Matthew G. Blum

Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer

PURPOSE This study evaluated the efficacy and safety of pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed and bevacizumab in patients with chemotherapy-naive stage IIIB (effusion) or stage IV nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients received pemetrexed 500 mg/m(2), carboplatin area under the concentration-time curve of 6, and bevacizumab 15 mg/kg every 3 weeks for six cycles. For patients with response or stable disease, pemetrexed and bevacizumab were continued until disease progression or unacceptable toxicity. RESULTS Fifty patients were enrolled and received treatment. The median follow-up was 13.0 months, and the median number of treatment cycles was seven (range, one to 51). Thirty patients (60%) completed > or = six treatment cycles, and nine (18%) completed > or = 18 treatment cycles. Among the 49 patients assessable for response, the objective response rate was 55% (95% CI, 41% to 69%). Median progression-free and overall survival rates were 7.8 months (95% CI, 5.2 to 11.5 months) and 14.1 months (95% CI, 10.8 to 19.6 months), respectively. Grade 3/4 hematologic toxicity was modest-anemia (6%; 0), neutropenia (4%; 0), and thrombocytopenia (0; 8%). Grade 3/4 nonhematologic toxicities were proteinuria (2%; 0), venous thrombosis (4%; 2%), arterial thrombosis (2%; 0), fatigue (8%; 0), infection (8%; 2%), nephrotoxicity (2%; 0), and diverticulitis (6%; 2%). There were no grade 3 or greater hemorrhagic events or hypertension cases. CONCLUSION This regimen, involving a maintenance component, was associated with acceptable toxicity and relatively long survival in patients with advanced nonsquamous NSCLC. These results justify a phase III comparison against the standard-of-care in this patient population.

Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis.

Benign metastasizing leiomyoma is a rare condition affecting women with a history of uterine leiomyomata and is characterized by multiple histologically benign pulmonary smooth muscle tumors. Speculations on its pathogenesis include a benign uterine leiomyoma colonizing the lung, a metastatic low-grade uterine leiomyosarcoma, and primary pulmonary leiomyomatosis. To elucidate its pathogenesis, we analyzed the clinical, pathological and immunohistochemical features, clonality, and telomere length of multiple lung and uterine tumors in three patients with benign metastasizing leiomyoma. In all cases, pulmonary tumors had benign histology and immunohistochemical profiles (estrogen receptor positive, progesterone receptor positive, and very low proliferative index) identical to uterine leiomyoma. In eight tumors from three patients, clonality was assessed by analyzing the variable length of the polymorphic CAG repeat sequence within the human androgen receptor gene. In the two informative patients pulmonary and uterine tumors showed identical patterns of androgen receptor allelic inactivation, indicating that they were clonal. The telomere length measured by fluorescence in situ hybridization in pulmonary leiomyomas of all three patients were either long or very long and were identical to the uterine counterparts, indicating significant telomere shortening is not a crucial step for developing metastases. Our evidence supports the notion that benign metastasizing leiomyoma is clonally derived from benign-appearing uterine leiomyomas.

Clinical statement on the role of the surgeon and surgical issues relating to computed tomography screening programs for lung cancer

Division of Thoracic Surgery, National Cancer Institute, Pascale Foundation, Naples, Italy (GR); Division of Thoracic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota (MSA); Division of Thoracic Surgery, New York Presbyterian–Weill Cornell Medical Center, New York, New York (NKA); Division of Thoracic Surgery, National Cancer Institute, Tokyo, Japan (HA); General Thoracic Surgery, Penrose Cardiothoracic Surgery, Colorado Springs, Colorado (MGB); Department of Thoracic Surgery, Yale University, New Haven, Connecticut (FCD); Arkansas Department of Health, Little Rock, Arkansas (CMD); Department of Thoracic Surgery, Institut Mutualiste Montsouris, Paris, France (DG); Division of Thoracic Surgery, Foothills Medical Center, University of Calgary, Calgary, Canada (SCG); Department of Thoracic Surgery, Brigham and Women’s Hospital, Boston, Massachusetts (MTJ); Division of Cardiothoracic Surgery, University of Colorado Denver School of Medicine, Aurora, Colorado (JDM); Sentara Thoracic Surgery Center, Mid-Atlantic Cardiothoracic Surgeons, Ltd, Norfolk, Virginia (JRN); Department of Thoracic and Vascular Surgery, University Hospital of Antwerp, Antwerp, Belgium (PEVS); Division of Thoracic Surgery, University of Toronto, Toronto, Canada (TKW); and Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington (DEW)

Adenocarcinoma of the gastroesophageal junction after bariatric surgery

BACKGROUND The development of upper gastrointestinal malignancies after bariatric surgery has not been well characterized. Our objective was to review the experience of patients with distal esophageal cancer that was diagnosed after bariatric surgery. METHODS A retrospective review was conducted to identify patients who had undergone bariatric surgery (1999 to 2006) and who later developed high-grade dysplasia or adenocarcinoma of the distal esophagus. RESULTS Three patients (of 2,875 [0.1%]) developed esophageal cancer: 2 after Roux-en-Y gastric bypass and 1 after vertical banded gastroplasty. All three patients had complaints of reflux, and two were treated with esophagectomy. The third patient presented with invasive carcinoma and died 2 years after diagnosis. CONCLUSIONS Our findings emphasize the importance of precise endoscopic evaluation before bariatric surgery in patients with gastroesophageal reflux disease (GERD), of the necessity for continuing postsurgical surveillance in patients with known Barretts esophagitis, and of early evaluation in patients who develop new symptoms of GERD after bariatric surgery.

Mucosal Tube Technique for Creation of Esophageal Anastomosis After Esophagectomy

BACKGROUND The definitive treatment of esophageal cancer remains surgical resection. Morbidity and mortality are highly influenced by the success of the anastomosis created in the reconstruction of the resected esophagus. The results of an anastomotic technique that creates an esophageal mucosal tube are analyzed. METHODS The medical records of all patients undergoing esophagectomy at a single institution by 3 surgeons between January 2002 and July 2008 were reviewed. Patients who underwent a 2-layer, hand-sewn, esophageal anastomosis using a mucosal tube were included. The unique aspect of the anastomosis was the creation of an esophageal mucosal tube that facilitates a tension-free, precise mucosal approximation. RESULTS Of the 61 patients who underwent esophageal reconstructions (60 gastric, 1 colonic), 49 (80%) had a diagnosis of esophageal neoplasm. Of those with cancer, 20 (41%) had neoadjuvant therapy before the resection. Two patients presented with perforation. The anastomoses were intrathoracic in 57 of 61 (93%) and cervical in 4 cervical. There were no operative deaths. All patients underwent contrast study at an average of 5 days postoperatively. The anastomotic leak rate was 2% (1 of 61). Postoperative dilations (mean, 1.3 dilations) were done in 12 of 61 patients (20%), using a low symptom threshold for endoscopy and dilation. CONCLUSIONS The use of the esophageal mucosal tube and 2-layer anastomosis is a robust technique that results in a low leak rate. Strictures are minimal and easily dilated if they occur. Use of a gastrotomy larger than 2.5 cm may decrease stricture rates.

Acute Superior Vena Cava Occlusion After Stenting of Tracheoesophageal Fistula

Acute development of superior vena cava syndrome is unusual. This report describes a patient who suddenly presented with a superior vena cava obstruction after esophageal and tracheal stenting for a malignant tracheoesophageal fistula. Stenting of the superior vena cava rapidly alleviated the obstruction and resulted in resolution of symptoms.