povidone-iodine and Mesothelioma

Topics: Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Pneumonectomy; Povidone-Iodine; Therapeutic Irrigation

We evaluated the long-term results of pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, prophylactic chest wall radiotherapy (21 Gy), and systemic chemotherapy in patients with malignant pleural mesothelioma.. A cohort of patients having surgery between January 2004 and December 2013 were retrospectively studied. All patients received prophylactic radiotherapy postoperatively and all were supposed to receive systemic chemotherapy, either preoperatively or as adjuvant therapy. Patients were reviewed at 30 days, then followed up 6-monthly. (18)F-FDG-PET-CT was used routinely to diagnose disease recurrence. Second-line therapies were administered when appropriate. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox regression analysis.. One hundred two patients had P/D followed by prophylactic radiotherapy and were referred for adjuvant chemotherapy. Median age at operation was 64 years. Eighty-one patients (79.4%) were male; 57 patients (55.9%) had complete macroscopic resection. Thirty-day mortality was nil and 30 patients (29.4%) experienced postoperative complications. Seventy-three patients had epithelioid mesothelioma (71.5%). Sixty-eight patients (66.6%) had N0 disease. Ninety-six patients (94.1%) received the planned 4 to 6 chemotherapy cycles. At last follow-up, 49 patients were alive. Univariate analysis showed no significant difference when sex, age >70 years, nodal status, or prior chemotherapy were considered. The overall median survival was 32 months and 5-year survival rate was 23.1%. Median survival and 5-year survival rates were 35.0 months and 30.7% for epithelioid mesothelioma and 15 months and 7% for nonepithelioid mesothelioma, respectively (P = .0001). Median survival was 45.0 months for R0-R1 resection versus 17.4 months for R2 resection (P = .0001).. P/D, hyperthermic pleural lavage with povidone-iodine, prophylactic chest wall radiotherapy, and systemic chemotherapy is a safe and well-tolerated multimodality therapy.

Topics: Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Multimodal Imaging; Neoplasm Recurrence, Local; Pleural Neoplasms; Pneumonectomy; Positron-Emission Tomography; Povidone-Iodine; Prognosis; Retrospective Studies; Survival Rate; Therapeutic Irrigation; Tomography, X-Ray Computed; Treatment Outcome

Topics: Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Male; Mesothelioma; Pleural Neoplasms; Pneumonectomy; Povidone-Iodine; Therapeutic Irrigation

Povidone-iodine (PVP-I) or Betadine, owing to its antineoplastic activity, is also used as an adjuvant during intra-abdominal or intrathoracic surgery. However, the protocol of PVP-I administration has not been optimized to achieve the best antitumoural efficacy. We aimed to determine the optimal concentration of PVP-I, the time of incubation and the mechanism of cell death by analysing the effect of different doses and time of administration of PVP-I on the cell viability of different mesothelioma cell lines.. Four different cell lines (MET 5A/normal mesothelium; H2052/sarcomatoid mesothelioma; ISTMES2/epithelial mesothelioma; MSTO/biphasic mesothelioma) were incubated with increasing concentrations of diluted PVP-I (0.0001; 0.001; 0.01; 0.1; 1%) for 5, 10, 30, 60 min and 24 h, respectively. Cell viability was determined using cell direct cytotoxicity assay and cell death was determined through flow cytometry assay analysis. The superoxide dismutase activity was assessed functionally through a specific inhibitor to evaluate the mechanism of cell death.. The antiproliferative effect of PVP-I varied largely among different cell lines in a dose- and time-dependent manner. At 0.1% concentration for 10 min of incubation, the percentage of viable cells was 0.5 ± 0.1; 0.8 ± 0.5 and 0% (P < 0.01) for MET5A, ISTMES2 and MSTO, respectively. Conversely, the same concentration did not significantly affect the H2052 cell line which was completely suppressed at a 1% concentration of PVP-I. Double staining of Annexin V and DNA showed that PVP-I induced cell death in all four cell lines via necrosis depending on PVP-I concentration. However, H2052 was found to be more resistant than MSTO, ISTMES2 and MET 5A cells lines. The activity of superoxide dismutase was significantly inhibited in all cell lines.. Our results confirmed the anti-neoplastic activity of PVP-I especially on ISTMES2 and MSTO cell lines. With respect to chemotherapy pleural irrigation, washing with PVP-I is cost-effective and easy. If confirmed by larger studies, our findings suggest that the intrapleural irrigation with PVP-I (0.1% concentration for 10 min) in patients with epithelial or biphasic mesothelioma undergoing cytoreductive surgery might be applied in thoracic surgery practice to prevent neoplastic cell growth.

Topics: Antineoplastic Agents; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Povidone-Iodine; Superoxide Dismutase

Malignant pleural mesothelioma is a fatal neoplasm related to asbestos exposure. We investigated the effects of pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy in patients with malignant pleural mesothelioma.. Observational prospective study of patients referred for multimodality therapy and operated on at our institution between October 2004 and May 2010. Thirty-six selected patients underwent P/D and hyperthermic pleural lavage, prophylactic radiotherapy, and adjuvant chemotherapy. All patients were reviewed at 4 weeks and then 6 monthly in the outpatient clinic, with positron-emission tomography-computed tomography. Second-line treatments were administered when appropriate.. Thirty-day mortality was nil. Nine patients experienced postoperative complications: persistent air leak (n = 5, 13.9%), chylothorax requiring surgical intervention (n = 4, 11%), and adult respiratory distress syndrome (n = 1, 3.9%). Fourteen of 36 patients were alive at last follow-up (median follow-up: 33 months, range: 12-63 months). Ten patients were alive with no evidence of disease recurrence, four patients were alive with disease recurrence, and 22 patients had died of disease progression. Overall median survival (Kaplan-Meier) was 24 months (95% confidence interval: 18.5-29.4 months). One-year survival was 91.7%, and 2-year survival was 61%. Patients undergoing complete macroscopical resection (R0-R1) had a significantly better survival than those undergoing an incomplete macroscopical resection (R2) (median overall survival: 32 months versus 18.9 months, p = 0.012).. In our experience, P/D combined with hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy is a well-tolerated multimodality treatment associated with low morbidity and mortality. This multimodality treatment compares favorably with classical trimodality regimens involving chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy, in our experience. Study limitations include small sample size, nonrandomization, and patient selection bias.

Topics: Aged; Anti-Infective Agents, Local; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Mesothelioma; Middle Aged; Neoplasm Staging; Pleural Neoplasms; Pneumonectomy; Positron-Emission Tomography; Povidone-Iodine; Prospective Studies; Radiotherapy, Adjuvant; Survival Rate; Treatment Outcome

Topics: Animals; Biomedical Research; Bleomycin; Breast Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Mesothelioma; Pleural Effusion, Malignant; Pleurodesis; Povidone-Iodine; Rabbits; Talc; Tetracycline

Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies.. Fifty microlitre containing 1 x 10(6) cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4 ml of cisplatin-solution (100mg(2)/kg BW), cisplatin combined with the fibrin-based sealant Vivostat, 4 ml taurolidine 2%, repeated injection of 1 microg of the chemokine CCL-19 at the tumour site and 4 ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4 ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence.. Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (+/-0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat with significant decrease of the longest, widest and thickest diameter of the recurrence.. With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat significantly reduced the extent of local recurrence.

Topics: Animals; Anti-Infective Agents, Local; Antineoplastic Agents; Cell Line, Tumor; Chemokine CCL19; Chemokines, CC; Cisplatin; Combined Modality Therapy; Disease Models, Animal; Fibrin Tissue Adhesive; Male; Mesothelioma; Neoplasm Recurrence, Local; Pleural Neoplasms; Pneumonectomy; Povidone-Iodine; Rats; Rats, Inbred F344; Taurine; Thiadiazines

Taurolidine and povidone-iodine (PVP-I) are used in every day clinical practice, taurolidine as a broad spectrum antibiotic, and PVP-I as an antiseptic. The type of cell death induced in malignant pleural mesothelioma (MPM) cell lines by these agents was compared, and their ability to sensitize to chemotherapy assessed. Both taurolidine and PVP-I inhibited MPM cell growth after 7.5min incubation, but taurolidine was more effective at later time points and was more specific towards tumour cells than PVP-I. Taurolidine induced death by caspase-dependent and independent mechanisms, whereas in contrast, PVP-I induced a necrotic phenotype that was not caspase-dependent. Interestingly, both taurolidine and PVP-I induced the production of reactive oxygen intermediates and decreased mitochondrial membrane permeability, and cell death was inhibited by the oxygen scavenger N-acetyl cysteine. Taurolidine but not PVP-I treatment resulted in p53 activation in 2/3 MPM cell lines and a decrease in the protein levels of survivin, Bcl-2 and Mcl-1. Survivin also decreased in response to PVP-I whereas Bcl-xL remained unaffected by both treatments. Targeting of Bcl-xL with siRNA sensitized MPM cells to taurolidine and taurolidine treatment sensitized MPM cells to cisplatin-induced apoptosis. In conclusion, taurolidine and PVP-I are both cytotoxic to human MPM cells at early and late time points and induce reactive oxygen intermediate production. Taurolidine induces apoptosis and necrosis, activates p53 and sensitizes cells to cisplatin, whereas PVP-I inhibits cell growth via necrosis. Both agents are promising candidates for use in local treatment within multimodality concepts for MPM.

Topics: Anti-Infective Agents, Local; Antineoplastic Agents; Biopsy; Blotting, Western; Caspase 3; Cell Death; Cell Line, Tumor; Cell Membrane Permeability; Cell Proliferation; Cell Survival; Cisplatin; Drug Therapy, Combination; Enzyme Activation; Flow Cytometry; Gene Expression Regulation, Neoplastic; Genes, p53; Humans; Mesothelioma; Mitochondrial Membranes; Pleural Neoplasms; Povidone-Iodine; Reactive Oxygen Species; Taurine; Thiadiazines