Allogeneic gene-modified tumour cells in metastatic kidney cancer. Preliminary report.

An allogeneic irradiated RCC cell line, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells, was used to vaccinate ten MRCC patients in progression of disease in spite of IL-2 immunotherapy. The cells were administered subcutaneously and/or intra-tumourally. Sixty-four MRCC patients in progressive disease, not treated by vaccination but receiving similar IL-2 immunotherapy, were considered as the control group. Patients received 4-16 injections (mean 9 +/- 4), containing an average of 10.6 x 10(7) +/- 7.7 x 10(7) ACHN-IL-2-transfected cells (a minimum of 4 x 10(7), and a maximum of 31 x 10(7)). Four patients also received intra-tumour injections. Vaccination was administered during 30-418 days, and the follow-up continued for 649 +/- 353 days (190-1342). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were observed. One complete and one partial tumour response were observed, as well as two stable and one no-relapse disease. All but one patient died. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. In spite of the small number of treated patients, Wilcoxon's test showed a significant (P < 0.05) improvement of the survival in the vaccinated group compared to that of the control. The described vaccination protocol seems safe, devoid of adverse side effects and promising. It warrants further investigation.

Immunotherapy of metastatic kidney cancer.

From April 1986 to September 2000, 122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 x 10(6) LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n = 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n = 11) and PR (n = 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing low-dose immunomodulatory treatments.

Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses.

Forty-four patients suffering from genital (22) and labial (22) herpes were orally treated with HSV-1/2-specific transfer factor (TF). TF was obtained by in vitro replication of a HSV-1/2-specific bovine dialysable lymphocyte extract. Treatment was administered bi-weekly the first 2 weeks, and then weekly for 6 months, most patients received 2-3 courses. The total observation period for all patients before treatment was 26,660 days, with 544 relapses, and a relapse index of 61.2, whereas the cumulative observation period during and after treatment was 16,945 days, with a total of 121 relapsing episodes and a cumulative RI of 21.4 (P < 0.0001). Results were equally significant when the 2 groups of patients (labial and genital) were considered separately. These observations confirm previous results obtained with bovine HSV-specific TF, and warrant further studies to establish HSV-specific TF as a choice of treatment for preventing herpes recurrences.

A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer.

As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA). These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one intramuscular injection of 2-5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was 126 weeks, higher than the survival rates reported in the literature for patients of the same stage.

Use of transfer factor for the treatment of recurrent non-bacterial female cystitis (NBRC): a preliminary report.

Results of conventional treatment of female non-bacterial recurrent cystitis (NBRC) are discouraging. Most patients show an unexpected high incidence of vaginal candidiasis, while their cell mediated immunity to Herpes simplex viruses (HSV) and Candida antigens seems impaired, and it is known that the persistence of mucocutaneous chronic candidiasis is mainly due to a selective defect of CMI to Candida antigens. Twenty nine women suffering of NBRC, and in whom previous treatment with antibiotics and non-steroid anti-inflammatory drugs was unsuccessful, underwent oral transfer factor (TF) therapy. TF specific to Candida and/or to HSV was administered bi-weekly for the first 2 weeks, and then once a week for the following 6 months. No side effects were observed during treatment. The total observation period of our cohort was 24379 days with 353 episodes of cystitis recorded and a cumulative relapse index (RI) of 43. The observation period during and after treatment was 13920 days with 108 relapses and a cumulative RI of 23 (P < 0.0001). It, thus, seems that specific TF may be capable of controlling NBRC and alleviate the symptoms.

In vitro studies during long-term oral administration of specific transfer factor.

153 patients suffering from recurrent pathologies, i.e. viral infections (keratitis, keratouveitis, genital and labial herpes) uveitis, cystitis, and candidiasis were treated with in vitro produced transfer factor (TF) specific for HSV-1/2, CMV and Candida albicans. The cell-mediated immunity of seropositive patients to HSV-1/2 and/or CMV viruses was assessed using the leucocyte migration inhibition test (LMT) and lymphocyte stimulation test (LST) in presence of the corresponding antigens, and the frequency of positive tests before, during and after TF administration was studied. The data were stratified per type of test, antigen and the recipients' pathology, and statistically evaluated. For the LMT, a total of 960 tests were carried out for each antigen dilution, 3 different antigen dilutions were used per test. 240/960 tests (25.4%) were found positive during non-treatment or treatment with unspecific TF, whereas 147/346 tests (42.5%) were found positive when the antigen corresponding to the specificity of the TF administered to the patient was used (P < 0.001). When the data were stratified following pathology, a significant increased incidence of positive tests during specific treatment was also observed (0.0001 < P < 0.05). In the LST (1174 tests), a significant increase of thymidine uptake was observed in the absence of antigen (control cultures), during treatment with both specific and unspecific TF, but also in the presence of antigen and/or autologous serum during specific TF administration (P < 0.0001). TF administration also significantly increased the soluble HLA class I antigens level in 40 patients studied to this effect.

In situ echoguided extracorporeal shock wave lithotripsy of ureteric stones with the Dornier MPL 9000: a multicentric study group.

OBJECTIVE: To study the efficacy of the Dornier MPL 9000 lithotripter with a real time ultrasound transducer in the localization and treatment of upper and prevesical ureteric stones. PATIENTS AND METHODS: Two-hundred and eighty-five patients with pre-vesical ureteric stones and 247 patients with upper ureteric stones underwent extracorporeal shock wave lithotripsy (ESWL) using ultrasound targeting, under no regional or general anaesthesia. RESULTS: At follow-up after 3 months 97% of patients with pre-vesical stones and 96% with upper ureteric stones were stone free. Ninety-nine patients were treated more than once. The average number of sessions of ESWL for all patients was 1.19 (1.17 for patients with prevesical stones and 1.22 for those with upper ureteric stones). Ureteric stenting was employed in 6% of cases. The infrequent use of ureteric stenting did not reduce ESWL efficacy, nor increase either the complication or the retreatment rates. In many cases upper urinary tract dilatation was provoked by administering intravenous fluid and a diuretic. CONCLUSION: In situ echoguided ESWL is a simple, safe and effective technique for treating ureteric stones which can be detected on ultrasound.

Phase I-II pilot study on the efficacy and tolerability of neoadjuvant chemotherapy (Rescue M-VEC) and preoperative radiation therapy for infiltrating bladder cancer: results of an 18-month follow-up.

In spite of the improvement of surgical techniques used alone or in combination with preoperative radiation therapy, more than 50% of the patients with infiltrating transitional cell carcinoma (TCC) of the bladder die of distant metastases. Systemic antiblastic polychemotherapy has been reported to achieve a complete remission rate of approximately 30% in patients with infiltrating bladder TCC, although there are still doubts relative to the duration of such complete remissions. This study investigated the efficacy and tolerability of a preoperative chemo- and radiotherapeutic treatment modality and the possibility of performing preservative surgery. Thirty-seven patients with bladder TCC stage T2-T4, N0, M0, have been subjected to neoadjuvant chemotherapy according to the "Rescue M-VEC" scheme of methotrexate 30 mg/m2 +folinic acid 15 mg. after 24 hours on days 1, 15, 22; vinblastine 3 mg/m2 on days 1, 15, 22; epidoxorubicin 30 mg/m2 on day 1 and cisplatin 70 mg/m2 on day 1. The course was repeated from day 29. After 2 "Rescue M-VEC" courses, the patients received pelvic cobalt tele-therapy (CTT) combined with cisplatin 24 mg/m2/week. The patients were then restaged. Those with complete remission (CR) received consolidation radiotherapeutic boost combined with cisplatin 24 mg/m2/week, avoiding radical cystectomy. Such treatment was also given to patients with significant partial remission (PR) who had undergone TUR or partial cystectomy. In all the remaining cases we carried out radical cystectomy. We obtained 45.7% CR, 31.4% PR and 22.8% were non-responders (NR), of 35 patients who were evaluable at restaging. Only 9 radical cystectomies were performed in this series. The overall survival rate was 80.6% at a mean follow-up of 18.1 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Irrepressible renal colic from spontaneous subcapsular hematoma as a sign of presentation of renal neoplasia. Case report and review of the literature.

Renal adenocarcinoma can present with a wide range of symptoms and clinical signs and among them pain is the more frequent. As a matter of fact, it can also assume the features of a reno-ureteral colic. This kind of symptom, however, is more frequently combined with macro-hematuria and seldom presents alone, even in the initial phases of the clinical course. In this case, and if it assumes the features of strong and irrepressible pain, it can probably be related to sudden and remarkable hematic harvest in subcapsular space or, owing to its breach, in perirenal space. Besides the benign neoplastic pathology (angiomyolipoma) or the malignant one, the spontaneous subcapsular or perirenal hematoma may be due to several other etiopathogenetic factors, the most significant being arteriopathy (poliarteritis, aneurysms), phlogosis and hemocoagulopathy. The present case has prompted the authors to underscore the importance and the meaning of isolated algetic lumbar symptomatology in the diagnosis of complicated renal neoplasia. After a critical review of the literature on the modes of presentation of algetic symptomatology in renal adenocarcinoma, particularly spontaneous subcapsular hematoma, the authors report on a 53 year-old male patient who consulted because of a sudden irrepressible pain in his left flank, which could be only partially mitigated by stronger analgetics. Examinations urgently carried out (abdominal ultrasound, urography, pelviabdominal computed tomography) made it possible to diagnose a widespread secondary spontaneous subcapsular hematoma with left-sided solid renal neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Urethral stenosis: presuppositions on the physiopathology and our experience with internal urethrotomy]. / Stenosi uretrali: presupposti di fisiopatologia e nostra esperienza in tema di uretrotomia interna.

From 1982 till 1986 in our department 92 patients with single or multiple urethral strictures underwent internal urethrotomy according to Sachse. The Authors present a critical evaluation of etiology, pathophysiology, clinical-prognostic factors and therapeutic methodology. The results confirm the efficacy of internal urethrotomy in both the primary and relapsing urethral strictures.