Multimodality management of malignant pleural mesothelioma.

In this article, we explain the current trimodality approach used to treat malignant pleural mesothelioma. Our current approach employs extrapleural pneumonectomy as the cytoreductive procedure followed by combination chemoradiotherapy. Trimodality therapy was performed at the Dana-Farber Cancer Institute/Brigham and Women's Hospital Thoracic Oncology Program. From 1980 to 1995, we prospectively followed up a series of 120 patients with confirmed malignant pleural mesothelioma who underwent trimodality therapy. Two- and 5-year survival rates for the entire cohort were 45% and 22%, respectively. Survival rates were 65% and 27%, respectively, at 2 and 5 years for patients with epithelial histology. Patients with sarcomatous or mixed histology had the poorest prognosis, with 2- and 5-year survival rates of 20% and 0%, respectively. For patients with epithelial tumors and negative nodes, survival at 2 and 5 years was 74% and 39%, respectively. Extrapleural pneumonectomy in the context of trimodality therapy is a potential surgical option for a selected group of patients with malignant pleural mesothelioma.

Surgical staging and work-up of patients with diffuse malignant pleural mesothelioma.

The current modalities used to treat diffuse malignant pleural mesothelioma (DMPM) have not been evaluated in the setting of prospective, multi-institutional randomized trials for two reasons: DMPM is a rare disease, and there is a lack of a widely accepted and standarized staging system. Several staging systems have been proposed in an effort to categorize patients with DMPM into homogeneous groups. These efforts have been hampered by a lack of correlation between staging and survival. In our institutional experience, the Brigham staging system has been able to stratify patients with similar survival. This is an institutional experience that needs validation in a multi-institutional setting and, furthermore, in a trial based on stage-specific adjuvant therapies.

Extrapleural pneumonectomy in the setting of multimodality therapy for diffuse malignant pleural mesothelioma.

Diffuse malignant pleural mesothelioma, a rare disease, is characterized by an aggressive local behavior and scant response to therapy. The first series using single modality therapy showed failure in terms of survival and local control. More recently, multimodality therapy has been used against this disease with better results, but still with more room for substantial improvement. The current multimodality series reported are isolated, single-institutional experiences with different treatment schemes, using different staging systems, most of which have not been validated. There is an enormous need for multiinstitutional prospective trials to evaluate the current treatment schemes in light of the steady increase in the incidence of this lethal tumor. The trimodality therapy used at the Brigham and Women's Hospital for selected patients is described.

The protective effect of vein cuffed anastomoses is not mechanical in origin.

PURPOSE: Intimal hyperplasia (IH) is a proliferative process of vascular smooth muscle cells that occurs after an arterial injury, particularly at outflow anastomoses of prosthetic bypass grafts. IH causes stenosis that leads ultimately to graft flow reduction and thrombosis. We have demonstrated previously that vein cuff interposition between an expanded polytetrafluoroethylene (e-PTFE) graft and artery at distal anastomoses diminished IH formation in the arterial outflow as compared with noncuffed anastomoses. Improved long-term patency rates associated with the placement of an interposition vein cuff at the distal anastomosis of e-PTFE grafts to infrageniculate arteries have also been demonstrated clinically. This study examined the mechanical factors that may contribute to the protective effect of cuffed anastomoses. These factors include the expansibility of the vein cuff as compared with e-PTFE, as well as the angle of the cuffed anastomosis. METHODS: Compatible animals were selected by use of platelet aggregation studies. Nine dogs, group A, received a 4 mm e-PTFE graft plus a 1 cm long interposition vein cuff at the distal anastomosis in the left carotid artery. The same procedure was done on the right side, and in addition the vein cuff was encircled by an e-PTFE jacket incorporated into the anastomosis to prevent the expansion of the vein cuff with arterial pulsation. To study the effect of distal anastomotic angle and geometry on the formation of IH, five dogs, group B, received a 4 mm e-PTFE graft in both sides. On the left, the distal anastomosis was performed between the graft and the artery at an acute angle as it is commonly done when a bypass graft is placed. On the right side a 1 cm long, 6 mm diameter e-PTFE segment was interposed between the artery and the graft at a perpendicular angle. This geometry mimicked the right angle of a vein cuff-to-artery anastomosis. After 10 weeks the grafts were harvested, and the thickness of IH was measured with an ocular micrometer under light microscopy. RESULTS: In group A, one dog had bilateral graft thrombosis (12%), and these grafts were discarded. In the remaining eight dogs there was no statistically significant difference in the thickness of IH between the right (jacketed group) and the left side (nonjacketed/control group), showing that vein cuff expansibility did not play a role in protecting against the formation of IH. In group B, bilateral graft thrombosis occurred in four of five dogs (80%), suggesting that the perpendicular anastomotic angle was not protective. CONCLUSION: These results suggested that the protective effect of the vein cuff is not mechanical in origin.