Faculty Bibliography

BACKGROUND: Radical pleurectomy (RP) for mesothelioma is often considered either technically unfeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma. METHODS: Thirty-eight patients (42-81 years) underwent RP-PDT. Thirty five of 38 (92%) patients also received systemic therapy. Standard statistical techniques were used for analysis. RESULTS: Thirty seven of 38 (97%) patients had stage III/IV cancer (according to the American Joint Committee on Cancer [AJCC manual 7th Edition, 2010]) and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was 1 postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) patients with epithelial subtypes, and 6.8 months for the 7/38 (18%) patients with nonepithelial subtypes. Median progression-free survival (PFS) was 9.6, 15.1, and 4.8 months, respectively. The median survival and PFS for the 20/31 (64%) patients with N2 epithelial disease were 31.7 and 15.1 months, respectively. CONCLUSIONS: It was possible to achieve a macroscopic complete resection using lung-sparing surgery in 97% of these patients with stage III/IV disease. The survival we observed with this approach was unusually long for the patients with the epithelial subtype but, interestingly, the PFS was not. The reason for this prolonged survival despite recurrence is not clear but is potentially related to preservation of the lung or some PDT-induced effect, or both. We conclude that the results of this lung-sparing approach are safe, encouraging, and warrant further investigation.

BACKGROUND: Post-lung-transplant bronchial stenosis (TBS) may cause significant morbidity and mortality. Although often transiently relieved by balloon bronchoplasty, stents may be required for long-term airway patency. We report a series of lung transplant patients in whom a silicone Y-stent was placed at the secondary carina for long-standing relief of post-transplant-airway stenosis. METHODS: Six lung transplant patients received 10 silicone Y-stents in the secondary carina over the past 18 months for post-transplant-bronchial stenosis. All patients failed other interventional therapeutic procedures including balloon bronchoplasty and/or conventional stenting before secondary carina Y-stent placement. Patient data include 12 months' follow-up after Y-stent insertion. The number of procedures and the interval between procedures was examined before and after secondary carina silicone Y-stent placement. RESULTS: There was a significantly prolonged therapeutic effect accomplished in these patients after secondary carina Y-stent placement with the exception of 1 patient. When stents were tolerated by the patient, the mean number of procedures before secondary carina Y-stent insertion was 15.6, but only 4.8 after Y-stent insertion. The number of days between procedures was 24.5 days before the Y-stent insertion and 85.8 days after the Y-stent insertion. There were no complications in any patient during secondary carina Y-stent insertion. CONCLUSIONS: Secondary carina silicone Y-stent placement in TBS decreased the number of therapeutic procedures and provided longer-lasting results in most posttransplant patients who required multiple prior procedures for TBS.

PURPOSE: Listeria monocytogenes (Lm)-based vaccines stimulate both innate and adaptive immunity. ANZ-100 is a live-attenuated Lm strain (Lm DeltaactA/DeltainlB). Uptake by phagocytes in the liver results in local inflammatory responses and activation and recruitment of natural killer (NK) and T cells, in association with increased survival of mice bearing hepatic metastases. The Lm DeltaactA/DeltainlB strain, engineered to express human mesothelin (CRS-207), a tumor-associated antigen expressed by a variety of tumors, induces mesothelin-specific T-cell responses against mesothelin-expressing murine tumors. These two phase I studies test ANZ-100 and CRS-207 in subjects with liver metastases and mesothelin-expressing cancers, respectively. EXPERIMENTAL DESIGN: A single intravenous injection of ANZ-100 was evaluated in a dose escalation study in subjects with liver metastases. Nine subjects received 1 x 10(6), 3 x 10(7), or 3 x 10(8) colony-forming units (cfu). CRS-207 was evaluated in a dose-escalation study in subjects with mesothelioma, lung, pancreatic, or ovarian cancers. Seventeen subjects received up to 4 doses of 1 x 10(8), 3 x 10(8), 1 x 10(9), or 1 x 10(10) cfu. RESULTS: A single infusion of ANZ-100 was well tolerated to the maximum planned dose. Adverse events included transient laboratory abnormalities and symptoms associated with cytokine release. Multiple infusions of CRS-207 were well tolerated up to 1 x 10(9) cfu, the determined maximum tolerated dose. Immune activation was observed for both ANZ-100 and CRS-207 as measured by serum cytokine/chemokine levels and NK cell activation. In the CRS-207 study, listeriolysin O and mesothelin-specific T-cell responses were detected and 37% of subjects lived >/=15 months. CONCLUSIONS: ANZ-100 and CRS-207 administration was safe and resulted in immune activation.

Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers