Adaptation and validation of an Italian version of the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI).

OBJECTIVE: The Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) is a measure of health-related quality of life (HRQoL) in advanced hormone-resistant prostate cancer. In this study, we aimed at performing a cross-cultural adaptation and validation of the Italian version of the PROSQOLI. PATIENTS AND METHODS: The original version of the PROSQOLI underwent several turnarounds of translations. A total of 472 patients treated with radical prostatectomy, radiotherapy or medical therapy were enrolled for the validation of the questionnaire. The PROSQOLI was administered together with the SF-12. Reliability indexes were calculated by using Cronbach alpha. To evaluate the validity of the construct, relationships between PROSQOLI and SF12 were assessed. The ANOVA test was used to evaluate the differences between groups of patients who had received different treatments. RESULTS: The reliability coefficient was 0.91. Item-to-total correlation indices were in most cases >0.70. The correlation between the scores of the PROSQOLI and those of the SF-12 questionnaire was high (r=0.8139, p<0.0001). The ANOVA test showed significant differences between groups (p<0.01) based on age, recurrence risk and treatment. CONCLUSIONS: The adaptation process showed that the PROSQOLI Italian version has high reliability and presents both convergent and discriminant validity. This version of the tool can be used to assess HRQoL in Italian men who underwent radical treatment for advanced prostate cancer.

Temperature monitoring during radiofrequency ablation of liver: in vivo trials.

Radiofrequency ablation (RFA) is a minimally invasive procedure used to treat tumors by means of hyperthermia, mostly through percutaneous approach. The tissue temperature plays a pivotal role in the achievement of the target volume heating, while sparing the surrounding healthy tissue from thermal damage. Several techniques for thermometry during RFA are investigated, most of them based on the use of single-point measurement system (e.g., thermocouples). The measurement of temperature map is crucial for the real-time control and fine adjustment of the treatment settings, to optimize the shape and size of the ablated volume. The recent interest about fiber optic sensors and, among them, fiber Bragg gratings (FBGs) for the monitoring of thermal effects motivated further investigation. In particular, the feature of FBGs to form an array of several elements, thus to be inscribed within the same fiber, allows the use of a single probe for the multi-points monitoring of the tissue temperature during RFA. Hence, the aim of this study is the development and characterization of a needle-like probe embedding an array of three FBGs, which was tested on pig liver during in vivo trials. The needle allows a safe and easy insertion of the fiber optic within the liver. It was inserted by ultrasound guidance into the liver, and monitored the change of tissue temperature during RFA controlled by the roll-off technique. Also the measurement error induced by breathing movements of the liver was assessed (less than 3 °C). Results encourage the use of the probe in clinical settings, as well as the improvement of some features, e.g., a higher number of FBGs for performing quasi-distributed measurement.

Monitoring of thermal treatment by linearly chirped fiber Bragg grating sensors: feasibility assessment during laser ablation on ex vivo liver.

In this work a spatially-resolved fiber optic temperature sensor has been characterized in a wide range of gradient applied on its active area (from -35 °C to +35 °C). Preliminary experiments to assess its feasibility for application in laser ablation have been performed. The sensor under test is a linearly chirped fiber Bragg grating (FBG), with 1.5 cm-length of active area. It can be considered as a chain of several FBGs, each able to sense local temperature. The sensor response to the gradient has been analyzed in terms of its spectrum width (full width at half maximum). There is a linear relationship between the full width at half maximum and the gradient, with a sensitivity of 0.0087 nm°C-1. The feasibility test using the linearly chirped FBG during laser ablation showed promising results: it is able to detect both the thermal gradients along is active area and the average temperature increment during the procedure.

Pathology of BPH.

Much research has been conducted to determine which tissue (epithelium or stroma) in the prostate gives rise to benign prostatic hyperplasia (BPH). Considering that BPH displays two structural compartments, stromal and epithelial and that the periurethral and transitional regions are particularly involved, the immunohistochemical and regional evaluation of steroid receptors concentration, 5 alpha reductase, DHT and estrogen activity, may show important data on the role of these factors in BPH development. We started a immunohistochemical study on the epidermal growth factor (EGF) concentrations in the periurethral, central and pericapsular zones of BPH samples, considering the stroma-epithelium ratio; investigations are performed on BPH patients submitted to transvesical prostatectomy. Considering that the periurethral zone is particularly involved in BPH, the presence of high concentration of growth factors in this region, may support the concept of their involvement in BPH.

Plant extracts in BPH.

In Italy plant extracts represent 8.6% of all pharmacological prescriptions for Benign Prostatic Hyperplasia (data from 1991). This review evaluates all the suggested mechanisms of action for plant extracts. Recently we demonstrated an antiestrogenic effect of Serenoa Repens in BPH patients. Clinical trials with plant extracts have yielded conflicting results. In a recent review by Dreikorn and Richter, only five placebo controlled studies were found. Moreover, as opposed to chemically defined drugs, it is possible that for these extracts the active ingredients are not known; consequently pharmacodynamic and pharmacokinetic data are often missing. The International Consultation of Benign Prostatic Hyperplasia (Paris, June 1991) concluded that, to date, phytotherapeutic agents must be considered as a symptomatic treatment. Now more adequate pharmacological and clinical studies, placebo controlled, should determine the exact role of these drugs in the treatment of BPH.

Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients.

A double-blind placebo-controlled study was performed in 35 benign prostatic hypertrophy (BPH) patients never treated before. The patients were randomized into two groups, the 1st (18 cases) receiving Serenoa repens extract (160 mg t.d.) for 3 months up to the day before the operation of transvesical adenomectomy and the 2nd (17 cases) receiving placebo. Steroid receptors were evaluated in the nuclear (n) and cytosolic (c) fraction using the saturation analysis technique (Scatchard analysis or single saturating-dose assay) for androgen (AR) and estrogen (ER) receptors and the enzyme immunoassay (EIA) for ER and progesterone receptors (PgR). Scatchard analysis of ERc and ERn revealed the presence of two classes of binding sites, one with high-affinity low-capacity binding and the other with low-affinity high-capacity binding. In the untreated BPH group, ER were higher in the n than in the c fraction: ERn were positive in 14 cases and ERc in 12 of 17 cases. In the BPH group treated with S. repens extract on the contrary, ERn were negative for both binding classes in 17 cases and ERc in 6 of 18 cases. Using EIA, ERn and ERc were detected in all 15 samples examined, but in the treated group, ERn were significantly (p less than 0.01) lower than in the untreated group, whilst ERc remained almost unchanged. Similar results were obtained measuring PgR: the n fraction of the treated group prostatic samples was significantly (p less than 0.01) lower than that of the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological and clinical implication of cellular DNA content in renal cell carcinomas.

DNA flow cytometric analysis (FCM) was performed on surgical bioptic samples taken from 82 renal cell carcinomas. FCM has evidenced that 35% (29/82) of renal carcinomas resulted diploid, 65% (53/82) aneuploid and of the latter 22% (12/53) multiclonal. Our results do not indicate any relationship among cytometric ploidy, Fuhrman grading, Robson and pTNM staging. A possible interesting increase of aneuploidy frequency was observed between the NMV (66%) subgroup and the no zero NMV (90%) subgroup, while in diploid patients these values were 40% and 10%, respectively. Follow-up data evidence a significant difference in survival pattern of patients between diploid and aneuploid groups. In conclusion, our results show that cytometric ploidy is a potential important prognostic parameter in survival term.

The prognostic value of DNA content in patients with prostatic carcinoma.

In 80 patients with pathologically proven prostatic cancer, DNA content was correlated to grade, stage and survival. The survival curve and duration of response to therapy in these patients was examined. At the end of follow-up the cumulative survival curve in the aneuploid patients was 0.40, according to the Kaplan-Meier method, while in the diploid population it was 0.65. Differences between the two groups, aneuploid and diploid, were observed within the various histological subgroups: survival in the G2 population was 0.57 for the diploid and 0.30 for the aneuploid whereas in the G3 patients it was respectively 0.69 for the diploid and 0.05 for the aneuploid patients.

New ultrasensitive assay development by using monoclonal antibodies for detecting prostate-specific antigen.

The Serono Maia Clone prostatic-specific antigen (PSA) kit incorporates an immunoradiometric assay for the measurement of PSA in the serum. The method can be used over a range of 0-100 ng/ml without dilution. Standard concentrations are 0, 0.4, 1, 5, 20, and 100 ng/ml. Up to date, 373 normal men, 89 normal women, 117 prostatic carcinoma, 98 other carcinoma, and 85 benign prostatic hypertrophy have been tested. The aim of this study is to evaluate the sensitivity and specificity of a new immunoassay method for the determination of PSA, that could be able to evaluate low levels of PSA, resulted undetectable with other methods. This ability could be useful in patients treated with hormone-suppressive therapy or after radical prostatectomy. We have collected all low values present in samples examined. With the Serono Maia Clone PSA kit only 26.7% of these have been evaluated as 'out' values as opposed to 46.5% with the Hybritech kit.

Phase I study of vincristine and escalating doses of etoposide.

A phase I trial of vincristine and etoposide was designed following the identification of a potentially synergistic antitumor effect in a murine model. The dose of vincristine was fixed (0.5 mg daily for 3 days). Etoposide was given at 1 of 3 total dose levels (250, 500, or 750 mg/m2) per treatment. Each dose was given in 3 equal fractions and each fraction was given daily for 3 days, i.e., 83.3 mg/m2/d x 3d, 166.7 mg/m2/d x 3d, or 250 mg/m2/d x 3d. A total of 31 patients were entered into study including 10, 18, and 3 patients treated at the 250, 500, and 750 mg/m2 dose levels, respectively. Dose-limiting toxicity occurred at the 750 mg/m2 level, in which Grade 4 myelosuppression developed in all of the patients. Life-threatening gram negative sepsis occurred in two of these patients and both required platelet transfusions. Grade 3-4 WBC toxicity was observed in 9 of 16 (56%) evaluable patients treated at the 500 mg/m2 level, but reversal of toxicity was generally rapid with repeat courses given at 3 week intervals in most patients. Non-hematologic toxicity was negligible. Objective responses were observed in 2 of 4 patients with Hodgkin's disease. The starting dose of etoposide recommended for phase II trials of this agent in combination with vincristine is 500 mg/m2; dose escalation may be possible in some patients.

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies.

Cytosine arabinoside (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m2 as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9-12 and 21-24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m2 X 2 doses of ara-C and 50 mg/m2 of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.

Vinblastine infusion in non-Hodgkin's lymphomas: lack of total cross-resistance with vincristine.

Historically, vinblastine given by intravenous bolus injection has not been an effective treatment for non-Hodgkin's lymphomas; vincristine has displayed greater activity. Also, vinblastine has generally been considered to be cross-resistant with vincristine in such patients. In an attempt to overcome these obstacles, a protracted infusion of vinblastine was administered (0.5-1.5 mg/m2 per day for 5 days) and repeated every 3 weeks. Partial responses were observed in 4 of 29 (14%) patients with a variety of non-Hodgkin's lymphoma lasting 2.4, 2.4, 5.5, and 9.0 months. Just prior to treatment the responding patients had received and eventually become refractory to vincristine. These data show a lack of total cross-resistance between vinblastine and vincristine which might have important therapeutic implications in this disease.

Recombinant gamma interferon in advanced breast cancer: a phase II trial.

Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance status of 0-2 (Karnofsky greater than or equal to 50). Thirteen patients had two or three sites of metastatic disease and seven were estrogen receptor positive. No complete or partial responses were noted. Although some patients had brief periods of stable disease, almost all patients progressed after one or two courses. Only one patient was able to receive six courses of induction therapy and a brief course of maintenance. Flu-like symptoms and nausea were seen in all patients; vomiting and anorexia were frequent. Hepatic toxicity manifested by enzyme elevation was common and was most severe in patients with liver metastases. In this study a highly purified biologically active gamma interferon was not associated with anti-tumor activity in previously treated women with metastatic breast cancer.

A phase I trial of recombinant leukocyte alpha 2 interferon in patients with advanced malignancy.

Seventeen patients with advanced, previously treated malignancies were entered into a phase I trial utilizing recombinant DNA produced alpha 2 leukocyte interferon (rIFN-alpha 2). Sixteen patients were evaluable. Patients were to receive rIFN-alpha 2 by either the I.V. or I.M. route for 35 consecutive days. The dosage was identical by both routes, and patients were escalated from 3 X 10(6) to 10 X 10(6) to 30 X 10(6) to 50 X 10(6) and to 100 X 10(6) I.U. every 7 days. No patient was able to tolerate the consecutive treatment protocol as planned. Dose-limiting toxicity was a flu-like syndrome in 10 patients and was usually associated with a fall in performance status. Confusion resulted in study withdrawal for five patients, four receiving rIFN-alpha 2 by the I.M. route. Hematologic and liver function abnormalities were common, usually transient, and not associated with clinical sequelae. One patient with non-Hodgkin's lymphoma showed substantial improvement; otherwise, all had stable or progressive disease. Pharmacologic studies indicated substantial serum levels at doses greater than or equal to 10 X 10(6) I.U. regardless of route. No consistent changes in NK activity, lymphocyte subpopulations, or immunoglobulin levels were noted, and no patient developed antibodies to rIFN-alpha 2. The dose and schedule used here indicate that high levels of serum rIFN-alpha 2 activity are obtainable by either the I.M. or I.V. route. Intermittent rather than daily dosage is more likely to be better tolerated and should be considered for phase II trials.