Efficacy and safety of fibrin sealant patch in the treatment of air leakage in thoracic surgery.

AIM: Air leakage represents a major problem in lung surgery. Absorbable fibrin sealant patch (AFSP), a collagen sponge coated with human fibrinogen and thrombin, can be used as an adjunct to primary stapling or suturing. This study compared the efficacy of AFSP with manual suturing after primary stapling. METHODS: This was a prospective, multicenter, randomized study. Patients undergoing lobectomy, bilobectomy, anatomical segmentectomy for lung cancer or wedge resection for pulmonary metastasis with air leakage grade 1 or 2 according to Macchiarini scale after stapler suture were randomized to receive AFSP or standard surgical treatment (ST). The primary endpoint was the reduction of intraoperative air leakage intensity. Duration of postoperative air leakage and number of days until removal of last chest drain were secondary endpoints. Safety was recorded for all patients. RESULTS: A total of 346 patients were enrolled in 14 centres, 179 of whom received AFSP and 167 ST. Intraoperative air leak intensity was reduced in 90.5% of AFSP patients and 82% of ST patients (P=0.03). A significant reduction in postoperative air leakage duration was observed in the AFSP group (P=0.0437). The median number of days until removal of last drainage was 6 (3-37) in the AFSP group and 7 (2-27) in the ST (P=0.38). Occurrence of adverse events was comparable in both groups. CONCLUSION: AFSP was more efficacious than standard ST as an adjunct to primary stapling in reducing intraoperative air leakage intensity and duration of postoperative air leakage in patients undergoing pulmonary surgery. AFSP was well tolerated.

Phase I/II study of gemcitabine plus vinorelbine as first-line chemotherapy of non-small-cell lung cancer.

PURPOSE: To determine the maximum-tolerated dose of gemcitabine when combined with a fixed dose of vinorelbine in the treatment of non-small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the activity of this combination. PATIENTS AND METHODS: Sixty-eight patients with stage IIIB/IV NSCLC were treated with vinorelbine at fixed dose of 30 mg/m(2) intravenously and gemcitabine at increasing dose levels from 800 to 1,500 mg/m(2) intravenously on days 1 and 8 every 3 weeks. RESULTS: In phase I, dose-limiting toxicity occurred at the dosage of 1,500 mg/m(2) gemcitabine, with three of five patients developing grade 4 thrombocytopenia. In phase II, with gemcitabine at 1,200 mg/m(2), 19 (36%) of 52 assessable patients responded. Objective response was observed in 11 (39%) of 28 patients with stage IIIB disease and in eight (33%) of 24 patients with stage IV. The median time to progression was 29 weeks (range, 2 to 41 weeks; 35 weeks and 16 weeks for stages IIIB and IV, respectively), and median survival was 54 weeks (range, 2 to 84+ weeks; 63 weeks and 42 weeks for stages IIIB and IV, respectively). One-year survival was 64% for patients with stage IIIB disease and 29% for those with stage IV. Clinical benefit response was observed in 29 (59%) of 49 assessable patients. Grade 4 leukopenia and thrombocytopenia were uncommon (6% and 8% of cases, respectively); however, grade 3/4 leukothrombocytopenia occurred more frequently in patients aged more than 70 years (52% and 24%, respectively). CONCLUSION: The combination of vinorelbine and gemcitabine is effective and tolerable in the treatment of NSCLC, thus deserving randomized trials with cisplatin combination regimens.

Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group.

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non-small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of < or = 70 years, and an Eastern Cooperative Oncology Group performance status < or = 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m(2), gemcitabine 1,000 mg/m(2), and vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m(2) on days 1 and 29 and vinorelbine 30 mg/m(2)/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P <.01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group.

PURPOSE: In a previous phase I study cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR) combination therapy was safe and very active in patients with non-small-cell lung cancer (NSCLC). This study was aimed at better defining the activity and toxicity of this regimen. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients, age < or = 70 years, with stage IIIB or IV NSCLC and a performance status of 0 or 1 (Eastern Cooperative Oncology Group scale) were randomized to two treatment arms. Patients on arm A received CDDP 50 mg/m2, GEM 1,000 mg/m2, and VNR 25 mg/m2 on days 1 and 8 of an every-3-weeks cycle (57 patients). Patients on arm B received CDDP 80 mg/m2, epirubicin 80 mg/m2, and vindesine 3 mg/m2, all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients). In December 1996, randomization was stopped early, and an additional 30 patients were treated with the experimental regimen to obtain a more accurate estimation of its activity rate. RESULTS: Among 87 patients who received the CDDP-GEM-VNR combination, four complete responses (CRs) and 46 partial responses (PRs) were observed, for an overall response rate of 57% (95% confidence interval [CI], 46% to 68%). Two CRs and 18 PRs were recorded among 54 patients on arm B, giving a 37% activity rate (95% CI , 24% to 51%). After a median follow-up duration of 19 months, the median progression-free and overall survival durations were 32 and 50 weeks in arm A, and 18 and 33 weeks in arm B, respectively. World Health Organization grade 3 to 4 neutropenia and thrombocytopenia occurred in 46% and 14% of patients in arm A and in 22% and 11% of those in arm B, respectively. Severe nonhematologic toxicity was uncommon in both arms. CONCLUSION: The CDDP-GEM-VNR combination is a highly effective treatment for patients with advanced NSCLC and has a manageable toxicity. A phase III trial comparing this new combination with both CDDP-VNR and CDDP-GEM regimens is underway.

The Na(+)-Ca++ exchanger in central nerve endings: the relationship between its pharmacological blockade and dopamine release from tuberoinfundibular hypothalamic neurons.

2', 4'-Dimethylbenzamiloride (DMB), an inhibitor of Na(+)-Ca++ antiporter dose-dependently (10-100 microM) inhibited Na(+)-dependent 45Ca++ efflux from brain synaptosomes. This compound was also able to stimulate basal release of [3H]DA from superfused TIDA neurons. Another amiloride analogue, 5-N-methyl-N-guanidinocarbonylmethylamiloride (MGCMA, 100-300 microM), which lacks of inhibitory properties on the Na(+)-Ca++ antiporter, failed to modify basal [3H]DA release from TIDA neurons. In addition, when the antiporter operates as a Ca(++)-influx pathway, DMB dose-dependently inhibited Na(+)-dependent 45Ca++ uptake in brain synaptosomes, whereas it did not prevent K(+)-induced 45Ca++ uptake, which reflets the activation of voltage-operated Ca++ channels. Finally DMB inhibited ouabain-induced [3H]DA release, which depends on the activation of the Na(+)-Ca++ exchanger due to the inhibition of the Na+/K(+)-ATPase pump.

[Immunosuppressive action and effects of amethopterin on the lymphoid tissue of the rabbit appendix]. / Azione immunosoppressiva ed effetti dell'ametopterina sul tessuto linfoide dell'appendice nel coniglio.

Effects of amethopterin (MTX) on lymphoid tissue of rabbit appendix have been evaluated. The drug caused an evident depletion of lymphoid cells. This finding suggested the relevance of cytotoxicity in the mechanism of immune suppression. Discontinuation of drug treatment demonstrated a tendency toward the reorganization of the lymphoid tissue.

[Immunologic and cytologic aspects of Hashimoto's thyroiditis during therapy with thymopentin]. / Aspetti immunologici e citologici della tiroidite di Hashimoto in corso di terapia con timopentina.

Hashimoto's thyroiditis is an autoimmune disease characterized by the presence of thyroid autoantibodies and frequent coexistence of other autoimmune disorders. The object of our research was to examine the peripheral blood and fine-needle cytology modifications in patients with this disease during therapy with Timopentina. Our results suggested a possible therapeutic effect of Timopentina, as an alternative to traditional cortisone treatment.

[Surgery of lung metastasis--indications, results and prognostic factors as an interdisciplinary concept]. / Metastasenchirurgie der Lunge--Indikation, Ergebnisse und prognostische Faktoren im interdisziplinären Konzept.

Surgical therapy of lung metastases nowadays is an established procedure. The operation's purpose is the radical and therefore potential curative resection. Beside there are diagnostic and palliative indications. Beside there are diagnostic and palliative indications. Median sternotomy is the standard approach for revision of both lungs even in unilateral seeming disease. Preoperative staging is not reliable concerning number and extension of metastases. From 1972 to 1991 843 operations for lung metastases were carried out in 729 patients in the surgical department of the "Thoraxklinik Heidelberg-Rohrbach". 30-day-mortality amounted to 2.9%, 5-year-survival-rate was 33% overall from date of metastases resection. The best results were achieved in testicular cancer with 67% 5-years-survival-rate, poorest survival was observed in melanomas with 12% 3-years-survival. Beside the primary tumor and partly dependent on it several prognostic factors were relevant: radicality, sarcoma vs carcinoma in favour of carcinomas, disease-free interval, type of resection, thoracic lymphnode involvement. As figured out by multivariate analysis the prognostic influence of the factors varies considerably due to the kind of primary tumor. Surgery of lung metastases is part of an interdisciplinary oncological therapeutical concept and offers a prolonged survival to most of the patients and the possibility of cure to some. Even if prolongation of life is not feasible an improved quality and therefore a good palliation is obtained.