Marcelo C. DaSilva

Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection

OBJECTIVE Local recurrence limits long-term survival in patients with malignant pleural mesothelioma. We investigated whether hyperthermic intraoperative cisplatin chemotherapy lavage affects the interval to recurrence and overall survival among patients with favorable prognostic factors. METHODS Using a preoperative risk assessment algorithm we had previously developed and validated, we retrospectively identified a cohort of patients treated with cytoreductive surgery from 2001 to 2009. The patients had epithelial histologic findings on biopsy and were characterized as having a low risk of early recurrence and death (ie, tumor volume ≤ 500 cm(3) and were either men with a hemoglobin level of ≥ 13 g/dL or were women). Those patients who had received hyperthermic intraoperative cisplatin chemotherapy were compared with a comparison group of those who had not. Fishers exact test was used to determine the balance of prognostic factors. The Kaplan-Meier method and log-rank tests were used to estimate and compare the interval to recurrence and overall survival. Cox proportional hazards regression was used for multivariate analysis. RESULTS The cohort criteria identified 103 patients: 72 who received hyperthermic intraoperative cisplatin chemotherapy and 31 who did not. The groups were balanced for prognostic factors, except for the use of neoadjuvant chemotherapy (more common in the comparison group). The hyperthermic intraoperative cisplatin chemotherapy group exhibited a significantly longer interval to recurrence (27.1 vs 12.8 months) and overall survival (35.3 vs 22.8 months) than the comparison group. The improved interval to recurrence and overall survival for the hyperthermic intraoperative cisplatin chemotherapy group were particularly evident among the subgroups of patients who had not received hemithoracic radiotherapy and who had pathologic stage N1 or N2 lymph node metastases. CONCLUSIONS A favorable outcome and minimal incremental morbidity support the incorporation of hyperthermic intraoperative cisplatin chemotherapy into multimodality treatment strategies for patients with low-risk epithelial malignant pleural mesothelioma.

Repeated and Aggressive Pulmonary Resections for Leiomyosarcoma Metastases Extends Survival

BACKGROUND Sarcoma frequently metastasizes to the lungs, and pulmonary metastasectomy is the only treatment modality that can provide a cure for these patients. We attempted to determine the clinicopathologic features and survival determinants of a common subset of patients who undergo pulmonary metastasectomy for leiomyosarcoma. METHODS All patients undergoing pulmonary metastasectomy at The Brigham and Womens Hospital from 1989 to 2004 were reviewed retrospectively. Analyzed variables included number, size, pathology, and location of metastases, age, gender, location of primary tumor, disease-free interval (DFI), surgical approach, margin status, adjuvant therapy, recurrence, number of metastasectomies, and disease-free and overall survival. RESULTS Eighty-two patients underwent pulmonary metastasectomy for metastases from sarcoma. Leiomyosarcoma was the most common histologic finding (n = 31; 38%). Fifteen patients with leiomyosarcoma (48%) underwent repeated pulmonary metastasectomy. Patients with leiomyosarcoma were more commonly female (77% versus 43%; p = 0.031), less frequently received chemotherapy for their primary tumor (48% versus 71%, p = 0.041), and presented with fewer number of pulmonary metastases than did patients with nonleiomyosarcoma metastases (1.9 ± 1.5 standard deviation [SD] versus 3.6 ± 4.4; p = 0.033). Although there was no difference in disease-free survival, patients with leiomyosarcoma demonstrated improved overall survival compared with those with nonleiomyosarcoma metastases (70 versus 24 months; p = 0.049). In multivariate analyses, the DFI from primary tumor resection to pulmonary metastases and the DFI from pulmonary metastasectomy to second pulmonary recurrence were identified as independent predictors of survival. CONCLUSIONS Leiomyosarcoma is a common subset of sarcomatous pulmonary metastases that behave more indolently compared with other pulmonary metastases from sarcoma. Long-term survival is achievable with an aggressive approach toward pulmonary metastasectomy and repeated pulmonary metastasectomy.

Left Atrial-Esophageal Fistula Repair after Radiofrequency Catheter Ablation for Atrial Fibrillation

Left atrial-esophageal fistula (LAEF) is a rare complication of radiofrequency ablation (RFA) procedures undertaken for atrial fibrillation (AF). This complication is associated with significant morbidity and mortality. Currently, there is no clear consensus on the appropriate management strategy. We report a case of a LAEF that developed in a patient 2 weeks after RFA for medication refractory AF. The patient underwent successful repair of the fistula through a left posterolateral thoracotomy, wherein the esophageal and atrial lesions were repaired primarily with an intercostal muscle flap and bovine pericardial patch to reinforce and prevent recurrence.

Diagnostic Workup of Lung Cancer

Lung cancer is the most frequent cause of mortality worldwide. According to recent estimates, 222,520 new cases of lung cancer (non-small cell and small cell combined) were diagnosed and 157,300 lung cancer-related deaths occurred in 2010 in the United States alone. The two major histologic types of lung cancer are small cell lung cancer and non-small cell lung cancer. The diagnosis and management of lung cancer requires a multidisciplinary approach.

A Phase I Trial of Surgical Resection and Intraoperative Hyperthermic Cisplatin and Gemcitabine for Pleural Mesothelioma

Introduction: The primary objective of this single‐institution phase I clinical trial was to establish the maximum tolerated dose of gemcitabine added to cisplatin and delivered as heated intraoperative chemotherapy after resection of malignant pleural mesothelioma. Methods: The extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators’ assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (range 175–225 mg/m2) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3‐plus‐3 design from 100 mg/m2 in 100‐mg increments. Results: From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. The median age of those completing treatment was 65 years (range 43–85 years), and 22 (21%) were female. In the EPP arm (n = 59), 31 patients (53%) had the epithelioid histologic type and the median radiographic tumor volume was 236 cm3 (range 16–4285 cm3). In the P/D arm (n = 41), 29 patients (71%) had the epithelioid histologic type and the median tumor volume was 79 cm3 (range 6–1107 cm3). The operative mortality rate was 2%, and 35 and 22 serious adverse events were encountered among 27 patients (46%) and 16 patients (39%) in the EPP and P/D arms, respectively. Dose‐limiting toxicity (grade 3 leukopenia) was observed in two patients who were receiving 1100 mg/m2 of gemcitabine, thus establishing the maximum tolerated dose at 1000 mg/m2, in combination with 175 mg/m2 of cisplatin. The median overall and recurrence‐free survival times in treated patients were 20.3 and 10.7 months, respectively. Conclusions: Combination cisplatin and gemcitabine heated intraoperative chemotherapy can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D.

Malignant and Benign Tumor-Induced Critical Limb Ischemia

Ischemia of the extremities is commonly treated in clinical practice. Most such occurrences are related to primary vascular—especially arterial—disease. However, on occasion, one may encounter upper and lower limb ischemia due to neoplastic processes. These patients may have either acute, subacute, or chronic slowly progressive benign or malignant lesions effecting the limb circulation.