Urologia Journal

Bladder tumours are generally grouped as superficial or invasive because of their different therapeutical regimens. Superficial tumours still cause uncertainties in choosing the best treatment due to their heterogeneity and different behaviour. In the prevision of these tumours it is important to consider all the factors that could influence the prognosis: tumoral characteristics, grading and staging mistakes, effects of the therapy and immunological response. Moreover it is important for clinical studies to have appropriate end points. Prognostic factors and markers with high predictive value can allow specific treatment for the individual cases to be planned.

Clinical, endoscopic and pathological assessment provides the classical factors of prevision for bladder tumours. The risk of recurrence is different among primary and recurrent tumours. The risk of recurrence for primary tumours is correlated to the number of neoformations at diagnosis and to the cystoscopy at three months. The risk of recurrence for recurrent tumours is correlated to the number of neoformations and the previous recurrence rate. It seems that the number of recurrences doesn't imply a higher risk of progression. The most important endoscopic parameters are: number, shape and size of neoformations, and appearance of the vesical mucosa. The most important pathological parameters are: growth pattern, grade, stage, histologic aspect of the vesical mucosa and invasion of lymphatic vessels. All these parameters are correlated to the risk of tumour progression for groups of patients but they cannot predict the fate of the individual case. The predictive value of these parameters could improve with a critical revision of the definitions of grade and stage.

From 1987 to 1993, 26 patients with superficial urothelial bladder carcinoma pT1G3 were observed consecutively at the Dept. of Urology of Pordenone City Hospital and the Division of Pathology of the Centro di Riferimento Oncologico di Aviano (Italy). All patients were treated with TUR and then with a course of BCG-intravesical instillations. The complete immunoprophylaxis treatment consisted of a weekly instillation of BCG for 6 weeks; then cystoscopy and urinary cytologies or random biopsies were performed. An additional 1-monthly BCG treatment for 3 months was administered to 10 disease-free patients. In 6 cases of pT1G3 recurrences, a new complete cycle of BCG was performed whereas in 10 patients with local progression, defined as muscular infiltration, a cystoprostatectomy or RT therapy was advised. Follow-up examinations, planned every 3 months for 2 years and then every 6 months for 3 years, included cystoscopy and urinary cytologies in 19 patients and cystoscopy with randomized biopsies and washing in the remaining 7 patients. Ten patients were disease-free at a mean of 34 months follow-up (range 13-65 months); 6 patients experienced recurrence at a mean of 7 months follow-up (range 3-40 months) and 10 patients local progression at a mean of 13 months follow-up (range 3-44 months). The morphometric study demonstrated that cases with average nuclear area, in the deepest part of the histological section, more or equal to 40 μm² have a threefold progression rate, compared to cases with average nuclear area less than 40 μm² (p = 0.10). Our results would indicate the possible role of morphometric evaluation of prognostically important parameters, in the clinical management of patients with pT1G3 tumours.

The aim of this work is to try to characterize the prognostic value of DNA flow cytometry in superficial bladder tumours and to try to indicate this investigation in clinical practice. The Authors review results reported in literature and those relative to their experience. Data investigation shows that this test has prognostic significance because it is correlated with the stage and grade of the tumour. The correlation with the clinical development of the tumour is not clear in the Authors’ experience. The Authors think that flow cytometry does not have a precise role in clinical practice.

The use of cytogenetics in the characterization of bladder tumours has made it possible to demonstrate that chromosomal alterations are correlated with stage and grade of the tumour and have a predictive value as regards both tumour recurrences and progression. In the last decade the chromosomes involved in the main aberrations have been identified, and a negative prognostic significance has been suggested for some chromosomal aberrations. The knowledge of cytogenetics has been deepened by the sophisticated methods of molecular genetics, that have discovered many oncogenes and suppressor genes probably involved in the development of bladder tumours. The most characteristic molecular alterations of these tumours are losses of genetic information on chromosomes 9, 11 and 17, as a consequence of deletions and/or mutations. Such alterations probably cause the loss and/or the inactivation of suppressor genes (partly hypothetic still) and could represent important predictive factors of tumour progression.

Molecular biology has made giant strides over the last ten years and provides an immense field of research. The Authors first review the concepts of neoplastic proliferation and transformation of the phenotype, analysing cell constitution and its relations with the intercellular space. The most important moment in molecular research was the identification of the growth factors and consequently the process of transduction of signals from the outside into the cell and the retroinhibiting mechanisms of the same signals. The terms oncogene and antioncogene are defined as well as their most significant expressions.

Although superficial bladder cancer may be considered “benign”, it is still today a many-sided neoplasm with a prognosis that cannot be well-defined with known traditional parameters. Proliferation indices Ki67 and AgNOR associated with the expression of some oncogenes (p53, Rb, c-myc, BCL2, c-erbB-2) in relation to traditional parameters could help in the prognosis definition of individual patients. 111 patients with superficial bladder cancer were studied for this purpose, relating the grade, stage, follow-up and morphotype to the proliferation indices. Significant correlations were found with AgNOR, but only for grade with Ki67. The study of the oncoproteins and their different expression showed that those alterations typical of infiltration are already present in the superficial forms, with a significant correlation between oncogenic alterations and grade and stage of disease (p53, Rb) on the one hand, and above all of disease-free interval and progression (c-erbB-2) on the other. Lastly, assessment of the oncoproteins c-myc and BCL2, oncogenes connected with the programmed cell death mechanism (apoptosis), showed important correlations with the neoplastic progression of disease in relation to the p53 expression and proliferative activity.

Histologic and pathologic findings are the most common and useful prognostic factors in transitional cell cancer of the bladder. Thus, clinicians know their peculiar limits very well. The Authors report the results of a literature review about an oncogenic-derivative protein (p53) and about indices of proliferation Ki 67 and TLI, which are frequently studied in bladder cancer.

The Authors report their experience on the study of urothelial bladder cancer by determining the overexpression of p53, DNA-content by flow-cytometry, Ki 67, TLI and cytofluorimetric S-phase in 81 patients. Ki 67, DNA content and p53 overexpression are statistically related with histologic grade, unlike TLI and S-phase. TLI, overexpression of p53 and Ki 67 are statistically related with stage, whereas ploidy and S-phase do not show any relation with stage. The Authors discuss these findings.

We studied in retrospect 144 patients suffering from blunt trauma of the kidney in order to better define the indications for radiological assessment and surgical treatment. If staging is fundamental, most of ail for high-risk patients, it is our opinion that urography must still be considered the decisive X-ray test to assess the renal parenchyma and the urinary tract of the kidney as well as the integrity of the adelph. In cases with micro hematuria and in absence of shock, ultrasound diagnosis is used in place of urography, whereas computerized tomography of the abdomen must be restricted to the cases of renal autoamputation, urohematic extravasation and suspected intraperitoneal injuries. We adopt conservative treatment for all those injuries to the renal parenchyma which respect the urinary tract, whereas we recommend emergency surgical treatment in those cases involving traumatism of the pedicle or kidney fragmentation. We instead postpone surgical treatment in all other cases, following spontaneous haemostasis of the renal space. We believe that both the rate of death and invalidating consequences from traumatic pathology of the kidney can be significantly reduced where there is qualified pre-hospital assistance and cooperation with a medical facility offering rapid detailed diagnosis and specific medicosurgical treatment.

We report our experience on the treatment of carcinoma in situ (CIS) using intravesical therapy with the Bacillus Calmette-Guerin (BCG). From November 1992 to September 1994, 18 patients received treatment: 6 had associated CIS and 12 secondary CIS. Ploidy of each tumour was determined by flow cytometry. Aneuploidy was found in 12 cases, diploidy in 6 cases. After treatment, a standard bladder mapping was performed: 14 patients showed no evidence of cystoscopic and histological disease and if previously aneuploid, became diploid. 4 patients has recurrent disease after therapy; they were all aneuploid before treatment. One of these showed a persistent aneuploidy, although both voided urinary cytology and histological samples were negative. Six months later, a recurrent CIS was seen at the time of cystoscopy. These results enhance the interest in flow cytometry as a possible predictor of response to BCG in the treatment of CIS.

The Authors describe their diagnostic protocol for hypospadias in childhood, including the evaluation of associated malformations and degree of intersexuality. Treatment usually consists of a single-stage operation, except for perineo-scrotal hypospadias, and must be performed before the child is two years old.

Today there are many types of therapies (medical and surgical) in BPH treatment. The Authors suggest dividing BPH into two components: a dynamic phase and a static phase. On the basis of this, they used an association of finasteride and alfuzosin in short and long-term therapy. Provided the rationale is correct, the results in terms of improved flow and symptomatology score suggest that this is an optimal solution.

The Authors describe their experience in treating 81 patients, suffering from urothelial cell carcinoma, with neo-adjuvant, adjuvant or final MVEC chemotherapy according to stage and localisation. The prospective results would seem to indicate conservative surgery and adjuvant chemotherapy for pT3N0M0G1-2 bladder tumours, prognostic improvement, at least with regard to disease-free period, in pT3N0M0 cancer, the possibility of downstaging in T4N + M + cancer and more clinical remissions in transitional cell carcinoma in the upper urinary tract. Furthermore, the therapy proved to be relatively easy for the “non-oncologist” urologists. Side effects are mentioned.

Giant renal leiomyoma is a rare benign tumour with a prevalently smooth muscular component; its clinical aspect and radiological and histological aspects are described. Renal leiomyoma should always be considered in differential diagnosis of a renal mass and surgical exploration is necessary to obtain the histological evidence.

A nephrogenic bladder adenoma case is reported in a 64-year-old man with urinary tbc. This association has never been reported in literature. From the pathogenetic point of view, it can be included in Mostofi's hypothesis, which considers chronic phlogosis as the input for urothelial metaplasia.

The Authors describe the clinical case of a patient with Reifenstein's syndrome who presented other diseases (breast cancer, Berger's syndrome, renal insufficiency). For the treatment they utilised a scrotal tubular flap prepared in another hospital 15 years before.

The Authors report a case of renal liposarcoma 1.5 cm in diameter, found in a 45-year-old woman with a normal contralateral kidney. Since diagnosis was not completely clear after preoperative imaging-studies, like intravenous pyeloureterography, computed tomography and selective arteriography, an open biopsy was performed after the renal vessels were clamped: the intraoperative frozen-section report was benign lipomathoid lesion and an enucleo-resection was performed. The final pathological findings were of a well-differentiated renal liposarcoma with typical lipoblastic cell. Diagnosis and treatment are briefly discussed with reference to recent literature.

The importance of early diagnosis is by now accepted. As urological pathologies predominantly involve men, it is natural for the urologist to seek co-operation regarding primary and secondary prevention with the Medical Corps. Paediatricians and family doctors are the other professional figures who play a fundamental role in this field. The records are given of the congress “Prevention and early diagnosis of urological diseases” between the Military Corps and the National Health Service, held at Belluno in June 1994.

In this paper, the Author indicates the incidence of urogenital pathologies in conscripts at the moment of the selective visit, which involves two categories of military personnel: a) personnel for compulsory enlistment, b) personnel for volontary enlistment, each with its own juridic state and different criteria of assessment. The task of military legal medicine is not only to select generally suitable individuals, but also those in good health at the beginning of the service and who must remain so in relation to the specific job. During these selective visits a considerable number of cases have been found in particular of pathologies involving the urogenital system. The Author examines the list of illnesses and imperfections and in particular those pertaining to section 29 and 35 regarding pathologies of urogenital system. The study was carried out on a sample of young men doing their National Service in the six-year period from ‘88-'93, who were visited in the hospitals of Verona, Padua and Udine.

The Medical Corps is a privileged observatory of the various pathologies found in youths. This is even more evident in the case of a Military Hospital like that in Padua, which serves the north-east regions of Italy, where there is still a strong military presence. The high number of patients observed at the hospital, suffering from genital pathologies and from varicocele in particular, has led to the comparison of the different types of preoperative staging and treatment, both surgical and anesthesiological, of these pathologies. Apart from presenting the epidemiological data of genital diseases, the following work also highlights the importance of careful pre-operative clinical-instrumental staging of varicocele and the satisfying results that can be obtained in treating the same with high ligature of the gonadic vessels under local anesthesia. There are also precise indications as to the use of alternative surgical techniques (microanastomosis, ligature by laparoscopic approach, etc.).

Cancer of the prostate is a statistically important disease in the field of urological neoplastic pathology. The usefulness of mass screening for this tumour is extremely controversial. The most important reports of the congress are given here.

The different criteria to be taken into consideration when carrying out presymptomatic screening of neoplastic diseases are given. Screening is an operation of secondary prevention and can be divided into: 1) mass screening 2) selective (or aimed) screening 3) multifascia screening (check up). The Author gives the fors and againsts of the above types of screening and concludes that they can lead to: 1) only a prolungation of the lead time 2) a more favourable life expectation 3) a normal life expectation with death due to the neoplasm 4) death for natural causes and not for the tumour 5) early death (iatrogenic). The general criteria laid down by the W.H.O. on the suitability of submitting a population to screening are: a) the pathology to be investigated must be an important problem both for health and socially b) a diagnostic protocol must be available for subjects who have a positive test result, as well as an effective treatment protocol for the diagnosed cases c) the investigated pathology must be characterised by a recognisable stage, latent or with early symptoms d) screening methods must be easy to carry out with no risks involved e) the screening must be acceptable for the invited population f) the natural history of the neoplasm must be sufficiently well-known g) the parameters of normality, allowing the positive patients to be distinguished from the negative ones, must be very clear h) assessment of the cost/benefit ratio i) the activity of early diagnosis must be a continuing and not an irregular service, on the basis of established protocols I) the availability of economic, staff and organisational resources must be guaranteed. In any case, the Author proposes that the screening programme be checked in terms of sensitivity (capacity to select the truly ill people), specificity (capacity to select the healthy ones) and predictive value (% value of test reliability).

High incidences for prostatic cancer and mortality related to tumour have a serious impact on society. In these few last years there has been an emerging interest in the opportunity and possibility of a screening programme for this cancer. At present no certain data exist on the utility of a screening programme in asymptomatic males. The only proposable programme appears to be a pilot study to evaluate the capacity to reduce mortality related to prostate cancer or at least to improve the quality of life in cases diagnosed through a screening programme.

From September 1992 to February 1994, 1441 men aged between 50 and 70 years underwent screening with PSA and ER measurement for early diagnosis of prostatic carcinoma. A neoplasm was diagnosed in 1.73% (25/1441) of cases, which being found at an early stage, made it possible to perform prostatectomy and radical radiotherapy on 37.5% and 16.6% of patients respectively. The incidence of the disease was higher than in a previous screening with just ER dosage (1.73% vs 1.1%). Combined PSA and ER also gave higher sensitivity, specificity, overall accuracy and predictiveness compared to the methods taken individually. This combination seems preferable, in view of the greater efficacy and “practicability” compared to protocols which involve the use of USTR, which is less practicable on a large scale due to the length of time required and high costs. The utility of periodic determination of PSA levels in those over fifty years old is emphasised, both for oncological screening controls and to increase the diagnostic accuracy of other clinical tests.

The Author describes the procedures to be followed in the prostatic carcinoma screening project with PSA dosage among professional Italian Army members. This research is included in the Italian prostatic tumour screening project in co-operation with the Department of Urology - University of Padua - Italy.