Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease.

Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07-1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06-1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials.

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease.

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.

Prognostic value of the involvement of the urinary collecting system in renal cell carcinoma.

OBJECTIVES: The prognostic role of the invasion of the urinary collecting system (UCS) by renal cell carcinoma (RCC) has not attracted a notable amount of attention. The aim of this study was to investigate incidence and prognostic value of UCS involvement in RCC. MATERIAL AND METHODS: All pathological reports of radical nephrectomies performed in two centres of urology from November 1983 to December 1999 were reviewed in order to evaluate the invasion of the UCS (calices, renal pelvis, ureter). Patients were divided into two groups according to presence (Group 1) or absence (Group 2) of UCS invasion. The stage was determined according to the TNM 6th edition. Overall and cause-specific survival rates were evaluated. Univariate and multivariate analyses were performed. RESULTS: The evaluable specimens were 671 from the 735 examined; in 64 cases it was not possible to ascertain or to exclude UCS involvement. Invasion of the UCS was found in 59 cases (8.8%). Median follow-up was 59.0 months (range 0-216). Tumours invading the UCS were usually symptomatic, with high nuclear grade and predominantly high stage. At univariate analysis the 5 year overall and cause-specific survival rates of tumours invading the UCS were significantly lower when compared to those without UCS invasion (42.8% versus 60.8% and 45.5% versus 64.7%, respectively). When groups were stratified, according to the pT category, the 5-year cause-specific survival rate was only significantly different for the pT2 category (33.3% versus 76.9%). At the multivariate analysis TNM staging, symptoms at diagnosis and tumour grade were the only independent prognostic factors. CONCLUSION: The invasion of the UCS by RCC is unusual, particularly in small tumours. UCS involvement does not represent an independent prognostic factor. However, in organ-confined tumours (i.e. pT2) UCS involvement has an influence on the prognosis and should be taken into account when planning adjuvant treatments and follow-up.

Is laparoscopic bladder diverticulectomy after transurethral resection of the prostate safe and effective? Comparison with open surgery.

PURPOSE: In a retrospective nonrandomized study, we compared our experience with transurethral resection of the prostate (TURP) plus sequential laparoscopic bladder diverticulectomy with a series of combined open bladder diverticulectomies with transvesical prostatectomy. PATIENTS AND METHODS: We considered 12 consecutive patients (group A) having 16 diverticula who underwent sequential TURP and transperitoneal laparoscopic bladder diverticulectomy and 13 consecutive patients (group B) having 13 diverticula who underwent open bladder diverticulectomy and transvesical prostatectomy. We evaluated the size and position of the diverticulum, adenoma volume, operative time, postoperative hemoglobin variations, analgesia requirement, complications, postoperative hospital stay, and uroflowmetry results. RESULTS: No statistically significant differences existed between the groups in adenoma volume or diverticulum size or position. However, a significantly longer operative time was recorded in group A. The endolaparoscopic approach proved to be statistically superior to open surgery regarding blood loss, postoperative analgesia requirement, and hospital stay. No intraoperative complications were recorded. In addition, no statistically significant difference was found in uroflowmetry results. CONCLUSIONS: In our experience, the endolaparoscopic approach has proved to be safe, effective, and minimally invasive and therefore superior to transvesical prostatectomy and open bladder diverticulectomy. Its only disadvantage is the longer operative time.

The number of lymph nodes examined and staging accuracy in renal cell carcinoma.

OBJECTIVE: To determine the number of lymph nodes that need to be examined to accurately stage the pN variable in patients undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC). PATIENTS AND METHODS: We reviewed the operative and pathology reports of 725 patients with RCC submitted for RN. All tumours were classified using the fifth edition of the Tumour-Nodes-Metastasis classification. For each patient the number of lymph nodes removed was recorded. The patients were divided into five different groups according to the number of nodes removed, i.e. group 1, 1-4; group 2, 5-8; group 3, 9-12; group 4, 13-16; and group 5, >or= 17. We evaluated the factors that affected the number of lymph nodes removed with nodal dissection and the variables that influenced the incidence of nodal involvement. RESULTS: Lymphadenectomy was performed in 608 patients (83.8%); in these patients the rate of lymph node metastases was 13.6%. The median (range) number of nodes removed was 9 (1-43); there was a statistically significant correlation between the number of nodes removed and the percentage of nodal involvement (r = 0.6; P < 0.01). The rate of pN+ was significantly higher in the patients with >or= 13 than in those with < 13 nodes examined (20.8% vs 10.2%; P < 0.001). For organ-confined and locally advanced tumours there was a statistically significant difference in the pN+ rate between patients with < 13 or >or= 13 nodes examined (3.4% vs 10.5%, and 19.7% vs. 32.2%, respectively). CONCLUSIONS: The proportion of tumours classified as pN+ increased with the number of lymph nodes examined. In RCC,> 12 lymph nodes need to be assessed for optimal staging.

Sequential transurethral resection of the prostate and laparoscopic bladder diverticulectomy: comparison with open surgery.

OBJECTIVES: To compare our experience with transurethral resection of the prostate and sequential laparoscopic bladder diverticulectomy with a previous series of combined open bladder diverticulectomy and transvesical prostatectomy. METHODS: We compared the data of 10 consecutive patients (group 1) who underwent sequential transurethral resection of the prostate and transperitoneal laparoscopic bladder diverticulectomy and 13 consecutive patients (group 2) who underwent traditional combined open bladder diverticulectomy and transvesical prostatectomy. The following parameters were considered: size and position of the diverticulum, transrectal ultrasound adenoma volume, operative time, postoperative hemoglobin variations, analgesic requirement, complications, postoperative hospital stay, and urinary flowmetry. RESULTS: No statistically significant differences existed between the two groups either for diverticulum size (6.8 versus 7.2 cm) or diverticula position. A significant difference was observed in the operative time (247 minutes for group 1 versus 136 minutes for group 2, P <0.0001), mean postoperative hemoglobin decrease (2.6 g/dL for group 1 and 3.9 g/dL for group 2, P = 0.001), analgesic requirement (1.3 ampoules of buprenorphine cloritrate for group 1 versus 1.8 ampoules for group 2, P = 0.45), and postoperative hospital stay (3 days for group 1 versus 9.6 days for group 2, P <0.0001). No statistically significant difference was recorded for control flowmetry. No intraoperative complications were recorded for the two groups. CONCLUSIONS: In our series, sequential transurethral resection of the prostate and transperitoneal laparoscopic diverticulectomy for large diverticula proved to be a safe, effective, and minimally invasive procedure, despite the longer operative times compared with transvesical prostatectomy and open bladder diverticulectomy.

Metabolic effects of single-dose pamidronate administration in prostate cancer patients with bone metastases.

BACKGROUND: Increased osteolysis usually accompanies sclerotic bone metastases from prostate cancer. This provides a rationale for the use of bisphosphonates to treat bone pain and prevent skeletal complications. METHODS: The fasting urinary levels of calcium, hydroxyproline (OHPRO), pyridinolines (PYD), deoxypyridinolines (DPYD), collagen cross-linked N-telopeptide (NTX) and the serum values of calcium, total alkaline phosphatase and relevant bone isoenzyme, bone gla protein (BGP), carboxy-telopeptide of type I collagen (ICTP) and parathyroid hormone (PTH) were determined at baseline and on the 15th, 30th, 60th and 90th days after single-dose (90 mg) pamidronate administration in 35 consecutive prostate cancer patients with bone metastases. These biochemical indices and serum interleukin 6 (IL-6) were also measured after four days in the last consecutive 17 cases. RESULTS: PYD, DPYD and NTX showed a significant decrease lasting four weeks (p<0.01, <0.01 and <0.001, respectively). OHPRO and ICTP did not change significantly. The NTX decline was greater than that of PYD and DPYD (maximum percent decrease: -71.3, -23.1 and -28.2, respectively). Bone formation markers and serum calcium did not change significantly. Serum PTH showed a rapid initial increase followed by a slow decrease (p<0.001). DPYD and NTX patterns did not correlate with changes in bone pain. As observed in the last 17 cases, the maximum osteolysis inhibition after pamidronate occurred on the fourth day after drug infusion. Serum IL-6 levels showed a short-lived decrease preceded by a transient rise on the fourth day. CONCLUSIONS: Pamidronate is able to induce a decrease in bone resorption without significantly influencing bone formation. The maximum decrease in bone resorption occurs very early. NTX is the most sensitive bone resorption marker in bisphosphonate therapy monitoring. Changes in IL-6 but not bone resorption markers may be useful in the prediction of symptomatic response.

Metabolic bone disease induced by prostate cancer: rationale for the use of bisphosphonates.

PURPOSE: Increasing evidences indicate that despite the osteoblastic nature of metastatic bone lesions due to prostate cancer osteolysis is a regular feature and may cause skeletal morbidity. This observation provides the rationale for the use of bisphosphonates for managing bone metastatic prostate cancer. MATERIALS AND METHODS: We reviewed the literature on the mechanisms by which prostate cancer affects bone cell function and disrupts physiological bone turnover. We also summarized the clinical results of bisphosphonate for treating bone pain in patients with prostate cancer. RESULTS: Metastatic prostate cancer in bone interferes with physiological bone remodeling by abnormal release of the hormones and paracrine factors physiologically involved in the modulation of osteoblastic and osteoclastic activity. Tumor induced bone formation and resorption develop within the same metastasis but excessive new bone is deposited away from bone resorption sites and does not contribute to bone strength. The increase in bone resorption may also be a generalized phenomenon that is most likely due to iatrogenic osteoporosis or related to hyperparathyroidism in response to the increased calcium demand. The bone resorption index in patients with bone metastatic prostate cancer correlates with bone pain and is an independent predictor of adverse skeletal events. However, small clinical studies of the efficacy of bisphosphonates for controlling bone pain in patients with prostate cancer show contradictory results. CONCLUSIONS: Improved understanding of the pathophysiology of prostate cancer induced metabolic bone disease implies that bisphosphonates may have a role in the treatment of this disorder. This issue is being addressed by large-scale ongoing randomized studies.

Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen, and insulin-like growth factor-1 in advanced prostate cancer patients.

BACKGROUND: The concept that neuroendocrine cells detected within prostate adenocarcinoma produce paracrine factors, that may exert a proliferative effect on exocrine prostate tumor cells, provides a rationale for the use of somatostatin analogs with the aim to counteract or delay the tumor progression. This study was designed to provide preliminary information on the effect of the administration of a long-acting somatostatin analog, lanreotide, on plasma levels of chromogranin A (CgA). Secondary aims were the evaluation of changes in circulating prostate-specific antigen (PSA) and insulin-like growth factor-1 (IGF-1). METHODS: Lanreotide (Ipstyl 30 mg; Ipsen, Milan, Italy) was administered intramuscularly every 14 days for 2 months to nine heavily pretreated prostate cancer patients with hormone refractory disease. All patients had, at baseline conditions, CgA values above the normal range. Androgen deprivation was maintained during the study period, while other concomitant antineoplastic treatments were not allowed. Serum PSA levels and plasma CgA and IGF-1 values were measured every week. RESULTS: Lanreotide treatment was very well tolerated and no patient experienced major toxicity. Plasma CgA values at baseline: mean 109 U/liter, standard deviation +/- 85 decreased significantly after treatment as follows: 42 U/liter, +/- 17.8; 27.2 U/liter +/- 13.6; 31.4 U/liter, +/- 17.8 and 27.6 U/liter, +/- 17.0; after 7, 14, 21, and 28 days, respectively (P < 0.01, Friedman ANOVA). Serum PSA did not change. Baseline IGF-1 was found to be above the detection limit in four cases, all of them showing a decrease after lanreotide. CONCLUSIONS: Lanreotide administration to prostate cancer patients induces a decrease in plasma CgA and IGF-1 levels, without any influence on serum PSA values. Prostate 47:205-211, 2001.

Potential clinical value of circulating chromogranin A in patients with prostate carcinoma.

BACKGROUND: Neuroendocrine (NE) differentiation of prostate adenocarcinoma has received increasing attention in recent years as a result of possible implications for prognosis and therapy. The presence of NE tumor subpopulation can be gauged non invasively by measuring circulating levels of secretory products, primarily chromogranin A (CgA). METHODS: This article provides a review on published papers evaluating circulating CgA in prostate cancer patients. RESULTS: Circulating CgA levels were found to be higher in prostate cancer patients than in patients with benign or pre-malignant prostatic diseases. In patients with malignancy, they correlated either to the stage of disease or to the condition of hormone refractoriness. CgA levels did not correlate with serum prostate specific antigen (PSA) and were supranormal in the majority of advanced patients with PSA within normality. In hormone refractory cases, elevated CgA was a significant predictor of poor prognosis, independently from serum PSA. CgA values were not substantially affected by either endocrine therapy or chemotherapy. They were found to increase during androgen deprivation in some cases and this trend preceded that of PSA. The administration of a somatostatin analog in hormone refractory cases was able to reduce plasma CgA values consistently. CONCLUSIONS: Present data suggest a potential role of circulating CgA in the management of prostate cancer patients. CgA determination may be useful diagnostically and prognostically and could offer complementary information with respect to PSA. Serial evaluation of circulating CgA could provide information on changes in the NE phenotype expression as a consequence of tumor progression and/or treatment administration.

Relationship between neuroendocrine features and prognostic parameters in human prostate adenocarcinoma.

PURPOSE: The biological behaviour of prostate cancer is highly variable and prediction by the commonly employed prognostic parameters is not sufficient. The concept of neuroendocrine (NE) differentiation in prostate adenocarcinoma has recently received increasing attention due to possible implications for prognosis and therapy. MATERIALS AND METHODS: Core needle biopsies from 142 newly diagnosed patients were immunohistochemically examined for the coexistence of NE differentiation using an antibody against chromogranin A (CgA). Circulating CgA was available in 106 of these patients. RESULTS: NE differentiation was found in 64 (45.1%) tumors. Among them 29 (20.4%) had CgA positive cells scattered or focally distributed in less than 5% per mm3 of tumor tissues, 26 (18.3%) between 5% and 10% and 9 (6.4%) more than 10%, respectively. There was a significant correlation between the extent of NE features and either Gleason score (P < 0.01) or stage of disease. Circulating CgA but not PSA correlated with immunohistochemical CgA (P < 0.03) particularly in metastatic cases. CONCLUSIONS: These data support the concept that NE differentiation in human prostate cancer has a negative prognostic significance. Circulating CgA levels reflect immunohistochemical findings.

Circulating neuroendocrine markers in patients with prostate carcinoma.

BACKGROUND: Circulating neuroendocrine markers were measured in patients with prostate carcinoma (PC), prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) with the goal to: 1) evaluate the differences in the expression of these markers in patients with benign, premalignant, and primary or metastatic PC; 2) evaluate their prognostic significance; 3) compare values in patients with hormone-naive and hormone-refractory disease; and 4) assess changes after androgen deprivation or chemotherapy. METHODS: Serum neuron specific enolase (NSE) (immunoradiometric assay) and plasma chromogranin A (CgA) (enzyme-linked immunoadsorbent assay) were evaluated in 141 patients with BPH, 54 patients with PIN, and 159 patients with PC; 119 patients were bearing hormone-naive disease and 40 were bearing hormone-refractory disease. CgA was monitored in 31 patients submitted to androgen deprivation and in 24 patients receiving chemotherapy. RESULTS: Supranormal CgA was observed more frequently in patients with American Urologic Association (AUA) Stage D2 disease (45.5%) compared with those with Stage D1 disease (33.3%), Stage C disease (16.7%), Stage A/B disease (18.8%), PIN (25.9%), and BPH (17.0%) (P < 0.02). Supranormal NSE did not change in any of the patient subgroups. Elevated CgA was observed in 36.0% of patients with metastases who had hormone-naive disease and in 45.0% of patients with hormone-refractory disease (P value not significant). Supranormal NSE and CgA values were predictors for poor prognosis in patients with hormone-refractory disease. Elevated baseline CgA values decreased > 50% in 1 of 12 patients who received luteinizing hormone-releasing hormone analogs and in 2 of 12 patients who underwent chemotherapy. CONCLUSIONS: CgA appears to reflect the neuroendocrine activity of PC better than NSE. Elevated CgA values correlate with poor prognosis and are scarcely influenced by either endocrine therapy or chemotherapy.

[Pelvic ultrasound monitoring of lymphocele in patients treated with radical prostatectomy]. / Monitoraggio con ecografia pelvica dei linfoceli nei pazienti sottoposti a prostatectomia radicale.

Pelvic lymphoceles, occurred in patients undergone radical retropubic prostatectomy, are believed to increase the risk of deep venous thrombosis and so thromboembolic complications. The authors' aim is to evaluate the usefulness of pelvic ultrasonography in the diagnosis and in the possible early treatment of pelvic lymphoceles. Fifty-eight patients undergone radical prostatectomy and pelvic lymphadenectomy, between January '98 and December '99, underwent a pelvic ultrasonography in VII post-operative day. When a symptomatic or large (over 5 cm) lymphocele was found, it was treated with ultrasound (US) guided drainage. In the study, the following parameters were considered: lymphocele occurrence, size, location and treatment and thromboembolic complication. Statistical analysis was carried out with Fisher's exact test. Pelvic US showed a lymphocele in 23 out of 58 (40%) patients. Mean size was 5 cm. Deep venous thrombosis occurred in 4 patients, all with pelvic lymphoceles. No thromboembolic complications were recorded. In our experience, pelvic ultrasound has shown to be an easy e reliable tool for diagnosis and percutaneous treatment of pelvic lymphoceles.

Changes in free and free-to-total prostate specific antigen after androgen deprivation or chemotherapy in patients with advanced prostate cancer.

PURPOSE: To provide preliminary data on whether the diagnostic role of serum prostate specific antigen (PSA) in assessing the response to treatment is improved by concomitant free PSA evaluation both markers were evaluated in 42 patients with advanced prostate cancer who received hormonal therapy and 57 with hormone refractory disease who received chemotherapy. MATERIALS AND METHODS: PSA was assessed at baseline and every 3 months during treatment. Free PSA was assessed in stored serum samples obtained at baseline and at maximum PSA decrease. Free PSA was not measurable in 17 patients who received androgen deprivation (40.5%) and 2 who received chemotherapy (3.5%) because it was less than 1.5 ng./ml. RESULTS: Of the 21 patients with greater than 50% PSA decrease after hormonal therapy free-to-total PSA increased in 12 (57.2%) and decreased in 9 (42.9%). Of the 20 patients with PSA response after chemotherapy free-to-total PSA increased in 18 (90.0%) and decreased in 2 (10.0%). Free-to-total PSA increased in 12 of the 20 patients (60.0%) with PSA stabilization after chemotherapy. Patients with an increase in free-to-total PSA after chemotherapy had greater survival compared to those with a decrease or no change (19.8 versus 15.5 months, respectively, p <0.03). CONCLUSIONS: These data suggest that an effective cytotoxic regimen mainly affects the protein bound PSA fraction. The absence of a clear predominant pattern of free-to-total PSA in patients with PSA response to hormonal therapy and the high percentage of hormone sensitive patients in whom free PSA was not assessable at maximum PSA decrease suggest that free PSA evaluation is less useful in prostate cancer patients undergoing androgen deprivation.

Randomized comparison of goserelin acetate versus mitomycin C plus goserelin acetate in previously untreated prostate cancer patients with bone metastases.

In a prospective trial conducted by the Gruppo Onco Urologico Piemontese, newly diagnosed prostate cancer patients with bone metastases were randomized to receive goserelin (3.6 mg subcutaneously every 4 weeks) or goserelin plus mitomycin at 14 mg/m2 i.v. every 6 weeks. Treatment was planned to be continued until progression. The study was interrupted because of inadequate accrual rate when 63 patients had been recruited. A long-term follow-up (median, 47 months), performed to counterbalance the limited number of patients included, revealed no difference in time to progression and overall survival between the study treatments. However, 56.5% of assessable patients allocated to the chemotherapy arm presented a > or =90% reduction of prostate-specific antigen levels compared with 36.3% in the goserelin group, and previously elevated levels normalized in 73.9% versus 45.4%. Non-progressing patients received 5-7 cycles of mitomycin C with acceptable toxicity, but the cytotoxic treatment was interrupted early in all cases within the first year due to cumulative myelotoxicity. In conclusion, the results, although inconclusive, fail to support a clear advantage in terms of cost/benefit of chemotherapy plus hormone therapy over hormone treatment alone in advanced prostate cancer with bone involvement.

Osteoblastic flare assessed by serum alkaline phosphatase activity is an index of short duration of response in prostate cancer patients with bone metastases submitted to systemic therapy.Gruppo Onco Urologico Piemontese (G.O.U.P).

A transient rise in serum alkaline phosphatase (ALP) activity (ALP flare) after androgen deprivation in prostate cancer patients with bone metastases has been previously correlated with both response to therapy and poor prognosis. In the present study we analyzed data coming from an Italian multicenter phase III, trial aimed to compare the efficacy of treatment with goserelin alone with that of goserelin plus mitomycin C. Sixty-seven bone metastatic patients were enrolled: 32 were treated with goserelin and 35 with and goserelin plus mitomycin. 58 cases had ALP measured every month; and were considered for flare assessment. Remarkably elevated ALP and PSA levels at baseline were significantly correlated with poor prognosis. The addition of mitomycin to goserelin resulted in a greater percent reduction of PSA values with respect to goserelin alone but did not augment the time to progression and overall survival. The monthly profile of ALP serum levels was superimposable in patients assigned to hormone therapy or chemotherapy plus hormone therapy. Patients showing a flare in ALP activity (transient rise > 15% in ALP values with respect to baseline at the first month) were classified as responders to therapy or as having stable disease upon PSA evaluation and/or at bone pain assessment, but had a shorter time to progression (median 12 months) in comparison to those showing a different ALP pattern (median 23 months). The measurement of flare in ALP activity during androgen suppression with or without concomitant mitomycin administration, may permit the early identification of patients who are likely to progress rapidly, and hence be candidate for more aggressive treatments.

[Treatment of voluminous renal cysts with drainage and repeated percutaneous administration of alcohol. Our experience]. / Trattamento di cisti renali voluminose mediante svuotamento ed alcoolizzazione percutanea ripetuta. Nostra esperienza.

The Authors report their experience on the treatment of simple voluminous renal cysts with an echo-guided puncture followed by a sclerosis, that is repeated thrice, with an endocavitary injection of pure alcohol. Since the fair results (94% of success) that were obtained after a mean follow-up of 16 months, the low invasivity of the method and the benignity of the disease, should propose the method itself as the first approach for the treatment of voluminous but not complicated renal cysts.

[Transvaginal ultrasonography in the diagnosis of urethral diverticula]. / L'échographie endovaginale dans le diagnostic des diverticules urétraux.

The authors report their experience on transvaginal ultrasound in the diagnosis of urethral diverticula, using a high frequency linear probe, that is generally employed for transrectal prostate sonography. This non invasive method seems to be more reliable than voiding cystourethrography. This investigation may be recommended in women who have symptoms of lower urinary tract infection, urethral pain, dyspareunia, palpable mass of the anterior vaginal wall.

Monoclonal antibody Ki-67 in the study of the proliferative activity of bladder carcinoma.

We studied the proliferative activity of bladder carcinoma using monoclonal antibody Ki-67, which is able to stain a nuclear antigen exclusively present in cells in the cell cycle, that is with activated deoxyribonucleic acid (DNA). We used this immunohistochemical technique on neoplastic tissue removed by transurethral resection from 101 patients. A significant correlation was observed (p less than 0.003) between cells with activated DNA and histological grading, even though within the context of each grade we observed tumors with a different proliferation index. Furthermore, we studied the location of the activated cells in the context of the tumor. In invasive tumors (stages T1 to T4) cells with activated DNA were always present at the base of implant of the tumor and in the neoplastic tissue that infiltrates the bladder wall. In regard to noninvasive tumors (stage Ta), in 57% of the cases most cells with activated DNA were present in the vegetative portion of the tumor and there were no recurrences at followup, while in 43% of the cases such cells were present also or especially at the base of implant of the tumor, near the lamina propria. In the latter patients we observed a 94% recurrence rate. These results suggest that the immunohistochemical assessment of the proliferative activity of transitional tumors of the bladder, using monoclonal antibody Ki-67, and the evaluation of the location of stained neoplastic cells provide a more reliable estimate of biological aggressiveness than that obtained with histopathological patterns alone.