Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica.

BACKGROUND: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.

The novel hormone INSL3 is expressed in human testicular Leydig cell tumors: a clinical and immunohistochemical study.

Insulin-like 3 (INSL3) is a novel peptidic hormone member of the relaxin-insulin-like family of peptide factors. It is almost exclusively produced by Leydig cells within the testis and participates to the complex mechanisms leading to physiological testicular descent during embryonic development. We performed a retrospective study evaluating clinical and histopathological characteristics of 13 patients surgically treated for testicular tumor and diagnosed to be affected by Leydig cell tumor (LCT). Furthermore, it was possible to retrieve the archived paraffin embedded tumor together with neighboring healthy testicular tissue of all subjects affected by LCT (12 benign and 1 malignant form), that were analyzed for INSL-3 expression. Immunohistochemical analysis of the tumor sections of the 13 patients affected by LCT demonstrated constitutive expression of INSL3 protein in all LCT, irrespective of the histological pattern of each LCT and with no significant differences of staining intensity between all tumors. In particular, no gross differences were evident between the staining for INSL3 in the 12 benign LCTs and the only one showing malignant clinical behavior. The present study shows that LCTs, a very rare form of testicular tumor with no proven specific serum and histological markers, express a novel member of the relaxin-insulin-like family of peptide factors previously identified as a secretory product of Leydig cells and named INSL3. Thus, there could be the possibility to evaluate the expression and secretion of this novel hormone as a marker of this rare testicular tumor.

Lessons from 52 patients with leydig cell tumor of the testis: the GUONE (North-Eastern Uro-Oncological Group, Italy) experience.

INTRODUCTION: The goal of the study was to define treatment rules for the uncommon, rarely (10%) malignant and chemorefractory Leydig cell tumors (LCT) of the testis. METHODS: The main clinical data of patients treated in centers affiliated to the GUONE (North-Eastern Uro-Oncological Group, Italy) were reviewed. We considered 52 patients (54 tumors, 2 bilateral) whose ages ranged from 13 to 70 years (mean 36). Of the treatments performed, 52 were orchiectomies and 2 were enucleations (unfavorable pathology in only 2 tumors). There were 5 lymphadenectomies (retroperitoneal lymph node dissections): 2 for suspected stage II disease and 1 each for unfavorable pathology, bilateral disease and associated Sertoli tumor (pathology: pN0 in all cases). The length of follow-up ranged from 15 to 249 months (mean 81). RESULTS: There was no relapse in 51 patients and 1 died as a result of metastatic disease (orchiectomy at the age of 70; unremarkable pathology). CONCLUSIONS: Malignant LCT seems to be, in our experience, less frequent than previously reported. Age and pathology are useful prognostic factors, but their predictive value should never be considered absolute. Enucleation seems justified in young patients with favorable pathology. In clinical stage I LCT, retroperitoneal lymph node dissection should be offered to older patients and/or to patients with unfavorable pathology. A prolonged follow-up is mandatory.

IGG practice guidelines on germ cell tumor in adult male patients.

Germ cell tumors are rare neoplasms that affect young males. Nearly 99% of patients with localized stage I disease and nearly 80% of patients with metastatic disease can be cured. Even patients who relapse following chemotherapy can achieve a long-term survival in approximately 30-40% of cases. The main objective in early stages and in good prognosis patients has changed in recent years, and it has become of major importance to reduce treatment-related morbidity without compromising the excellent long-term survival rate. In poor prognosis patients, there is a correlation between the experience of the treating institution and the long-term clinical outcome of the patients, particularly when the most sophisticated therapies are needed. So far, of utmost importance is the information from updated practice guidelines for the diagnosis and treatment of germ cell tumors. The Italian Germ cell cancer Group (IGG) has developed the following clinical recommendations, which identify the current standards in diagnosis and treatment of germ cell tumors in adult males.

Estradiol plasma levels elevation during follow-up for testicular Leydig-cell tumor is not an unfailing sign of recurrence.

We report a case of a benign testicular Leydig-Cell Tumor (LCT) that deceived us because of an estradiol (E2) plasma levels elevation 27 months after radical orchiectomy in a body builder patient with habits of red meat abuse and no steroid assumption, without any sign of tumor recurrence. The patient was therefore asked to stop red meat assumption and E2 plasma levels returned normal. The restoration of red meat assumption showed a trend of increasing E2 plasma levels above normal range. Despite the documented usefulness of E2 plasma levels evaluation during the follow-up of LCT, elevation of this hormone could be related to other causes and presence of the so-called evironmental xenoestrogens may be one of these.

Sexual counseling improved erectile rehabilitation after non-nerve-sparing radical retropubic prostatectomy or cystectomy--results of a randomized prospective study.

AIM: The efficacy of prostaglandin E1 (PGE1)-intracavernous injection (ICI) therapy for erectile dysfunction (ED) after non-nerve-sparing (NNS) radical pelvic surgery depends on patient compliance. The purpose of this study was to verify the utility of sexual counseling in ICI in terms of treatment efficacy, compliance, and dropout rate. METHODS: In this prospective randomized study, 57 patients with ED after NNS radical prostatectomy or cystectomy were divided: 29 patients (group SC+) were treated with sexual counseling and PGE1-ICI therapy; the others 28 (group SC-) were treated with only ICI. At the start of the study all patients were administered the International Index of Erectile Function (IIEF) questionnaire and ICI training test; follow-up (at 3, 6, 9, 12, 18 months) was achieved by home Sildenafil test and ambulatory IIEF test; sexual counseling was provided only to group SC+. RESULTS: The mean IIEF score at the end of study was 26.5 (SC+) vs. 24.3 (SC-) (P < 0.05); eight patients (SC+, 27.5%) became responders to home Sildenafil vs. five (SC-, 17.8%) (P < 0.05); no dropout cases occurred (SC+) vs. eight (SC-, 28.5%) (P < 0.05). Moreover, we recorded best IIEF scores in group SC+ in sexual satisfaction (P < 0.05), sexual desire (P < 0.05), orgasmic function, and general satisfaction. Mean PGE1 doses were better in group SC+ (P < 0.05). ICI-oriented sexual counseling was utilized to motivate couples, to improve sexual intercourses, to correct mistakes in ICI administration. At the end of follow-up 21 patients (SC+) declared themselves satisfied vs. 12 (SC-). CONCLUSIONS: ICI-oriented sexual counseling in ICI increased the efficacy of treatment, the compliance, and Sildenafil responders rate, decreased the dropout rate.

Cellular and molecular gateways to urolithiasis: a new insight.

Urolithiasis is a relevant clinical problem in everyday practice with a subsequent burden for the health system. Urolithiasis is classically explained as the derangement in the process of biomineralization involving the equilibrium between promoters and inhibitors of crystallization: a deficit of one or several inhibitors or an excess of one or several promoters plays a pivotal role in the stone formation. The revolutionary introduction of the molecular biology in medicine has given a new insight in urolithiasis too. Genetic factors have also been postulated to play an important role. A review of the current knowledge on urolithiasis based upon a molecular and genetic approach is reported.

Late recurrence of clinical stage I seminoma of the testis after 12 years despite adjuvant infradiaphragmatic irradiation.

A patient treated with prophylactic infradiaphragmatic radiation therapy for clinical stage I left testicular pure seminoma developed a large mass of the chest wall 12 years after primary treatment. An incisional biopsy confirmed pure seminoma. After chemotherapy, surgical removal of the residual mass and second-line chemoradiation therapy for persistent seminoma, the patient had a vertebral relapse. He died of progression 24 months after the first relapse despite further therapy.

Predictive medicine in non-malignant urological disorders.

The potential of disease prediction in non-malignant disorders should not be undervalued. Such disorders present several characteristics which make them suitable for disease prediction: they can be wide-spread, strongly affect the patients' quality of life, lead to a heavy burden on social health expenses and have a protracted clinical course. Moreover, people who present a high risk for non-malignant disease can be successfully introduced to long-term preventive measures such as lifestyle modifications, dietary changes and improvement in hygienic conditions. There is a growing demand for developing predictive medical strategies in urology. While urological cancers are the main focus of interest, we analyse the potentialities and challenges of predictive medicine in non-malignant urological disorders, with particular attention to benign prostate hyperplasia and urolithiasis.

[BTA tests in the diagnosis and follow-up of superficial bladder cancer]. / BTA tests in the diagnosis and follow-up of superficial bladder cancer.

We reviewed the literature on Bladder Tumor Antigen (BTA Trak and STat) tests to evaluate the usefulness of such tests in the diagnosis and follow-up of bladder cancer and to compare these tests to routine diagnostic tools. We also report our experience on BTA tests in monitoring tumor recurrence of superficial bladder cancer in 194 patients: a correlation between an augmented risk of tumor recurrence and serial measurements of BTA Trak and positive BTA Stat have been identified. According to the available data, BTA tests can be useful in the diagnosis and follow-up of superficial bladder cancer.

[Mitoxantrone chemoprophylaxis for multirecurrent multifocal superficial bladder tumours: results of a phase 2 controlled study]. / Mitoxantrone chemoprophyaxis for multirecurrent multifocal superficial bladder tumours: results of a phase 2 controlled study.

Twenty-three patients with multifocal superficial bladder cancer (stage Ta - T1) unresponsive to at least 3 different intravesical agents, were enrolled in a phase II study in order to evaluate the prophylactic effects of intravesical Mitoxantrone (20 mg) after complete endoscopic resection (TUR) of any papillary tumor. The median follow-up was 6 months; 19 patients (82%) experienced superficial tumor recurrence, 1 patient (4%) progression to muscle invasion and 3 (13%) were disease-free, respectively. Six patients (26%) experienced local side-effects. The progression rate is acceptable; the side effects are at least similar to those available in the literature, but in our experience, Mitoxantrone has no prophylactic effects against superficial bladder cancer unresponsive to previous treatment.

Non-parasitic chyluria: an interesting case of uncertain interpretation.

Chyluria occurs as a result of communication between the lymphatics and the urinary system. It is a common problem in developing countries. Since its original description by Hippocrates, chyluria has been mentioned frequently in the literature and has remained puzzling in many reports. As a rare occurrence, chyluria may present many diagnostic and therapeutic problems. A man with an interesting history of non-parasitic chyluria and an unusual radiological finding is described herein. The etiology and various treatments of chyluria are discussed.

[Caval involvement in advanced-stage non-seminoma testicular tumors: surgical strategy and long-term results]. / II coinvolgimento cavale nei tumori non seminomatosi del testicolo in stadio avanzato: strategie chirurgiche e risultati a lungo termine.

OBJECTIVES: The involvement of vena cava by residual masses after cytoreductive chemotherapy for bulky metastatic germ cell tumors is a rare but possible event. It could ensue by tumor invasion of the inferior vena cava (IVC), venous or neoplastic thrombosis, or by close adherence and encasement of IVC by scar tissue containing fibrosis or cancer; it usually occurs in right testicular neoplasms. In this study we evaluated a group of nine over 86 patients who underwent IVC (and possibly aortic) surgery for post-chemotherapy residual masses and we assessed long term oncological and functional efficacy of the procedure. MATERIALS AND METHODS: Between 1980 and 1997, 86 patients underwent retroperitoneal lymphadenectomy (RPLND) after induction or additional salvage chemotherapy. A subgroup of nine patients, all with primary tumors of the right testis in stage II C to III, showed evidence of caval involvement, four had caval thrombosis, seven exhibited caval invasion; in one case the IVC was displaced and compressed with no clear evidence of infiltration. Surgical management was: three en-bloc and four restricted vena caval resection and two thrombectomy. RESULTS: Of nine patients who underwent IVC surgery, six are alive and have no evidence of disease (follow-up 43-207 months), while three patients deceased for early progression (6-10 months). There were no major surgical complications: only one patient exhibited a significant lymphedema as a result of the primary vascular involvement or of following IVC surgery. CONCLUSIONS: IVC resection is sometimes necessary to complete RPLND of residual masses: it might be crucial to gain oncological clearance, with moderate long term morbidity even for extensive vena cava resections. Among patients eligible for postchemotherapy RPLND, caval involvement selects a higher risk subgroup that should be addressed to medical centers experienced in IVC neoplastic involvement.