Phase II trial of estramustine phosphate and oral etoposide in patients with hormone-refractory prostate cancer.

BACKGROUND: There is a need for active agents with a better safety profile than docetaxel, yet good activity, for patients with hormone-refractory prostate cancer (HRPC). We carried out a phase II trial to determine the activity and safety of estramustine plus oral etoposide in HRPC. PATIENTS AND METHODS: Patients were given estramustine (280 mg twice daily) and etoposide (100 mg/day, days 1-21) in 28-day cycles until disease progression or unacceptable toxicity. Primary end points were overall response rate and safety, as determined by prostate-specific antigen (PSA) levels and lesion assessment. RESULTS: From November 2001 to February 2007, 75 patients were enrolled. All patients were assessable for safety; 17 (22.6%) had grade 3/4 toxicity. PSA response was assessable in 69, 14 of whom had a >50% reduction in PSA. Of 10 patients with one or more measurable lesions, two (20%) had partial response and two (20%) disease stabilization. Overall, median time to progression was 4.4 months (range 1 week-43 months); median survival was 23 months (range 3 weeks-64+ months). CONCLUSIONS: Estramustine plus etoposide is active and has a manageable safety profile in patients with HRPC. In asymptomatic patients with nonaggressive disease this combination could be useful to delay the start of more demanding treatments.

Vinorelbine-based chemotherapy in hormone-refractory prostate cancer.

BACKGROUND: No consensus exists regarding further therapy for the management of hormone-refractory prostate cancer. In this phase II study, the combination of Vinorelbine with 5-Fluorouracil and folinic acid (FLN regimen) was evaluated in patients with progressive or resistant disease after hormone therapy. PATIENTS AND METHODS: Thirty-four patients were treated with Vinorelbine at a dose of 20 mg/m2 intravenously (i.v.) on days 1 and 3, folinic acid (FA), 100 mg/m2 i.v. and 5-Fluorouracil (5-FU), 350 mg/m2 i.v. as a short infusion on days 1 to 3. The therapy was given in an out-patient setting, every 3 weeks. RESULTS: All of the 34 eligible patients were evaluable for toxicity and 30 for activity. A total of 127 cycles was administered (91% at full dose). Among thelS5 patients with measurable disease, four had a partial response (26.6%; C.I. 95%, 28.3% to 65.7%) and four achieved stable disease. In 14 patients (47%) a clinical benefit was documented. Six out of 15 patients with bone-only involvement had stable disease (40%). The median duration of stabilization and partial response was 16 weeks (range 4-24 weeks). The most common toxicity was hematological: Grade 4 (NCI-CTC scale) in five patients at re-cycle. Other toxicities were of low incidence and easy to manage. CONCLUSION: The encouraging results obtained with the FLN regimen in terms of clinical benefit and its predictable and manageable toxicity support the palliative role of this chemotherapeutic strategy in hormone-refractory prostate patients.

Gn-RH antagonist possible response, after Gn-RH agonist failure in a man with metastatic prostate cancer.

Gn-RH agonists or surgical castration are considered standard treatment for patients affected by metastatic prostate cancer. Despite greater cost, chemical castration is often considered the treatment of choice as it is psychologically better tolerated. We report our experience of one patient undergoing treatment with Gn-RH agonist who developed an early resistance to the administered drug, with serum testosterone levels within the range of normality.

Spermatic cord liposarcoma: a report of four cases.

Spermatic cord liposarcoma is a rare pathology (1-4); currently about one hundred cases are documented. The therapy of choice is surgery, followed sometimes by radiotherapy. We herein describe our experience of 4 cases between 1995 and 2000, with median follow-up of 34 months (mean 48 months, range 28-95 months), in order to stress the role of orchifuniculectomy, even when mass-ablation first procedure may seem radical.

Late solitary thyroid carcinoma metastasis to the kidney: a case report.

Secondary tumour to the kidney is quite frequent. Even if, theoretically, all solid tumours may give rise to renal metastasis, secondary lesions to the kidney occur more commonly in patients with lung and breast cancer, melanoma and lymphoma. Only 15 cases of renal metastasis arising from a follicular thyroid carcinoma have been reported in the literature. Rarely, metastases to the kidney present as primary renal tumours and may be treated surgically for that mistaken diagnosis. Nevertheless, in patients with solitary late distant metastasis of thyroid cancer, complete surgical resection may be proposed, followed by 131I ablation in order to offer a better chance of prolonged survival. We describe a case of a renal mass undergoing radical surgery and revealing itself as a solitary metastasis from follicular carcinoma of the thyroid, appearing 10 years after total thyroidectomy and 131I ablation therapy.

Correlation between pretreatment serum levels of neopterin and response to interleukin-2 immunotherapy in cancer patients.

IL-6 levels have been proven to correlate with resistance to IL-2 immunotherapy. Since IL-6 may be produced by both macrophages and TH2 lymphocytes, it is not possible to establish whether the negative prognostic significance of IL-6 levels may primarily depend on an enhanced macrophage or TH2 activation. Macrophage activation may be documented by the increase in its specific marker neopterin. In an attempt to establish whether the negative significance of IL-6 high levels prior to IL-2 immunotherapy may reflect an enhanced macrophage activation, we have investigated the relation existing between pretreatment concentrations of neopterin and response to IL-2 immunotherapy in cancer patients. The study included 20 metastatic renal cell cancer patients, who were treated with IL-2 subcutaneously at 6 million IU/day for 5 days/week for 6 weeks. Before the onset of IL-2 therapy, abnormally high serum levels of neopterin were seen in 11/20 patients. Moreover, neopterin concentrations were significantly correlated with those of IL-6. Tumor regression rate was significantly higher in patients with normal than in those with elevated levels of neopterin prior to therapy (5/9 vs 1/11, P < 0.05), as well as the percent of the survival at 1 year (9/9 vs 4/11, P < 0.01). This preliminary study would suggest that pretreatment values of the macrophage marker neopterin correlate with resistance to IL-2 cancer immunotherapy.

Lymphocytosis decline is not responsible for tumor progression in cancer patients chronically treated with interleukin-2.

AIMS AND BACKGROUND: The antitumor activity of IL-2 is mediated by an increase in lymphocyte number. Moreover, our previous studies have shown that therapy for 1 week/month with low-dose subcutaneous IL-2 is sufficient to maintain high levels of lymphocytes in cancer patient who have had tumor regression or stable disease (SD) in response to IL-2 immunotherapeutic cycles. This study was performed to establish whether tumor progression in cancer patients chronically treated with IL-2 may be associated with lymphocyte number decline. METHODS: The study included 53 metastatic renal cell cancer patients, who were treated with 2 induction cycles of IL-2 subcutaneous immunotherapy (6 million IU/day for 5 days/week for 6 weeks, corresponding to one cycle). Tumor regression occurred in 15/53 patients, 20 patients had a SD, and the remaining 18 cases progressed. Non progressed patients (n = 35) underwent a maintenance therapy consisting of one week of therapy every month. After a median follow-up of 18 months, 26/35 patients with response or SD had progressed. The immune investigation consisted of lymphocyte, T lymphocyte, NK cell number determination and sCD25 level detection. RESULTS: The mean number of lymphocytes, T lymphocytes and NK cells observed on IL-2 maintenance therapy was significantly higher than that seen before beginning the immunotherapy. Moreover, mean number of lymphocytes and mean levels of sCD25 observed at the time of tumor progression were respectively lower and higher than those seen on maintenance therapy in the same patients, without, however, significant differences. CONCLUSION: Despite the importance of lymphocytes in mediating the antitumor activity of IL-2, this study shows that tumor progression in cancer patients chronically treated with low-dose IL-2 after response or SD during IL-2 induction cycles is not associated with a significant decline in lymphocyte, T lymphocyte or NK cell numbers. Further studies, carried out to analyze the functional status of immune cells at the time of tumor progression, will be necessary to define the role of immunity in cancer patients progressing under IL-2 chronic therapy.

A randomized study of low-dose interleukin-2 subcutaneous immunotherapy versus interleukin-2 plus interferon-alpha as first line therapy for metastatic renal cell carcinoma.

AIMS AND BACKGROUND: IL-2 given subcutaneously in combination with interferon-alpha 2b (IFN) appears to induce a response rate comparable to that obtained with IL-2 intravenous injection in patients with metastatic renal cell carcinoma (RCC) but with lower toxicity. The role of IFN when combined with IL-2 has however still to be defined. The present study was performed to draw some preliminary conclusions about the effect of IFN in combination with IL-2 in metastatic RCC. METHODS: The study included 30 consecutive patients with metastatic RCC who were randomized to treatment with IL-2 subcutaneous therapy (3 million IU twice/daily for 5 days/week for 6 weeks) or with IL-2 plus IFN (5 million U/m2 subcutaneously thrice weekly). In patients without progressive disease, a second cycle was repeated after a 28-day rest period. RESULTS: No significant difference in partial response rate was found between patients treated with IL-2 alone and those given IL-2 plus IFN (5/15 vs 4/15). Similarly, no difference was seen in the percentage of stable disease (7/15 vs 7/15). Toxicity was higher in patients who received IL-2 plus IFN. Lymphocyte and eosinophil mean increase was higher in patients treated with IL-2 alone than in those treated with IL-2 plus IFN, without however any significant difference. CONCLUSIONS: The present results, which require confirmation in a larger series, indicate that combination with IFN does not increase the efficacy of IL-2 subcutaneous immunotherapy in metastatic RCC but only the toxicity of treatment.

[Immunotherapy with low-dose subcutaneous interleukin-2 in metastatic renal carcinoma]. / Immunoterapia con basse dosi di interleuchina-2 per via sottocutanea nel carcinoma renale metastatico.

The intravenous injection of interleukin-2 (IL-2) has appeared to induce tumor regression in metastatic renal cell carcinoma (RCC). IL-2 given subcutaneously has also appeared to be effective when it is administered in association with interferon-alpha (INF), but with a lower toxicity in comparison to the intravenous route of administration. The present study was carried out to evaluate the efficacy of a subcutaneous immunotherapy with IL-2 alone in metastatic RCC. The study included 30 consecutive patients affected by metastatic RCC, 14 of whom had been pretreated with INF plus vinblastine, while the other 16 patients received IL-2 as a first line therapy of their metastatic disease. IL-2 was given subcutaneously at a dose of 3 million IU twice/day for 5 days/week for 6 consecutive weeks, corresponding to one cycle of immunotherapy. No complete response was obtained. A partial response (PR) was achieved in 10/30 (33%) patients (median duration: 7 months, range 5-25), without any significant difference between patients pretreated with IFN and nonpretreated patients (4/14 vs 6/16). Response rate was significantly higher in nephrectomized patients than in those who did not undergo nephrectomy (10/25 vs 0/5; P < 0.01). Moreover, response rate was significantly higher in patients with performance status (PS) greater than 40% than in those with PS lower than 40% (10/23 vs 0/7; P < 0.01). A stable disease (SD) was obtained in 12/30 (40%) patients (median duration 5 months, range 3-13), while the remaining 8/30 (27%) progressed. The increase in lymphocyte and eosinophil mean number was significantly higher in patients with PR or SD than in the progressed ones.(ABSTRACT TRUNCATED AT 250 WORDS)

[Immunotherapy for metastatic renal carcinoma with interleukin-2 in a subcutanous administration schedule of short duration. Subcutaneous IL-2 in renal carcinoma]. / Immunoterapia del carcinoma renale metastatico con interleuchina-2 secondo uno schema di somministrazione sottocutanea di breve durata. IL-2 sottocutanea nel carcinoma renale.

It has been shown that low-dose subcutaneous (SC)IL-2 exerts an efficacy similar to that described for the intravenous high-doses in the immunotherapy of metastatic renal cell cancer (RCC). However, it remains to be established which could be the optimal duration of treatment. The most common schedules with subcutaneous IL-2 are generally consisting of 6 weeks of therapy, with an IL-2 dose of about 6 million IU/day. This study was performed to evaluate the efficacy of IL-2 subcutaneous immunotherapy with a duration of 4 weeks only. The study included 13 evaluable metastatic RCC patients. IL-2 has been injected subcutaneously at 6 million IU/day for 6 days/week for 4 weeks, by repeating a second cycle in nonprogressing patients after a 21-day rest period. Objective tumor regressions were achieved in 3/13 (23%) patients consisting of CR in 1 and PR in the other 2. Stable disease was obtained in other 6 patients. This preliminary study would suggest that a shorter dose-matched S.C.IL-2 immunotherapy may have a similar therapeutic efficacy in metastatic RCC. Therefore, the 4-week IL-2 S.C. immunotherapy, instead of the 6-week schedule could become the standard immunotherapeutic schedule, with following decreased cost and toxicity.

[Preoperative subcutaneous immunotherapy with interleukin-2 in renal carcinoma with synchronous metastasis: randomized clinico-biological study. Preoperative use of Il-2 in renal carcinoma]. / Immunoterapia sottocutanea preoperatoria con interleuchina-2 nel carcinoma renale con più sedi metastatiche sincrone: studio randomizzato clinico-biologico. IL-2 preoperatoria nel carcinoma renale.

Despite the efficacy of IL-2 in the treatment of metastatic renal cell carcinoma (RCC), the prognosis of patients with synchronous metastases still remains poor. Nephrectomy itself, as well as other surgical operations, may further suppress the antitumor immune response. Previous studies suggested that the preoperative injection of IL-2 may neutralize surgery-induced lymphocytopenia in advanced colon cancer. On this basis, a pilot randomized study was performed in an attempt to evaluate the effects of a preoperative administration of IL-2 on postoperative lymphocyte numbers and on the survival in advanced RVV patients with more than 3 synchronous metastases. The study included 20 consecutive patients, who were randomized to receive nephrectomy alone or nephrectomy plus preoperative subcutaneous immunotherapy with IL-2 (18 million IU/day for 3 days). Then, all patients underwent postoperative immunotherapy with IL-2 (6 million IU/day for 5 days/week for 6 weeks). Surgery-induced lymphocytopenia was completely abolished by IL-2 preoperative injection. The frequency of postoperative complications was significantly higher in controls than in patients preoperatively treated with IL-2. On the contrary, significant differences between control and patients preoperatively treated with IL-2 were observed neither in the clinical response to IL-2 immunotherapy, nor in the percent of 1-year survival. The results of this preliminary pilot study would suggest that IL-2 preoperative immunotherapy may neutralize surgery-induced lymphocytopenia and reduce the postoperative complications in RCC patients with synchronous metastases, without, however, influencing their prognosis in terms of survival time.

[Orthotopic ileal neobladders in men and women: techniques and comparison]. / Le neovesciche ileali ortotopiche nell'uomo e nella donna: tecniche a confronto.

PURPOSE: evaluation of results and complications of ileal orthotopic neobladders in men and women with transitional cell carcinoma. MATERIALS AND METHODS: between 12-89 and 12-95 we performed 146 radical cystectomy for bladder neoplasm, in 32 patients we can perform ileal orthotopic neobladder, 29 were male and 3 were female. Oncologic indications to this kind of operation were: clinical stage T2, T3a, T3b, T1G3 multicentric and or recurrence, absence of metastasis absence of nodal metastasis, negativity of urethral biopsy. General contraindications were urethral stenosis and incontinence. Oncological contraindications, in woman, were bladder neck neoplasm or urethral neoplasm. In 4 patients we use Camey II technique, in 19 pts we performed the paduan ileal neobladder, in 9 pts we use Hautmann technique. 7 patients performed neoadjuvant chemotherapy with 4 circles of MVAC, 4 pts underwent adjuvant chemotherapy, and 2 pts salvage chemotherapy. In woman we take care during cystectomy to dissect cardinal ligament very close to cervix uteri, to resect the uterosacral ligament far to the sacrum. We did not dissect under the ureter and we cut the urethra 0.5-1 cm far from the bladder neck. RESULTS: follow up was between 6 and 66 months. 24 patients are now alive and disease free, 2 patients are alive with disease progression, 1 have a pelvic recurrence and 1 have pulmonary recurrence. 4 pts died for disease progression and 2 for non oncological cause, quality of life was considered as regard to continence and sexual activity. 1 pts was completely incontinent and 1 pts has nocturnal incontinence with a daily micturation every 1 hour. We can evaluate only 18 patients for sexual activity and 4 reported normal erection. COMPLICATIONS: in three cases we had to reoperate for early complications due to mechanical bowel obstruction, ileocutaneous fistula and wound dehiscence. In three cases we had the formation of stones, in two patients ureteroileal stenosis, in two cases urethro-ileal stenosis and 1 reflux from the neobladder. Orthotopic ileal neobladder allows a very good quality of life and is the first choice derivation after radical cystectomy.

[Prognostic predictive factors of the clinical response to immunotherapy with subcutaneous interleukin-2, in patients with metastatic renal carcinoma: analysis of 60 cases]. / Fattori prognostici predittivi della risposta clinica alla immunoterapia con Interleuchina-2 per via sottocutanea, in pazienti con carcinoma renale metastatico (CRM): analisi di 60 casi.

The intravenous immunotherapy with high-dose interleukin-2 (IL-2) would constitute one of the most effective treatments of metastatic renal cell carcinoma (RCC). More recently, IL-2 subcutaneous therapy has also appeared active, either alone or in association with interferon, with results comparable to those found with the intravenous route of injection, but with a lower toxicity. On this basis, we have designed a protocol of treatment with low-dose IL-2 alone given subcutaneously as a first or a second line therapy in metastatic RCC. The study included 60 consecutive patients (pts) (M/F: 39/21, median age 56 years, range 26/74). IL-2 was given at a dose of 3 millions IU twice/day for 5 days/week, for 6 weeks, corresponding to one cycle. In non progressed pts a second cycle was repeated after a 28-day rest period. Dominant metastasis sites were, as follows: soft tissues: 8; bone: 11; lung: 29; liver: 3; liver plus lung: 7; adrenal: 2. The minimum follow-up was 18 months and the median follow-up was 34 months (range 18-48). A complete response (CR) was achieved in 2/60 (3%) pts. A partial response (PR) was obtained in 15/60 (25%). Therefore, tumor objective rate (CR + PR) was 17/60 (28%). The median duration of response was 13 months (4-33).(ABSTRACT TRUNCATED AT 250 WORDS)

[Lymphocyte levels before treatment with subcutaneous interleukin-2 and during maintenance treatment in relation to the clinical efficacy in metastatic renal carcinoma]. / Valori linfocitari pre-terapia con Interleuchina-2 sottocutanea e durante terapia di mantenimento in relazione all'efficacia clinica nel carcinoma renale metastatico.

AIMS AND BACKGROUND: the antitumor activity of IL-2 is mediated by an increase in lymphocyte number. Moreover, our previous studies have shown that therapy for 1 week/month with low-dose subcutaneous IL-2 is sufficient to maintain high levels of lymphocytes in cancer patients who have had tumor regression or stable disease (SD) in response to IL-2 immunotherapeutic cycles. This study was performed to establish whether tumor progression in cancer patients chronically treated with IL-2 may be associated with lymphocyte number decline. METHODS: the study included 60 metastatic renal cell patients, who were treated with 2 induction cycles of IL-2 subcutaneous immunotherapy (6 million IU/day for 5 days/week for 6 weeks, corresponding to one cycle). Tumor regression occurred in 17/60 patients, 23 patients a SD, and the remaining 20 cases progressed. Non-progressed patients (n = 40) underwent a maintenance therapy consisting of one week of therapy every month. After a median follow-up of 18 months, 29/40 patients with response or SD had progressed. The immune investigation consisted of lymphocyte, T lymphocytes, NK cell number determination and sCD25 level detection. RESULTS: the mean number of lymphocytes, T lymphocytes and NK cells observed on IL-2 maintenance therapy was significantly higher than that seen before beginning the immunotherapy. Moreover, mean number of lymphocytes and mean levels of sCD25 observed at the time of tumor progression were respectively lower and higher than those seen on maintenance therapy in the same patients, without, however, significant differences. CONCLUSION: despite the importance of lymphocytes in mediating the antitumor activity of IL-2, this study shows that tumor progression in cancer patients chronically treated with low-dose IL-2 after response or SD during IL-2 induction cycles is not associated with a significant decline in lymphocyte, T lymphocyte or NK cell numbers. Further studies, carried out to analyze the functional status of immune cells at the time of tumor progression, will be necessary to define the role of immunity in cancer patients progressing under IL-2 chronic therapy.

[Clinical response and survival in metastatic renal carcinoma during subcutaneous administration of interleukin-2 alone. Subcutaneous Il-2 in renal carcinoma]. / Risposta clinica e sopravvivenza nel carcinoma renale metastatico durante somministrazione sottocutanea di sola interleuchina-2. Il-2 sottocutanea nel carcinoma renale.

Several clinical studies have demonstrated the efficacy of subcutaneous immunotherapy with Il-2 alone in metastatic renal cell carcinoma (RCC). In an attempt to better define the clinical parameters which may predict the efficacy of treatment, the present study shows the results obtained with subcutaneous Il-2 alone in 91 evaluable metastatic RCC patients. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days/week for 6 weeks, corresponding to one immunotherapeutic cycle. In nonprogressing patients, a second cycle was given after 28-day rest period. A complete response (CR) was achieved in 2/91 patients. Moreover, 19/91 patients had a partial response (PR). Therefore, objective response (OR) rate was 21/91 (23%) patients. Stable disease (SD) was achieved in 41 patients, while the remaining 29 patients had a progressive disease (PD). OR rate was significantly higher in patients with a long disease-free survival than in patients with synchronous metastases, in nephrectomized patients than in the non-nephrectomized ones, and in patients with high than in those with low PS. The survival obtained in patients with CR or PA was significantly longer with respect to that found in patients with SD or PD. The toxicity was substantially low in all patients. This study confirms that the subcutaneous immunotherapy with IL-2 alone is an effective and well tolerated therapy of metastatic RCC.

[Results of calcitonin therapy of the painful symptoms caused by osteolytic metastases of prostatic carcinoma]. / Risultati della terapia con calcitonina sulla sintomatologia dolorosa da metastasi osteolitiche di carcinoma prostatico.

Albeit within the limits imposed on us by the restricted number of cases, we can state that--in the present state of research--calcitonin constitutes a useful complement in treatment of osteolytic metastasis induced by carcinoma of the prostate. Is utilisation is justified by the effects observed: on the one hand, osteogenesis as a factor protecting against the aggressivity of the tumoural cells, and on the other the considerable antalgic strength allied with improvement in the calcium, phosphorus and phosphatase values. For some time we have replaced pig calcitonin with salmon calcitonin: the comparative results with this second product will be the subject of a subsequent paper.

Local staging of penile cancer using magnetic resonance imaging with pharmacologically induced penile erection.

PURPOSE: This study was undertaken to compare the local staging of penile cancer by magnetic resonance imaging (MRI) combined with pharmacologically induced penile erection (PIPE), with clinical examination and pathology, and to verify whether MRI-PIPE led to changes in treatment planning in our cohort. MATERIALS AND METHODS: Thirteen patients with untreated penile cancer underwent local staging by clinical examination and MRI-PIPE obtained by intracavernosal injection of 10 mug prostaglandin E1. Transverse, sagittal and coronal T2-weighted and T1-weighted (before and after intravenous gadolinium injection) images were obtained with a four-channel phased-array coil. Tumours were treated according to stage, as defined by MRI-PIPE and clinical examination. Stage T1 tumours underwent laser ablation and stage T2 or T3 tumours partial or total penectomy. RESULTS: Twelve penile cancers were squamous cell carcinomas and one was a sarcoma. MRI-PIPE correctly staged 12 out of 13 patients, failing to detect one in situ carcinoma. Clinical examination correctly staged eight out of 13 patients, over-staging two patients (one Tis was over-staged as T1 and one T1 as T2) and under-staging three patients (two T2 as T1 and one T3 as T2). CONCLUSION: MRI-PIPE performed better than the clinical examination and changed treatment planning in three patients.

Generation of species cross-reactive aptamers using "toggle" SELEX.

Species cross-reactivity facilitates the preclinical evaluation of potentially therapeutic molecules in animal models. Here we describe an in vitro selection strategy in which RNA ligands (aptamers) that bind both human and porcine thrombin were selected by "toggling" the protein target between human and porcine thrombin during alternating rounds of selection. The "toggle" selection process yielded a family of aptamers, all of which bound both human and porcine thrombin with high affinity. Toggle-25, a characteristic member, inhibited two of thrombin's most important functions: plasma clot formation and platelet activation. If appropriate targets are available, the toggle strategy is a simple measure that promotes cross-reactivity and may be generalizable to related proteins of the same species as well as to other combinatorial library screening strategies. This strategy should facilitate the isolation of ligands with needed properties for gene therapy and other therapeutic and diagnostic applications.

[Recurrence of acute lymphoid leukemia in the bladder: a rare cause of bilateral hydronephrosis]. / Recidiva di leucemia linfoide acuta a livello vescicale: una rara causa di idronefrosi bilaterale.

While the invasion of the bladder by neoplastic cells during acute lymphatic leukaemia in children has been reported by various authors, the leukaemic invasion of the bladder in adults is extremely rare. We report a case of recurrence of A.L.L. in the bladder presenting colicky symptomatology and obstruction of the excretory tracts.

Paradoxical stimulation of prolactin secretion by L-dopa in metastatic prostate cancer and its possible role in prostate-cancer-related hyperprolactinemia.

OBJECTIVE: In addition to sex steroids, prolactin (PRL) may also stimulate prostate cancer growth. Abnormally high blood levels of PRL have been noted in metastatic prostate cancer patients. However, most studies have been limited to the evaluation of basal levels of PRL rather than to investigate its secretion in response to classical endocrine dynamic tests. This study was carried out to analyze PRL secretion in metastatic prostate cancer patients both at basal conditions and in response to L-Dopa and metoclopramide, which represents the most classical inhibitory and stimulatory tests for PRL secretion, respectively. METHODS: The study included 12 patients with metastatic prostate cancer. On separate occasions, PRL secretion was evaluated in response to L-Dopa (500 mg orally) and to metoclopramide (10 mg i.v. as a bolus). Serum levels of PRL were measured by RIA. RESULTS: Mean PRL concentrations significantly increased after metoclopramide administration, even though no PRL response occurred in 6 of 12 patients. L-Dopa was unable to reduce PRL levels, which, in contrast, paradoxically significantly increased in response to L-Dopa, with mean values comparable to those achieved after metoclopramide injection. CONCLUSION: By showing a paradoxical stimulatory effect of L-Dopa on PRL secretion and a lack of response to metoclopramide in some patients, this study would suggest the existence of evident alterations in the neuroendocrine regulation of PRL release in advanced prostate cancer.