Castrati singers: surgery for religion and art.

The act of castration was practiced from ancient times. In countries of Middle and Far East, castration was often done to provide eunuchs as guardians of the harems. In Europe and especially in Italy, it was carried out to preserve the male voice unbroken into adult life. From 16th century till the end of 18th century, castrati singers dominated opera with their supernatural voices. Boys were castrated mainly before the age of 9 years and when they grew up they had feminine characteristics, such as smooth, hairless bodies, breasts, infantile penis. The training procedure to become a castrato singer was very intense and lasted up to ten years. The most common surgical technique was either to sever the spermatic cords or crush the testis with the fingers. The voice of a castrato was the outcome of a larynx the size of a child's combined with the lung volume of an adult male. The castrati singers became superstars who dominated opera, singing both male and female roles for more than 200 years. Castrated for art, the beauty, range and flexibility of their voices raised them to mythical status.

Hydronephrosis promotes expression of hypoxia-inducible factor 1 alpha.

BACKGROUND: Obstructive uropathy is argued to involve an ischemia-type tissue injury. Further, hypoxia-inducible factor 1 alpha (HIF-1 alpha) constitutes a nuclear transcription factor normally upregulated under hypoxic conditions. We hypothesized that HIF-1 alpha is expressed in the hydronephrotic renal pelvis, as a result of tissue hypoxia. PATIENTS AND METHODS: Renal pelvis tissue specimens were obtained from 2 patient groups. Group 1 (controls, n = 10) consisted of patients who underwent nephrectomy due to nonobstructive renal malignancy. Group 2 (n = 18) consisted of patients who underwent open procedures due to intractable hydronephrosis, not amenable to conservative measures. HIF-1 alpha detection was conducted via immunohistochemical techniques, while histological alterations in both groups were also recorded. RESULTS: Smooth muscle hypertrophy and urothelial hyperplasia were major findings in group 2. HIF-1 alpha-positive cells (fibroblasts and occasionally macrophages), mainly localized in the stroma, were also found to a greater extent in group 2 (p = 0.0066). CONCLUSION: We conclude that HIF-1 alpha is mainly expressed in stroma fibroblasts of the hydronephrotic renal pelvis, implying the presence of significant tissue hypoxia at the dilated upper urinary tract.

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate.

PURPOSE: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. METHODS: Wistar rats were treated with terazosin (1.2 mg/kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. RESULTS: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the anti-bFGF antibody. In contrast, the same staining in terazosin-treated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. CONCLUSIONS: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis.

Short- and long-term complications of open radical prostatectomy according to the Clavien classification system.

OBJECTIVE: To assess the use of the Clavien classification system in documenting the complications related to open retropubic radical prostatectomy (RRP). PATIENTS AND METHODS: The medical records of 995 patients, who had open RRP during a period of 7 years, were reviewed retrospectively. Short- and long-term complications were classified according to the recently revised Clavien classification system. We also compared the results with a recently reported series of laparoscopic and robotic RRP. RESULTS: The overall complication rate was 26.9%; Grade I, Id, II, IIIa, IIIb and V complications were recorded in 3.4%, 3.9%, 12.8%, 2.6%, 3.8% and 0.3% of cases, respectively. Rectal injuries (10) and postoperative wound infections (24) were included in the Grade I category. Anastomotic leakage was recorded in 39 patients and rated as Grade Id. Grade II included cases of deep vein thrombosis (11), urinary tract infections (42), lymphorrhoeas (22) and haemorrhage requiring transfusion (53). Anastomotic strictures (26) and incisional hernias (38) were included in Grade IIIa and IIIb, respectively. Pulmonary embolism was fatal for three patients (0.3%) of Grade IV and V. CONCLUSIONS: To avoid incoherence in reporting morbidity data, a reproducible and practical classification system is necessary. The Clavien system could provide, after refinement and validation, a common language among urologists.

Differences in presentation characteristics of renal cell carcinoma in the last 25 years: a single center experience.

PURPOSE: The aim of this study was to examine trends in clinicopathological characteristics of renal cell carcinoma (RCC) cases at presentation in a single institution over a 25-years period. PATIENTS AND METHODS: The medical files of 505 patients with histologically confirmed primary RCC from 1981 to 2006 were retrospectively reviewed. Host and tumor characteristics at presentation were compared following stratification by hospitalization period (1981-1990, 1991-2000, and 2001-2006). RESULTS: Age at presentation did not change significantly over time. The incidentally diagnosed cases increased significantly by time (10.2, 40.5, 62.7%), in proportion to small (<4 cm) tumors (8.6, 17.3, 30.6%), while tumor diameter decreased significantly (8.5 +/- 3.8, 7.4 +/- 3.5, 5.8 +/- 2.9). The rate of organ-confined tumors increased significantly (42.1, 63.6, 68.9%), followed by a less pronounced decrease of metastatic cases (12.3, 8.9, 6.8%). CONCLUSIONS: The evolution of tumor characteristics at presentation in a single institution is apparent within the last 25 years. Major changes were noticed within organ-confined and small tumors and call for familiarization of urologists with nephron-sparing techniques and novel ablation technologies.

Spontaneous perforation of the ureter: clinical presentation and endourologic management.

BACKGROUND AND PURPOSE: Spontaneous perforation of the upper ureter is a rare condition that poses diagnostic and therapeutic problems. We report on five cases from three institutions and discuss the literature. PATIENTS AND METHODS: Five patients presented with renal colic and the imaging modalities used to assess them showed extravasation of urine. RESULTS: The cause of spontaneous perforation of the ureter was a ureteral stone in one case and was unknown in four cases. In all cases, a Double-J ureteral stent was inserted under fluoroscopy. Urinoma was percutaneously drained in only one patient. Repeat imaging showed normal renal function and morphology in all patients. CONCLUSION: Spontaneous perforation of the ureter should be suspected after renal colic. Endourologic treatment offers excellent results, even for the management of acute complications.

Vascular endothelial growth factor protein expression in a renal ablation rabbit model under prolonged warm and cold ischemia.

BACKGROUND/AIMS: To establish a potential correlation between renal and systemic production of vascular endothelial growth factor (VEGF) protein after prolonged ischemia in a renal ablation model under normothermic and hypothermic conditions. METHODS: 38 uninephrectomized New Zealand rabbits were divided into 5 groups. The rabbits of each group underwent partial nephrectomy under 90 and 60 min of warm and 90 and 120 min of cold ischemia, except for the sham group (S), which served as control. Serum creatinine (SCr) and blood-urea-nitrogen (BUN) levels were assessed. On the 15th postoperative day (POD), the animals were euthanized and the remaining kidneys were evaluated. VEGF immunohistochemistry and serum Western blot analysis were performed. RESULTS: In comparison to the control group, groups 60W, 90C and 120C showed 1.6-, 1.14- and 1.75-fold decreases, respectively, while the production of VEGF was significantly declined by 7.4-fold in group 90W (p < 0.05). Immunohistochemistry revealed prominent VEGF staining in the above-mentioned three groups, while in group 90W staining was negative. Serum biochemistry and microscopic evaluation verified the same differentiation. CONCLUSION: Renal and serum VEGF seem to have an analogous expression under conditions of prolonged ischemia. VEGF is overexpressed in hypothermic conditions compared to warm ischemia exceeding 60 min. Hypothermia can be more advantageous in a procedure applying prolonged ischemia.

Multiple metastases of prostatic adenocarcinoma to the urethra after radical prostatectomy.

We present a rare case of multiple metastases of a prostatic adenocarcinoma to the urethra. Radical prostatectomy had been performed 13 years before, and during this time he had been frequently treated with transurethral resections of the bladder neck for obstructive urinary symptoms.

Enucleoresection for the elective treatment of small renal cell carcinoma: can it be the treatment of choice?

BACKGROUND: We present our findings in a series of T1 renal cell carcinomas (RCC) treated with excision of the tumor surrounded by a minimal layer of grossly normal parenchyma. PATIENTS AND METHODS: A total of 43 patients who underwent elective nephron-sparing surgery performed with enucleoresection were studied retrospectively. None of the patients had preoperative or intraoperative suspicion of positive nodes and were free from distant metastases before surgery (N0, M0). Patients status was last evaluated in January 2006. RESULTS: Median age was 58.7 years (35-78). Median tumor size was 3.3 cm (1.5-7). There were no major complications such as bleeding and urinary leakage/ urinoma requiring re-operation. Pathological stage was pT1a in 38 (89%), pT1b in 4 (9%) and pT3a in 1 (2%) patient. Median followup was 32 months (6-89). A total of 5 patients with RCC had died as of January 2006. Overall, 3 (6.9%) patients had disease progression, of whom 2 (4.6%) were local recurrence, 1 alone and 1 associated with distant metastases. The overall cancer-specific survival was 95.4%, and the overall progression-free survival was 93%. CONCLUSIONS: Enucleoresection reproduces the results of partial and radical nephrectomy with minimal morbidity. It is a safe and acceptable approach for elective nephronsparing surgery.

Terazosin modifies the content of glycosaminoglycans and the activity of matrix metalloproteinase 2 in the rat ventral prostate.

OBJECTIVES: We have investigated the effects of terazosin on the content of glycosaminoglycans (GAGs), the activity of matrix metalloproteinase 2 (MMP-2) and MMP-9, and the content of tissue inhibitors of MMP (TIMP) in the ventral prostate of Wistar rats. METHODS: Rats were treated with terazosin (0.12, 1.2mg/kg orally every second day) for 120 d. GAGs were isolated and purified from ventral prostate homogenates by lipid extraction, ethanol precipitation, and extensive digestion with pronase and DNAse, separated by electrophoresis, and characterised using specific enzymes. The activity of MMP-2 and MMP-9 was estimated using gelatin zymography and TIMP-1 and TIMP-2 were measured by enzyme-linked immunosorbent assay. RESULTS: Terazosin treatment did not affect the weight of the ventral prostate gland. The prostate contains hyaluronic acid, chondroitin sulfate (CS), dermatan sulfate (DS), and heparan sulfate (HS), MMP-2, TIMP-1, and TIMP-2, but not MMP-9. Terazosin caused a significant increase in the relative content of DS and a significant decrease in the relative content of CS and to a lesser extent of HS. Terazosin evoked a significant increase in the activity of proMMP-2 and MMP-2 but did not affect TIMP. CONCLUSIONS: The differential effect of terazosin treatment in GAG molecules of the rat prostate may be beneficial because CS is known to induce and DS to inhibit cell proliferation. The effect of terazosin on GAGs and MMP-2 may contribute in the molecular mechanisms of terazosin-induced apoptosis because HS and CS have a proapoptotic effect, whereas DS and MMP-2 are antiapoptotic.

Evaluation of the vascular endothelial growth factor (VEGF)-C role in urothelial carcinomas of the bladder.

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) has been associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis and was reported to have an anti-apoptotic and proliferative role. MATERIALS AND METHODS: An immunohistochemical study was applied to 123 specimens of bladder urothelial carcinoma (BUC) to detect VEGF-C and investigate its clinicopathological and prognostic value. VEGF-C-immunostained BUC specimens (123) were statistically correlated with histological grade and stage, patient overall survival and immuno-expression of Ki-67 and bax proteins. RESULTS: VEGF-C immunopositivity (27/123 BUCs, 22.0%) was inversely correlated with tumor stage and bax immunoexpression (p = 0.007 and p = 0.032, respectively). VEGF-C-positive BUCs tended to have better prognosis (univariate analysis). CONCLUSION: VEGF-C might be associated with an anti-apoptotic phenotype. Our controversial results regarding patient survival suggest that the role of VEGF-C in BUC progression and prognosis remains to be clarified.

Efficacy of tolterodine in preventing urge incontinence immediately after prostatectomy.

PURPOSE: Urgency and urge incontinence are frequently observed after prostatectomy. Although symptoms ameliorate within a relatively short time, they usually cause significant stress and anxiety to the patient as far as their duration is concerned. Aim of our study was to determine the efficacy of tolterodine in preventing urgency and urge incontinence after catheter removal in patients that underwent prostatectomy for benign prostate hyperplasia. PATIENTS AND METHODS: Twenty-seven patients with moderate/severe lower urinary tract symptoms due to benign prostatic enlargement, scheduled for prostatectomy, were randomised into two groups, Group A (14 pts) received tolterodine 2 mg b.i.d starting the day of surgery, while group B patients received no such treatment. Tolterodine treatment was discontinued 15 days after catheter removal. All patients completed the International Prostatic Symptom Score (IPSS) and the International Continence Society (ICS-BPH) forms the day before surgery, and three times more, one, fifteen and thirty days after catheter removal. RESULTS: Pre-operative total 1PSS and frequency of urgency/urge incontinence as determined by questions 3 and 4 of the ICS-BPH questionnaire were equally distributed between groups. Tolterodine was well tolerated and no adverse effects were reported. Post-operative IPSS and QoL scores did not differ between groups. However, the frequency of urge incontinence both the first day and fifteen days after catheter removal was significantly lower in the tolterodine group (16.6% vs. 69.2%, p=0.004 and 8.3% vs. 38.4%, p=0.039, respectively). CONCLUSION: Tolterodine was well tolerated in all patients and had a beneficial effect regarding the postoperative urge incontinence. Trials of a larger scale could determine which patients would benefit more, especially according to the presence of storage lower urinary tract symptoms prior to surgery.

MLH1 mismatch repair gene product is associated with apoptotic potential of urothelial bladder carcinomas.

BACKGROUND: Mismatch repair genes are possibly involved in the tumorigenesis and/or progression of bladder cancer, as has been reported in colorectal and other cancers. MATERIALS AND METHODS: The protein expression of one of these genes (MLH1) was examined in 121 patients with urothelial carcinoma (UC) of the bladder by an immunohistochemical technique. RESULTS: Reduced expression of MLH1 protein was detected in 56 cases (46%) and was significantly more frequent in pT2 UCs (p=0.039). In superficial disease (Ta-T1 tumors), preserved expression of the MLH1 protein was detected in tumors with high proliferation indices, as evidenced by Ki-67 immunostaining (p=0.046). Interestingly, low MLH1 levels were positively-associated with the possibly low apoptotic potential of the tumor cells, as evidenced by decreased caspase-3 (CPP32) immunoreactivity (p=0.050). CONCLUSION: A significant proportion of UCs revealed low positivity percentages for MLH1 expression, probably reflecting MLH1 gene dysfunction in the respective cases. Preserved MLH1 expression was associated with highly proliferating cells, which are more likely to need DNA repair systems. A reduced expression of MLH1 may exert an adverse influence on the apoptotic potential of cancer cells.

In vitro biocompatibility between mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG).

BACKGROUND: Mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG) intravesical instillations are widely and effectively used as adjuvant treatment for superficial bladder cancer. In an attempt to improve the efficacy of intravesical therapy, MMC and BCG have also been used in a sequential or an alternating mode. The aim of this study was to assess the in vitro biocompatibility between these agents. MATERIALS AND METHODS: The effect of MMC on BCG clumping tendency was assessed by estimating the number of colony forming units (CFU) of BCG in suspension, during incubation at 37 degrees C for 3 h, with repeated recordings of the suspension optical density (OD). Preparations containing either BCG plus MMC or BCG plus an equivalent amount of sterile water were cultivated using the non-radiometric system BACTEC MGIT 960. The final concentrations of the agents, following transfer of the preparations into the tubes of the system, were 1.25 mg/ml for BCG and 1 mg/ml for MMC. During the cultivation process, the tubes of the system were automatically checked every 60 min for fluorescence emission, which is an indication of mycobacteria growth. A comparative cultivation of the same preparations on Lowenstein-Jensen solid medium was also performed. RESULTS: The OD of the BCG preparation remained almost unaffected for 3 h and was minimally altered by inclusion of MMC. After 34-38 h of cultivation in the BACTEC MGIT 960 system, all 7 cultures of the BCG+sterile water preparations became positive. In contrast, no BCG+MMC specimen became positive after an incubation period of 42 days. Following re-cultivation of the 7 negative BCG+MMC specimens, 6 remained negative, whereas 1 specimen became positive after an incubation period of 22 days. On Löwenstein-Jensen medium, growth of mycobacteria was noted only in the BCG+sterile water specimens and not in the BCG+MMC specimens. CONCLUSION: The results of this study indicate that, although MMC has no apparent effect on BCG tendency to form clumps in suspension, it may inhibit its growth in vitro. However, this does not necessarily compromise BCG anti-tumour activity. As the in vivo interaction of the drugs may be different, the efficacy of the combined BCG+MMC treatment should be defined in clinical trials.

Nuclear hTERT immunohistochemical expression is associated with survival of patients with urothelial bladder cancer.

BACKGROUND: The role of telomere in tumorigenesis is complex. While telomerase activation is suggested to be necessary for tumor growth, it may also help in diminishing genetic instability. The expressions of the telomerase reverse transcriptase/hTERT and the telomerase associated protein-1/hTEP-1 were investigated in relation to clinicopathological parameters and various proliferative and apoptotic biological markers. MATERIALS AND METHODS: The immunohistochemical method ABC/HRP was performed on paraffin sections of 132 patients with urothelial bladder carcinomas to detect the proteins hTERT, hTEP-1, Ki-67, bcl-2, p53 and caspase-3. RESULTS: The hTEP-1 protein was localized in the cytoplasm of cancerous cells (56.6%), while the hTERT protein was detected in the nuclei and the cytoplasm of cancerous cells (57.6% and 45.5%, respectively). hTEP-1 demonstrated an association with lower stage of the disease (p = 0.036), as well as both nuclear and cytoplasmic hTERT (p = 0.018 and p = 0.0001, respectively). Cytoplasmic hTERT showed inverse correlation with the mutant p53 protein (p = 0.047), while both cytoplasmic hTERT and hTEP-1 demonstrated parallel correlation with caspase-3 (p = 0.004 and p = 0.048, respectively). Nuclear hTERT associated with improved overall survival in multivariate analysis (p = 0.007). CONCLUSION: The association of the hTERT protein with low stage urothelial carcinomas and improved patients' survival is in keeping with the idea that the early activation of telomerase may protect against genetic instability and the prevalence of aggressive malignant clones.

The effect of intravesical Bacillus Calmette-Guerin instillations on the expression of inducible nitric oxide synthase in humans.

The activation of the inducible isoform of nitric oxide synthase (NOS) is associated with the production of large quantities of nitric oxide in response to cytokine stimulation. Bacillus Calmette-Guerin (BCG) mode of action against bladder carcinoma remains unclear, although a plethora of local and systemic events may follow its intravesical instillation. The present study was designed to investigate the expression of inducible NOS in normal and neoplastic urothelium and its alteration following tumor resection and subsequent intravesical immunotherapy. Bladder carcinoma and autologous normal bladder tissue specimens were procured from 36 patients undergoing transurethral resection. Tissue specimens were obtained from the same patients at first cystoscopy following six weekly intravesical instillations. Inducible NOS protein expression was assessed by immunohistochemistry in all tissue specimens. Immunostaining of normal urothelium for iNOS before treatment was negative in all but four cases. BCG treatment induced iNOS expression in tumor-free bladder tissue in 24 cases (66.6%). There were only four early tumor recurrences; interestingly, they corresponded to the cases with tumor cells expressing iNOS before BCG treatment, while novel tumors were also iNOS immunoreactive. BCG upregulated iNOS expression in normal human urothelial cells in vivo suggesting a role for nitric oxide in BCG mediated antitumor activity. Inducible NOS was detected in certain tumor specimens before and after BCG treatment implying a possible involvement in pro-tumor action.

DNA ploidy and immunomarking of bladder urothelial tumors before and after intravesical bacillus Calmette-Guérin treatment.

OBJECTIVE: To investigate DNA ploidy and immunoexpression of Ki-67 and p53 as predictivefactors in cases of superficial urothelial cell carcinoma (UCC) treated with bacillus Calmette-Guérin (BCG). STUDY DESIGN: Samples were obtained from 66 patients with UCC (pTa grade 3 or high grade and pT1 independent of grade or with concomitant carcinoma in situ) before and after intravesical BCG treatment. DNA ploidy analysis (ploidy balance, degree of hyperploidy and aneuploidy, proliferation index) was done by static cytometry. Ki-67 and p53 were analyzed immunohistochemically in paraffin-embedded tissue, and their quantification was carried out using an image analysis system. RESULTS: During a mean follow-up of 63.8 months, 31 of the 66 patients developed recurrent tumors (46.9%). DNA ploidy analysis showed that ploidy balance as well as degree of hyperploidy and aneuploidy were not statistically different between recurrent and nonrecurrent tumors. Only proliferation index was statistically significant between recurrent and nonrecurrent tumors. No statistically significant difference was observed in the percentage of Ki-67- and p53-positive cells between primary tumors that recurred and those that did not. CONCLUSION: These findings suggest that only proliferation index has predictive value for recurrence and progression in UCC treated with BCG.

Prognostic significance of metallothionein expression in renal cell carcinoma.

BACKGROUND: Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. PATIENTS AND METHODS: The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival). RESULTS: Positive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25-50% of tumor cells in 7 cases, and in a percentage of 50-75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. CONCLUSIONS: The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter.

Expression of transforming growth factor beta in renal cell carcinoma and matched non-involved renal tissue.

TGFbeta1 is one of several cytokines produced by proximal tubular and renal cancer cells. Previous studies have been mainly focused on determining plasma or serum TGFbeta levels, its effect on RCC cultures, and the expression of TGFbeta mRNA. Cancerous and autologous normal kidney samples were obtained from 24 patients treated by radical nephrectomy. TGFbeta1 expression was determined using a semi quantitative Western blot analysis and immunohistochemistry. Blot densities and immunohistochemical expression intensities in normal and neoplastic tissue were compared, and subsequently correlated to tumor stage, histological type and nuclear grade. All tissue samples examined expressed TGFbeta1; mean tumor to non-involved kidney spot density ratio correlated with advancing stage and higher nuclear grade. The overexpression of TGFbeta1 in certain RCCs may partially explain their resistance to the growth suppression action of TGFbeta. The correlation with tumor stage and grade indicates a possible role in the development of metastatic potential as well as in host's immune response modulation.

Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study.

OBJECTIVES: To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC. METHODS: Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups. RESULTS: The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant). CONCLUSIONS: The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.