspicion of bladder cancer (group 1) and on 102 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy (group 2). Biopsy specimens were obtained also from tumor negative patients. Immunoassays for BTA TRAK and NMP22 were carried out according to standard methods. The choice of the cut-off was based on the ground of sensitivity and specificity curves intersection. Urine cytology results were expressed as positive, negative and 'dubious'. RESULTS: Overall sensitivity was 56% for NMP22 (cut-off 11 U/ml) and 57% for BTA TRAK (cut-off 60 U/ml). When dubious results were considered as positive cases, urine cytology achieved a sensitivity of 73.3%. Assuming dubious cases as negative results, urine cytology sensitivity resulted 59.3%. When the 2 groups of patients were evaluated separately with different cut-off, there was no significant gain in sensitivity for BTA TRAK and NMP22 over urine cytology. CONCLUSIONS: Urine cytology performed on 3 samples showed the highest sensitivity and specificity. The diagnostic advantage of urine cytology over BTA TRAK and NMP22 was maintained when patients were stratified by tumor grade.

Bladder pheochromocytoma: a 3-year follow-up after transurethral resection (TURB).

We report a case of a 75-year-old female with pheochromocytoma of the bladder. Clinical evaluation included ultrasonography, intravenous pyelography, CT scan, I-MIBG scintiscan. A transurethral resection was performed for a exophytic tumor of 2 cm diameter. The histological result indicated the diagnosis of bladder pheochromocytoma. Three years later the patient remains disease free. Preoperative diagnosis is established by determination of blood and urine levels of catecholamines and their metabolites is a nonspecific diagnostic tool. The sensitivity of CT scan is 82%. Iodine-methyliodobenzylguanidine (I-MIBG), used by scintiscanning, specifically accumulates in pheochromocytomas. Life-long follow-up is necessary to diagnose late recurrences.

Evaluation of P53 protein overexpression, Ki67 proliferative activity and mitotic index as markers of tumour recurrence in superficial transitional cell carcinoma of the bladder.

OBJECTIVES: To confirm the interrelationship between p53, ki67, mitotic index with others known prognostic factors such us stage, grade, multifocality, tumour size, history of recurrence in transitional cell carcinoma (TCC) of the bladder and to determine the prognostic impact of p53, Ki67 and mitotic index in predicting recurrence in superficial bladder cancer. METHODS: Two hundred and fourteen patients with apparently superficial TCC of the bladder underwent TURBT and the 192 histologically Ta-T1 were divided into 104 primary lesions (group 1, mean follow-up 26 months) and 88 recurrent tumours (group 2, mean follow-up 28 months). Data concerning focality, tumour size, number of recurrences and recurrence-free survival were considered in each patients. All samples were immunohistochemically stained with p53 and Ki67 monoclonal antibodies. Mitotic index (MI) was calculated on haematoxylin and eosin stained sections. RESULTS: Recurrence-free survival was significantly lower in superficial recurrent tumours (group 2) compared with primary tumours (group 1). P53 staining was correlated with grade and stage for both 5 and 20% positivity thresholds. Ki67 and MI were significantly different over strata defined by stage, grade and focality in both patients groups but only Ki67 showed a correlation with p53 status. Recurrence-free survival could not be predicted either by p53 status or MI. A 20% cut-off level of Ki67 staining resulted a good predictor of recurrence in group 1 Ta-T1/G1-G2 tumours (p = 0.03). Only Ki67 and multifocality were found to be independent prognostic factors of recurrence in multivariate analysis. Stratifying Ta-T1/G1-G2 patients according to these variables, Ki67 provided a useful tool to predict early recurrence in monofocal lesions from both groups. CONCLUSIONS: P53 and MI despite a fairly good correlation with traditional prognostic factors in bladder TCC seem to play no role in the prediction of tumoural recurrence. A Ki67 index over 20% predicts those single well-differentiated (Ta-T1/G1-G2) tumours which are likely to recur within one year of treatment.

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.

[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.

[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.