Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study.

OBJECTIVES: To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study. METHODS: Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used. By May 1999, the reviewing pathologist had evaluated 303 specimens. One hundred seven patients were untreated before radical prostatectomy was performed, and 114 and 82 patients had been treated for 3 and 6 months, respectively, with complete androgen blockade. RESULTS: Pathologic organ-confined disease was found in 63.1% of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0% after 3 months of NHT and 37.5% after immediate surgery. Among patients with clinical Stage C tumors, pathologic staging found organ-confined disease in 62.5%, 32.1%, and 11.1% of patients after 6 months of NHT, 3 months of NHT, and immediate surgery, respectively. Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease, but the addition of another 3 months of treatment did not significantly improve this result. A lower degree of benefit was observed in patients with clinical Stage C tumors. CONCLUSIONS: This study shows that complete androgen blockade before surgery is beneficial in men with clinical Stage B disease. The effects are more pronounced after 6 months of NHT than after 3 months.

[Stromal tumor of the ileum (GIST) at the same time as a renal carcinoma. Description of a case and review of the literature]. / Tumore stromale dell'ileo (GIST) sincrono a carcinoma renale. Descrizione di un caso e revisione della letteratura.

The gastrointestinal mesenchymal tumors from a heterogenous group that include several entities: leiomyomas, schwanomas and less differentiated tumors often referred as GIST. These neoplasm are uncommon and their clinical behaviour is most difficult to predict. We describe a malignant gastrointestinal stromal tumor of the ileum coexisting with renal cell carcinoma. The neoplasms were fixed in formaldehyde, embedded in paraffin and stained with hematoxylin-eosin. For immunohistochemical studies deparaffinized tissue sections were incubated with antibodies against vimentin, desmin, muscle specific actin, S100, CD34, GFAP, NSE and keratin. The epithelioid and spindle cells of ileal neoplasm were arranged in interlacing fascicle with occasional palisading and were positive for vimentin and CD34. Positivity for muscle specific actin was focally found. The renal neoplasm required differential diagnosis from metastatic GIST. The morphological and immunohistochemical investigations in our case were consistent with GIST coexisting with primitive renal cell carcinoma. One of the problems connected to the anatomo-clinical evaluation of GIST consist in the difficulty of making a prognosis. An almost complete review of the literature and view point on the topic has been performed. As a conclusion judging from papers regarding this argument, no clear parameters of biological behaviour exist excluding mitotic index.

Comparison of LH-RH analogue 1-month depot and 3-month depot by their hormone levels and pharmacokinetic profile in patients with advanced prostate cancer.

In an open, randomized phase II pharmacokinetic study conducted in Germany and Italy, a total of 42 patients with advanced or metastatic prostate cancer (PCa) were treated for 9 months with the luteinizing hormone-releasing hormone analogue (LH-RH-a) leuprorelin acetate depot in two different formulations. Fifteen patients received the 1-month depot and 27 patients received the newly developed 3-month depot, containing 3.75 mg and 11.25 mg, respectively. In both groups, subcutaneous injections of leuprorelin acetate injected monthly or at 3-month intervals produced a complete down-regulation of the pituitary and led to persistent suppression of testosterone and dihydrotestosterone to the castrate range (< or = 50 ng/dl for testosterone) within the first month of treatment, which thereafter could be maintained over the entire observation period of 9 months. In 10 patients, pretreatment with an antiandrogen for the prevention of clinical flare-up resulted in a slightly more profound and earlier drop in serum testosterone. The 3-month depot showed a higher median peak serum concentration (Cmax) of leuprorelin at 20.8 ng/ml than the 1-month depot at 10.7 ng/ml but, conversely, this did not influence the rise in serum testosterone levels. Cmax occurred at 3 h for the 3-month and at 1 h for the 1-month depot formulation. During the steady state, constant release could be detected, starting on day 3 and day 7 for the 1-month and 3-month depot, respectively. A marked decrease in median prostate-specific antigen levels of 97.8% (1-month depot) and 96.6% (3-month depot) compared with baseline was observed, indicating an objective clinical response for more than 80% of all patients in both arms. Based on European Organization for Research and Treatment of Cancer criteria, the best response in terms of complete/partial remissions and stabilization was comparable in the two arms at 86.7% (1-month depot) and 85.2% (3-month depot). 6.7% in the 1-month group and 3% in the 3-month depot group showed progression of the disease. The most common side effects in both treatment groups were related to hormone deprivation. Both formulations of the potent LH-RH-a leuprorelin acetate were highly effective in the treatment of advanced PCa and led to comparable endocrine and clinical effects.

[Endopyelotomy: mid- and long-term follow up]. / Endopielotomia: follow-up a medio e lungo termine.

We report our experience on 24 UPJ obstruction, that underwent endopyelotomy. The follow-up on these patients range from 12 to 72 months. The success rate, based on patient symptomatology as well as urographical and scintigraphical parameters, was 83.3%. An adequate selection of cases, with grade of hydronephrosis and crossing vessels pre-operatorial detection, would possibly show a further improvement of success rate. The antegrade transpelvic endopyelotomy adopted in the most recent cases, allows the identification of crossing vessels and the performance of a safer endopyelotomy. The average operating time was very short, while morbidity was limited to 3 cases (2 of gross haematuria and 1 urosepsis). All this shows that endopyelotomy is the first choice treatment of UPJ obstruction.

[Post-voiding contraction: evidence and characterization in other 250 urodynamic studies]. / Post-voiding contraction (PVC): evidenza e caratterizzazione in oltre 250 indagini urodinamiche.

We report our experience on PVC detection in 250 consecutive urodynamic evaluations in female patients. We emphasize the absence of evident correlations between the post-voiding contractions (PVCs) and their amplitude and the urodynamic features. We suggest a possible relation between the PVCs and two clinical features: enuresis (80% of cases associated with PVC) and mixed urinary incontinence (61.5%). Defining PVC as an improper form of detrusor instability, probably generated by a reduction of pelvic muscle tone, we underline the role performed by an urodynamic investigation defining urethral sphincter as well pelvic floor activity, this procedure being justified by the notorious interdependence between perineal and detrusorial activity.

Uptake and intracellular distribution of idarubicin in secondary cultures of normal and neoplastic urothelium.

This study analyzes the uptake and endocellular distribution of idarubicin (IDA) in normal and neoplastic urothelial secondary cultures in relation to the changes in concentration and time of exposure. The urothelial lines were isolated by Freshney's method from biopsy fragments taken from five patients with superficial bladder cancer. Pharmacological experiments were carried out on subcultures previously immunophenotypically characterized and did not exceed ten passages. The uptake and endocellular distribution of IDA was analyzed by densitometric image analysis on cells treated for 10, 20, 30 and 60 min and 2 h with scalar dosages from 10 ng/ml to 2430 ng/ml. Microscopic observations and densitometric analyzes revealed that in the cells treated with IDA, fluorescence was higher in the cytoplasm compared to the nucleus and increased with the change in dosage. Moreover, densitometric data showed that IDA uptake in the first 20 min was higher in the neoplastic cells, but after that period its behavior became heterogeneous at 30 and 60 min, while at 2 h there was an inversion of the trend. These results suggest that the in vitro cytotoxicity should be evaluated in order to verify whether the elevated uptake of IDA in the first 20 min of treatment is really correlated to a more elevated toxicity in the neoplastic cells with respect to the normal cells. This is presently under investigation.

Carcinosarcoma of penis. Case report and review of the literature.

AIMS OF THE STUDY: Carcinosarcomas (sarcomatoid carcinomas) are controversial, biphasic tumors composed of both carcinomatous and sarcomatous elements. They are uncommon and occur in numerous locations. At the time of this report only 3 cases of carcinosarcoma of penis have been reported in the literature. The aim of this article is to provide a discussion of these lesions, using informations gleaned from the pertinent literature as well as the personal experience of the authors. METHODS: The formalin-fixed paraffin-embedded tissue was stained with hematoxylin and eosin, reticulum, alcian blue and Mallory's trichrome stains. Section from selected paraffin-embedded blocks, were stained with antibodies to citokeratins, EMA, vimentin, desmin, and a actin. RESULTS: In our case the carcinomatous elements were admixed with areas of "divergent differentiation": spindle-cell and giant-cell sarcomatoid component with bone and cartilage differentiation were noted. In situ carcinoma was also detected. Immunohistochemistry showed reactivity for keratin and epithelial membrane antigen (EMA). In most of pleomorphic spindle elements. Immunoreactivity for vimentin, desmin and actin were focally found. CONCLUSIONS: The carcinosarcomas may demonstrate "divergent" differentiation into bone, cartilage or myogenous tissue, so it is possible that the cell of origin could be heterogeneous. In our case myogenous differentiation was focally found. Although the clinical data, available from the only three cases of the literature, demonstrate that the behaviour of this tumors was not different from those of squamous cell carcinoma, the authors recommended a constant careful follow-up of the patients.

Carboplatin monochemotherapy in elderly patients with nonoperable transitional cell carcinoma of the bladder: a two-stage, phase II study.

Elderly patients with nonoperable transitional cell carcinoma of the bladder need a rather active, but less toxic treatment than full-dose polychemotherapy. This study was designed to determine whether the cisplatin-analogue carboplatin (which is less nephrotoxic and less neurotoxic than the parent compound) has sufficient activity against T2-T4 neoplasms (both nonmetastatic and metastatic) to warrant further development in phase III trials. Carboplatin dose was adjusted according to creatinine clearance, with a maximum dose of 300 mg/m2. The patient selection for this screening for activity was adjusted by the use of the 'optimal' two-stage design. Seventeen patients were enrolled, with a median age of 78 years (range: 70-85), a median performance status of 80% (range: 70-90%); 13 patients were lymph node-negative (10 T2, 2 T3, 1 T4) and 4 had locoregional or distant node metastases. Nine patients had a complete response (3 in the first, 9-patient, stage, and 6 in the second, 8-patient, stage), demonstrating that carboplatin had sufficient activity (at the 'desirable' target level of 35%); almost all responses were observed in T2 patients. Six patients had stable disease, and 2 had disease progression during treatment. The toxicity was acceptable, with only 41% of patients having grade II-III hematologic toxicity. More than 30% of patients were estimated to be free from progressive disease (54% alive) at 24 months. In our opinion carboplatin is suitable to be tested-in a phase III testing versus full-dose radiation therapy-as adjuvant after initial transurethral resection of the prostate in elderly patients with T2 transitional cell carcinoma of the bladder considered radically nonoperable for medical problems.