Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

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

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

Long-term immunotherapy with low-dose interleukin-2 and interferon-alpha in the treatment of patients with advanced renal cell carcinoma.

BACKGROUND: The objective of this study was to evaluate response, toxicity, and immunologic effects of an original immunotherapy schedule based on repeated cycles of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFNalpha) in patients with metastatic renal cell carcinoma (mRCC). METHODS: Fifty patients who underwent nephrectomy received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFNalpha twice weekly for 4 consecutive weeks. The cycle was regularly repeated indefinitely at 4-month intervals in all patients, irrespective of their response. rIL-2 (1 x 10(6) IU/m(2)) was administered every 12 hours on Days 1 and 2 and once per day on Days 3-5 of each week; rIFNalpha (1.8 x 10(6) IU/m(2)) was given on Days 3 and 5. Toxicity was graded according to the World Health Organization (WHO) criteria. Forty percent of the patients had only one metastatic disease site at the time of treatment. The Kaplan-Meier method was used to estimate survival, and an analysis of variance was used to evaluate the effects on leukocytes and lymphocyte subsets over time. RESULTS: A total of 241 cycles were administered. One patient achieved a complete response, and five patients achieved a partial response. Five patients had stable disease, and 30 patients had progressive disease. Nine patients were not evaluable for response. The overall response rate was 12% (95% confidence interval, 3-21%) on the basis of an intent-to-treat analysis. The 36-month survival probability for all 50 patients was 47%. Treatment-related toxicity was limited to WHO Grades 1 and 2. Both lymphocyte and eosinophil levels significantly increased after all cycles (by 42% and 353%, respectively). The treatment also induced significant increases in the CD25 positive (24%), CD56 positive (28%), and CD3 negative/CD56 positive (54%) lymphocyte subsets. CONCLUSIONS: Long-term, repeated treatment with low doses of rIL-2 and rIFNalpha is feasible in patients with mRCC. The schedule induces clinical response rates and survival probabilities are similar to those obtained using higher doses.

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

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

Effectiveness of very low doses of immunotherapy in advanced renal cell cancer.

Twenty-one nephrectomized patients with metastatic renal cell cancer were treated with recombinant interleukin 2 (rlL-2) and interferon alpha (rIFN alpha). rIL-2 was administered s.c. at a dose of 1 x 10(6) IU m(-2) every 12 h on days 1 and 2, followed by 0.5 x 10(6) IU twice daily on days 3-5; rIFN alpha-2 was given i.m. as 1.8 x 10(6) IU m(-2) on days 3 and 5 of each week for 4 consecutive weeks. The cycle was regularly repeated at 4-month intervals and continued ad libitum in patients showing some response and in patients with progressing disease. Of 20 patients evaluable for treatment response, one (5%) had a complete response and three (15%) showed partial response. Three patients (15%) achieved stable disease and 13 (65%) were evaluated as having progressive disease. The estimated actuarial 44-month survival rate was 44%. Toxicity was limited to WHO grades 1 and 2 only.

Action of pirenzepine on the human urinary bladder in vitro.

The novel compound pirenzepine was tested for its antimuscarinic effect on the human urinary bladder "in vitro." Its behavior towards the contractions induced by acetylcholine or bethanechol and towards electrically induced contractions was identical to that of atropine. However, its potency was 100 to 300 times lower than that of atropine. Results obtained with ganglion blocking agents, tetrodotoxin and cooled preparations of urinary bladder seem to indicate the virtually total absence of ganglionic cells. On the other hand they point out the fundamental role of post-synaptic muscarinic M2 receptors as the most important component of the cholinergic system in the bladder. Of course the existence of other transmitters released at the cholinergic nerve endings after electrical field stimulation cannot be excluded on the basis of our experiments.

[Vesico-renal reflux caused by neurogenic bladder from spina bifida in childhood]. / Il reflusso vescico renale secondario a vescica neuropatica da spina bifida in età pediatrica.

The authors report their experience related to 35 cases of neuropathic bladder examined during the last 12 months. They discuss the method followed for the study of each patient. Particularly they underline the importance of: scintiscan in the valuation of the renal function and urodynamic tests for a better knowledge of vesical disfunction. In the patient with vesicorenal reflux they propose two kinds of treatment (medical or surgical), selected after a complete valuation of radiologic, functional and urodynamic tests. They underline the importance of the pharmacological treatment, single or associated with surgical operation, in the patients with reflux and with a low vesical compliance and/or hyperreflexic bladder. Finally the Authors discuss the antireflux surgical techniques that they prefer and that have consented them to obtain excellent results.

[Epidermoid cysts of the testis: conservative treatment?]. / La cisti epidermoide del testicolo: trattamento conservativo?

The epidermoid cyst of the testis is a monolayer teratoma with no malignant character, when pure. Therefore, its recognition on the basis of macroscopic and freeze histologic grounds should allow a conservative surgical removal, with saving of the testis. Out of the more or less 150 reported cases, about 85% have been treated by orchiectomy, about 15% by either enucleation or partial orchiectomy. In no case except one, a more thorough histologic examination of the removed cyst, malignant structures have been observed. In no case, with a follow-up from a few months to more than 15 years, a recurrence occurred. Two cases are presented and discussed, in which a conservative choice was made and clinical follow-up carried out.

Use of strain gauge plethysmography in the study of varicocele.

The clinical significance of strain gauge plethysmography in pampiniform plexus pathology has been explored, with the assumption that there should be some analogy with lower limb venous conditions in which this examination gives valuable results. The first findings seem to confirm that strain gauge plethysmography affords, in varicocele, some reliable evaluations on venous drainage insufficiency, capacity and resiliency of spermatic venous bed as well as on functional results of surgical treatment.

Effects of rociverine on the human ureter: in vivo and in vitro experimental study.

An in vitro and in vivo study was conducted to verify the effects of rociverine--a new spasmolytic agent--on peristalsis in the human ureter. In vitro (human ureter strips), rociverine exerted a spasmolytic activity both on the baseline motility and on the spasm induced by direct contractants (eledoisin, KCl) or by histamine. It may therefore be concluded that rociverine is a predominantly myotropic spasmolytic. In the in vivo study, conducted in patients with cutaneous ureterostomy, the drug showed a marked inhibitory effect on the amplitude and frequency of the ureteral rhythmic spikes, without affecting the baseline tone.

Pseudomyotonia of the striated urethral sphincter.

Pseudomyotonic discharges of the striated urethral sphincter are infrequent findings. We herein report on 9 patients with dissimilar anatomical-clinical conditions. In some patients a definite neurological lesion was ascertained, whereas in the remaining patients no neurological impairment could be determined clinically and instrumentally. The possibility of spontaneous resolution of the phenomenon is an interesting clinical feature.

Histamine receptors in the human ureter.

The occurrence of histamine H1- and H2-receptors in the human ureter was studied by means of relatively selective agonists and antagonists of both kinds of receptors. Isolated preparations of small strips of human ureters removed during surgery were used. Histamine and the H1-agonist 2-aminoethylthiazole contracted the ureter in a dose-dependent fashion whereas the H2-agonists dimaprit and impromidine were ineffective. The H1-antagonist chlorpheniramine shifted to the right the dose-response curves to histamine and to 2-aminoethylthiazole with the kinetics of the competitive antagonism. Conversely the H2-antagonists cimetidine, metiamide and tiotidine potentiated the effect of histamine by a factor of 3 though high concentrations had to be used (25 - 30 micrograms/ml). Both H1 and H2-antagonists were not able to modify the basal tone and/or motility showed by ureteral strips. All the above data suggested that H1-receptors are predominant in the human ureteral muscle and the contraction induced by their stimulation completely mask the effect of the H2-receptors stimulation. Since H2-agonists were ineffective in basal conditions and H2-antagonists potentiated the effect of histamine which is spasmogenic, we may suggest that H2-receptors are less numerous than H1-receptors and their stimulation cause a slight relaxation of the ureteral muscle. This situation is not uncommon in other smooth muscle system (e.g. respiratory system and gastrointestinal tract).

[Multicystic dysplasia of the kidney in the adult]. / Diplasia multicistica del rene nell'adulto.

Two cases of multicystic renal dysplasia in the adult are presented and the pathogenic theories of the condition are reviewed. The more severe defects of development are those which more often remain clinically silent, until are detected, usually in a casual manner, in the adult age. Palpable mass or, more often, traditional radiology, densito-tomography and echography allow differentiation from other conditions such as polycystic kidney, tumors, tuberculosis, hydronephrosis. Anyhow, in the Author's opinion, surgical exploration is mandatory for definite diagnosis as well as for exeresis of the dysplastic mass.

[Urodynamic assessment in multiple sclerosis and Parkinson's disease]. / La valutazione urodinamica strumentale nella sclerosi multipla e nel morbo di Parkinson.

Twenty five patients with C.N.S. diseases (parkinsonism and multiple sclerosis) have been studied by means of electrocystouretromanometry and electromyography. Cases with patent urological causes of vesico-sphincteric functional impairment have not been included. In multiple sclerosis urodynamic changes, chiefly detrusor hyper-reflexia, have been registered in 75% of cases, EMG sphincter activity disturbances in 85%. Respectively, 90% of cystomanometries and 54% of EMG sphincter activities showed changes in Parkinsonism. The precise assessment of the individual specific urodynamic change seems to allow a rationally better therapeutic perspective.

[Urodynamic evaluations after abdomino-perineal resection of the rectum (author's transl)]. / Valutazioni urodinamiche dopo interventi di amputazione del sigma-retto per via addomino-perineale.

An uro-dynamic evaluation has been performed on 25 patients, who had been submitted to abdomino-perineal amputation of the rectum and had thereafter shown functional disturbances of micturition. On the latter, causes and mechanisms are discussed, particularly neurological as well as mechanical and inflammatory ones, with regard to their relationship with sex and other possible aspects in the field of pathology. In 16 cases urinary retention developed, in 4 cases urinary incontinence, in 4 cases urgency but complete voiding. The authors conclude by stressing the role of pre-operative uro-dynamic assessment in every patient who is going to be submitted to rectal exeresis, in order to detect sub-clinical functional impairment of micturition, which could be suitably treated, during the main operation itself, by either desobstructive or reconstructive measures.