Basal plasma levels of calcitonin and bone mineral mass in normal and uremic women. Effect of menopause.

Basal plasma levels of immunoreactive calcitonin (iCT), forearm bone mineral content (BMC) as measured by 125I photon absorptiometry and 24-hour urinary hydroxyproline/creatinine ratio (OHPr/Cr) were determined in 32 healthy women (13 pre-menopausal, aged 40 to 54 years, and 19 post-menopausal, aged 41 to 54 years). The basal plasma levels of iCT were significantly higher in the pre-menopausal group (mean value 96 vs 54 pg/ml, P less than 0.025). The BMC value of the radius was also significantly greater in the same group (mean +/- SEM 656 +/- 13 vs. 620 +/- 9 mg/cm2, P less than 0.05), while the urinary OHPr/Cr ratio was higher in the post-menopausal group (29.9 +/- 1.5 vs. 38.7 +/- 2.7 mg/g, P less than 0.02). These results suggest that basal plasma levels of iCT decrease after the menopause and support the hypothesis that a deficiency of CT could be involved in the pathogenesis of post-menopausal bone loss. Similar results were obtained in 25 uremic women on maintenance hemodialysis (9 pre-menopausal and 16 post-menopausal) aged 30 to 65 yrs.: both basal iCT levels and BMC values were significantly higher in the pre-menopausal group.

Prevention of glucocorticoid-induced osteopenia: effect of oral 25-hydroxyvitamin D and calcium.

Twenty-four patients (9 M and 15 F, age range 51-82) with polymyalgia rheumatica receiving 6-methylprednisolone for a period of 9 months (16 mg/daily/two weeks, 14 mg/daily/two weeks, 12 mg/daily/1 month, 10 mg/daily/1 month, 8 mg/daily/1 month, 6 mg/daily/1 month and 4 mg/daily for the last four months) were randomly assigned to receive either 250HD3 (35 mcg/day for 25 days/month) (Group A) or placebo (Group B) in a double-blind study. All patients also received 500 mg elemental calcium daily. Before and at 3, 6 and 9 months ESR, tenderness on palpation and subjective pain were evaluated. At the same times, mineral metabolism parameters (serum calcium, phosphorus, alkaline phosphatase, 24-h urinary calcium, phosphate and 24-h hydroxyproline excretion) and radial bone mineral content (BMC) were evaluated. Activity indexes (ESR and clinical parameters) improved in both groups. Furthermore, serum alkaline phosphatase and 24-h hydroxyproline excretion decreased significantly only in Group A, and BMC decreased significantly in Group B but rose slightly in Group A. No side effects were observed in any of the patients.

[Anatomy of the urethral sphincteric vesico-prostatic complex]. / Anatomia del complesso sfinterico vescico-prostatico uretrale.

As 27 different names have been proposed for the components of the urethral sphincter, it is difficult to build a clear anatomical model of it. Starting from a review of the literature and from some personal observations of surgical anatomy, our aim is to draw a vision as much organic as possible of the anatomy of the urethral sphincter. The components of the urethral sphincter are: the bladder neck (preprostatic sphincter), the smooth muscle urethral sphincter, the rhabdosphincter and levator ani muscle. Recently the rhabdosphincter has been proposed as a vertical structure that extends from the pelvic cavity (bladder base) to the perineal cavity. It can be round-shaped or omega-shaped. The anterior insertions are along the anterolateral aspect of the prostate (superiorly) and on the perineal fascia (inferiorly). The posterior insertions are on the Denonvilliers fascia and posterior aspect of the prostatic apex (superiorly) and on the central perineal tendon (inferiorly). The rhabdosphincter has strong means of fixations: anteriorly it is fixed to the pubis by the pubo-urethral ligaments, posteriorly it is supported by the medial fibrous raphe of the perineum. The anteromedial fibres of levator ani muscle are involved in the continence mechanism by their strong relation with the rhabdosphincter and the prostate.

[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.

[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.

[Personal research: reconstruction of the urethral striated sphincter]. / Ricerca personale: la ricostruzione dello sfintere striato uretrale.

OBJECTIVE: Incontinence is one of the drawbacks of radical prostatectomy. The causes of post-operative incontinence are sphincter deficiency (SD) and bladder dysfunction (BD). SD seems to be the main cause of incontinence and long time to continence. We present a surgical modification of the anatomical radical retropubic prostatectomy consisting in the reconstruction of the posterior aspect of the striated urethral sphincter in order to obtain a quick recovery of continence postoperatively. MATERIALS AND METHODS: Caudal retraction of the urethro-sphincteric complex after apical dissection of the prostate often occurs. Furthermore posterior fibrous raphe interruption can cause shortening of anatomical and functional urethral length and affect continence. In order to avoid caudal retraction of the sphincteric complex, after completing vesico-urethral anastomosis, the posterior emicircumference of the striated sphincter is fixed to the posterior aspect of the bladder one centimeter cranially and posteriorly to the urethro-vesical anastomosis. The rabdosphincter is sutured separately from the urethro-vesical suturing. This technical modification makes it possible to obtain an anatomical length of the urethra of about a centimeter more than with the standard technique, replacing it in a more anatomical position. Furthermore, this technique provides the new posterior platform for the urethro-sphincteric complex. Twenty-four patients with clinical organ confined disease and age range 54-74 years (mean 64 years) underwent Walsh's anatomical radical retropubic prostatectomy with reconstruction of the rabdosphincter (group A). Catheter was removed 7 to 11 days postoperatively. Early continence was assessed objectively with the number of pads per day as follows: 0-1 mini pad = continent; 1-2 pads per day = mild incontinence; 2 or more pads per day = severe incontinence. Continence was evaluated at 3 days and one month after catheter removal. Group A compared to 21 patients (group B) who underwent standard anatomical RPP (historical control group). RESULTS: In group A 16/24 patients (66.7%) and 19/24 patients (79.2%) were continent respectively at three days after removal of the catheter and after one month; mild incontinence (1-2 pads/day) was present in 6/24 patients (25%) and 3/24 (12.5%) respectively, 2/24 patients (8.3%) suffered from severe incontinence after 3 days and one month. In group B 7/21 patients (33%) were continent at hospital discharge, 11/21 (52%) after one month. CONCLUSIONS: Careful reconstruction of the posterior aspects of the rabdosphincter shortens time to continence after RRP.

[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.

Singh's method of the radiological quantitative evaluation of osteoporosis compared with the densitometric method.

The quantitative evaluation of osteoporosis by Singh's radiographic method, which is based on analysis of the trabecular pattern of the upper end of the femur, recognises seven successive grades of bone loss. This method has been shown, by comparison with bone densitometry, to be reliable both for the quantification of osteoporosis and as a screening method for early diagnosis. The method is sufficiently precise, and is not affected by independent factors such as variations of radiographic technique and the individual characteristics of the subject being tested.

Gangliosides released by the perfused rat liver are associated to high density lipoprotein.

We examine here the delivery of gangliosides from the perfused rat liver into the perfusate. One hour after the administration of [3H]GM1 to recirculating perfused livers, almost 80% of the perfusate radioactive gangliosides were recovered associated to the HDL fraction. This fraction was relatively enriched in radioactive GD1a. The pattern of endogenous gangliosides from perfused livers, rat serum and perfusates were very different: GM3 was the main liver ganglioside, GM1 and GD1a were the most abundant in perfusates being GM3 almost absent; GM3, GM1 and GD1a were present in rat serum in similar proportions. Using a non-recirculating perfusion protocol, radioactive gangliosides were found in the HDL fraction since 15 minutes after the administration of [3H]GM1. These results suggest that rat liver supplies the perfusates with some gangliosides and that they are associated to HDL. These facts arise the possibility that the liver is one of the source of serum gangliosides.

[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.

Synergic interactions of macrolides and proton-pump inhibitors against Helicobacter pylori: a comparative in-vitro study.

Thirty-eight clinical strains of Helicobacter pylori were isolated from patients with chronic gastritis and gastroduodenal ulceration, and their susceptibility to macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin) in combination with proton-pump inhibitors (lansoprazole and omeprazole) and bismuth subcitrate was assayed. Chequerboard titration was used to analyse the results of antimicrobial interactions and showed that the activity of macrolides was enhanced by combining them with lansoprazole, omeprazole or, to a lesser extent, bismuth subcitrate. While the interactions between erythromycin and the proton-pump inhibitors or bismuth subcitrate were always additive, the combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H. pylori strains, respectively. These results may, in part, account for the enhanced clinical efficacy of macrolides administered with proton-pump inhibitors in the treatment of H. pylori-associated diseases.

[New surgical classification of renoureteral lithiasis]. / Nueva clasificación quirúrgica de la litiasis renoureteral.

The authors suggest a change in their surgical classification of renal calculi to conform the description to the new techniques in the treatment of renal calculosis. Category "C" describes the morphology and topography of renal stones in five degrees (C1-C5); small letters "p", "s", "m", "i" indicate the pelvis, superior, middle, inferior calyces; "n" and "a" symbolize a stone having a size similar to or exceeding normal shaped renal cavities. "Cu" indicates ureteral calculi; small letters, "l", "i", "p" indicate lumbar, iliac, pelvic ureteral stones. "N" describes the nature of the calculi. Category "E" stands for the excretory tract: "+" and "-" indicate the presence or absence of dilatation; the small letters "e", "i" show the extra or intrarenal position of renal cavities; "no" and "o" indicate absence or presence of intrinsic obstruction of the excretory tract. "R" points out the number of surgical recurrences. Category "P" indicates the function of the parenchyma; numbers 1, 2, 3 refer to normal renal function, moderate or serious insufficiency. "U" stands for unique functional or anatomical kidney; "I" indicates the presence of infection.

Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role.

The antiinflammatory activity of a new 14-membered macrolide antibiotic, roxithromycin, was evaluated in various rat models including carrageenan- and poly-L-arginine-induced hind-paw oedema, croton oil inflamed ear assay and polyester sponge granuloma. When administered orally to animals, roxithromycin displayed an atypical profile in the assays utilized, including: (1) marked antioedema activity similar to that of indomethacin in poly-L-arginine assay, (2) significant inhibition of lambda-carrageenan hind-paw oedema and croton-oil-induced inflammation in the ear, although indomethacin was more effective, and (3) failure to reduce the development of granuloma induced by implanted polyester sponges, while indomethacin significantly reduced the chronic inflammatory reaction. Based on these results, it is concluded that roxithromycin is active in reducing the acute inflammatory reaction in rat models through mechanisms different from conventional nonsteroidal antiinflammatory agents such as indomethacin. Therefore, roxithromycin may have a favorable impact on skin inflammatory reactions accompanying microbial infections.

In vitro and ex vivo effect of tiaprofenic acid on human peripheral blood mononuclear cells.

The effect of the non-steroidal anti-inflammatory drug (NSAID) tiaprofenic acid on different human immune parameters was investigated in vitro or following in vivo administration in healthy adult volunteers. Results from the in vitro study demonstrated an increased mitogen-induced blastogenesis and interleukin 2 (IL-2) production together with a reduced polyclonal immunoglobulin (Ig) secretion in the presence of the drug. Results from the ex vivo study showed that treatment with tiaprofenic acid had no significant effects on the immune parameters investigated, i.e. unstimulated and mitogen-induced proliferation and IL-2 production, spontaneous and stimulated Ig synthesis, lymphocyte subpopulations, serum Ig and complement levels.

Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling.

Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell-cell and cell-extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-beta]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-alpha in the presence of different concentrations (0.01-100.0nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (p<0.05), whereas TNF-alpha induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (p<0.05, each comparison). No changes in HCAM expression and in TGF-beta release were observed (p>0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release (p<0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release (p<0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-beta release (p>0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.

[A new classification of reno-ureteral lithiasis]. / Nuova classificazione della litiasi reno-ureterale.

The Authors suggest a change in their surgical classification of renal calculi to conform the description to the new techniques in the treatment of renal calculosis. Category "C" describes the morphology and topography of renal stones in five degrees (C1-C5); small letters "p, s, m, i" indicate the pelvis, superior, middle, inferior calyces; "n" and "a" symbolize stone having a size similar to or exceeding normal shaped renal cavities. "Cu" indicates ureteral calculi; small letters "l, i, p" indicate lumbar, iliac, pelvic ureteral stones. "N" describes the nature of the calculi. Category "E" stands for the excretory tract; "+" and "-" indicate the presence or absence of dilatation, the small letters "e, i" show the extra or intrarenal position of renal cavities; "no" and "o" indicate absence or presence of intrinsic obstruction of the excretory tract. "R" points out the number of surgical recurrences. Category "P" indicates the function of the parenchyma; numbers 1, 2, 3, refer to normal renal function, moderate or serious insufficiency. "U" stands for unique functional or anatomical kidney; "I" indicates the presence of infection.

[Neoadjuvant chemotherapy using cisplatin (CDDP) and methotrexate (MTX) in carcinoma of the bladder]. / Chemioterapia neoadiuvante con cisplatino (CDDP) e methotrexate (MTX) nel carcinoma della vescica.

From June 1986 to November 1989, 7 patients (pts.) with transitional bladder cancer were treated with CDDP 70 mg/m2 i.v. on day 1 and MTX 40 mg/m2 i.v. on days 8 and 15. The initial stage was T2 N0 M0 (2), T2 N0 M0 (8), T4 N0 M0 (4) and T3-4 N+ M0 (3). The median age was 56 years. After a median number of two cycles (1-5) of CDDP-MTX, 3/17 pts. (17.6%) had a complete remission (CM), 9/17 pts. (53%) a partial response (PR) greater than 50%, 4/17 pts. (23.4%) a PR less than 50%, 1/17 pts. (6%) a stable disease. Nausea and vomiting occurred in almost all pts., 20% of pts. had grade 3 stomatitis, 35% of pts. had diarrhoea, 20% of pts. had conjunctivitis, 7% of pts. had a bone marrow depression and hair loss. One patient had severe renal and liver toxicity and grade 4 bone marrow suppression with sepsis, completely controlled after intensive care. The treatment after neoadjuvant chemotherapy was: radical cystectomy (11)- in one following radiotherapy -; partial resection + lymphoadenectomy (2); TUR (4) in 1 pt. with lymphoadenectomy. After a median follow-up of 28 months (6-36), 12/17, equivalent to 71% of pts. are disease free, 3/17 (17%) are alive with disease, 2/17 (12%) died. In conclusion the association of neoadjuvant CDDP-MTX can induce a high percentage of response, and can preserve bladder function in some patients. Further controlled trials and a longer follow-up are needed to better define the exact role of this combination in terms of disease free survival, total survival and quality of life.