Effective treatment of malignant pleural effusion by minimal invasive thoracic surgery: thoracoscopic talc pleurodesis and pleuroperitoneal shunts in 101 patients.

BACKGROUND: For effective palliation of patients with malignant pleural effusion due to advanced neoplastic disease, any proposed treatment should have low procedure-related mortality and morbidity. METHODS: The clinical outcome of 119 thoracoscopies in 101 patients (56 women, 45 men), from 42 to 91 years of age (mean, 68 +/- 9 years) with malignant pleural effusions was evaluated in a retrospective study. Video-assisted thoracoscopy (VATS) talc pleurodesis was done in 105 instances, and a pleuroperitoneal shunt was performed 14 times as an alternative when complete expansion of the lung could not be achieved due to tumor implants on the visceral pleura. RESULTS: The VATS talc pleurodesis resulted in clinically significant improvement of dyspnea in 92.2% of the patients. Thirty-day mortality was 2.8% and morbidity was 2.8%. The mean duration of postoperative survival was 6.7 months. Recurrent pleural effusion occurred in 5.7% of patients after a mean interval of 6 months. Clinical relief of dyspnea was obtained in 73% of the patients treated with pleuroperitoneal shunts. Thirty-day mortality in this group was 21% and morbidity was 14.3%. The mean duration of survival was 4.2 months. CONCLUSIONS: The VATS talc pleurodesis is appropriate for palliation of patients with malignant pleural effusions and should be performed once the diagnosis has been confirmed. Patients with lungs trapped by visceral carcinomatosis may benefit from placement of a pleuroperitoneal shunt as an alternative.

Bypass surgery versus palliative pancreaticoduodenectomy in patients with advanced ductal adenocarcinoma of the pancreatic head, with an emphasis on quality of life analyses.

BACKGROUND: In some centers, palliative resection (PR; partial pancreaticoduodenectomy) is, in selected cases, promoted in preference to double loop bypass (DLB) surgery for advanced pancreatic cancer. This prospective study compares PR with DLB, placing particular focus on patients' quality of life (QoL). METHODS: From 01/1993 to 09/2004, 167 patients were analyzed in a prospective single center study of palliative surgical treatment of advanced ductal adenocarcinoma of the pancreatic head. Thirty-eight underwent PR and 129 underwent palliative DLB. Patients undergoing DLB were divided into: (1) locally advanced disease (LAD-subgroup; n = 61; 47%) and (2) metastasized disease (MD-subgroup; n = 68; 53%). QoL was assessed using the EORTC QLQ-C30 questionnaire supplemented by a pancreatic cancer specific module. QoL data were collected pre-operatively and for up to 12 months after surgery. RESULTS: Median survival was 7.0 months (95% CI 4.09; 9.91) in PR patients and 6.0 months (95% CI 5.39; 6.61) in patients who received DLB. Mortality and morbidity were, respectively, 7.8 and 58% for PR, and 2.6 and 42% for DLB. QoL decreased more after PR than after DLB. The DLB-group recovered quicker, reaching pre-operative QoL levels after 3 months, and were less impaired when discharged. The LAD-subgroup and the MD-subgroup presented with equal levels of QoL. CONCLUSIONS: QoL analysis revealed favorable QoL data after DLB. Additionally, the survival rates of the two groups did not differ significantly, but morbidity and mortality rates in the PR group were elevated. Therefore, the use of PR for advanced pancreatic cancer needs to be carefully evaluated.

Apoptosis by gemcitabine in non-small cell lung cancer cell line KNS62 is induced downstream of caspase 8 and is profoundly blocked by Bcl-xL over-expression.

BACKGROUND: This study assesses the chemotherapeutic drug gemcitabine in the human non-small cell lung cancer (NSCLC) cell line KNS62 in relation to the CD95-induced apoptotic pathway, and the role of the anti-apoptotic protein Bcl-xL in vitro and in vivo. MATERIALS AND METHODS: Apoptosis was determined by JAM assay and DAPI staining analysis. Activation of key apoptotic proteins, including caspases 3, 8 and 9 and BID, as well as cytochrome c release and mitochondrial transmembrane potential (MTP), were measured. The impact of the caspase inhibitor zVAD on gemcitabine-induced apoptosis was quantified. The in vitro results were verified in vivo in an orthotopic murine xenotransplantation model. RESULTS: Gemcitabine treatment, as well as stimulation of CD95, resulted in cleavage of effector caspase 3 as well as its substrate PARP and caspase 9, followed by DNA fragmentation. Cleavage of caspase 8 was demonstrated after CD95 activation but not after the application of gemcitabine. In KNS62-Bcl-xL clones, release of cytochrome c and loss of mitochondrial transmembrane potential were suppressed. Consequently, apoptosis after gemcitabine therapy, as well as CD95-induced apoptosis, were significantly inhibited. Caspase inhibitor zVAD only partly reversed gemcitabine-induced DNA fragmentation. In vivo, there was a significant reduction in tumour volume under gemcitabine therapy. Bcl-xL over-expressing tumours were completely resistant to gemcitabine therapy. CONCLUSIONS: In NSCLC cell line KNS62 gemcitabine activated the mitochondrial apoptotic pathway downstream of mitochondria without activation of initiator caspases. Bcl-xL over-expression induced significant resistance to gemcitabine. In vivo, the anti-apoptotic effect of Bcl-xL was more pronounced than in vitro. Gemcitabine also induced caspase-independent DNA fragmentation in KNS62 cells.

[Video-assisted thoracoscopy for effective palliation of malignant pleural effusion. Pleurodesis--pleuroperitoneal shunt]. / Die videoassistierte Thorakoskopie zur effektiven Palliation maligner Pleuraergüsse. Pleurodese--Pleuroperitonealer Shunt.

Dyspnea and reduced physical capability mean a significant reduction in quality of life of patients with advanced tumor disease. Video-assisted thoracoscopic talc poudrage or alternatively placement of pleuroperitoneal shunts were retrospectively evaluated as procedures for definitive palliation.

Chronic spontaneous pneumothorax decortication after 130 days.

The case of a 21-year-old male with neglected and protracted spontaneous pneumothorax is reported. Video-assisted thoracoscopy after 130 days showed the lung to be trapped solely by a thick pleurovisceral membrane, which required open surgical decortication. Chronic pneumothorax is a rare complication of spontaneous pneumothorax. This is the second report on a chronic pneumothorax solely due to a pleurovisceral membrane and the longest reported interval until decortication.

[Effective treatment of malignant pleural effusion: Thoracoscopic talcum pleurodesis and pleuro-peritoneal shunt]. / Die effektive Behandlung des malignen Pleuraergusses. Thorakoskopische Talkumpleurodese--pleuroperitonealer Shunt.

BASIC PROBLEM: Definitive palliation of malignant pleural effusion demands a therapeutic procedure that is efficient with a low risk of complication and death. This study was undertaken to evaluate the outcome of thoracoscopic talcum pleurodesis (TTP), with insertion of pleuro-peritoneal shunt (PPS) for permanent drainage, if indicated. PATIENTS AND METHODS: The results of treating malignant pleural effusions were analysed retrospectively in 36 patients (15 men, 21 women; mean age 65 [48-89] years) who had undergone 37 video-assisted TTP and 6 PPS. RESULTS: TTP achieved significant improvement of dyspnoea in 89% of patients and PPS succeeded in providing permanent internal drainage even in cases of adherent pleura. CONCLUSION: Video-assisted TTP is the method of choice in the palliative treatment of malignant pleural effusions in the still expanding lung. In case of an adherent nonexpanding lung PPS provides effective and permanent palliation.

Human endostatin inhibits growth of human non-small-cell lung cancer in a murine xenotransplant model.

Overall prognosis in human NSCLC remains poor. Antiangiogenic treatment has become a promising concept for the treatment of solid malignancies. Our purpose was to evaluate the efficacy of recombinant HSENDO for the treatment of human NSCLC in an orthotopic murine xenotransplantation model. The efficacy of HSENDO was tested in vitro in cell-proliferation, cell-migration and tube-formation assays. In vivo, the effect of HSENDO on tumor growth was tested in s.c. xenotransplanted human NSCLC and on intrapulmonary induced human NSCLC. In vitro, HSENDO inhibited both human and rodent endothelial cell proliferation in a time- and dose-dependent fashion. Endothelial cell migration was inhibited by 97%. Tube formation of murine endothelial cells was inhibited and preexisting tubes degenerated after HSENDO exposure. In vivo, HSENDO delayed growth of s.c. xenotransplanted tumors. Immunohistochemic staining demonstrated no change in microvessel density but a significant reduction of proliferating tumor cells and an increase in bFGF and VEGF expression, reflecting the antiangiogenic effect of HSENDO. Intrapulmonary tumor induction caused death subsequent to metastatic disease. Systemic HSENDO application extended survival significantly. HSENDO was demonstrated to inhibit endothelial cell proliferation, migration and tube formation effectively. In vivo growth of s.c. transplanted tumors was delayed and survival extended by 32% and 69%, respectively, after intrapulmonary NSCLC induction.