Biomedical subjects
Jonathan C Nesbitt
Publications and source records attributed to Jonathan C Nesbitt.
A training-testing approach to the molecular classification of resected non-small cell lung cancer.
PURPOSE: RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance. EXPERIMENTAL DESIGN: In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray. RESULTS: Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous. High alpha-actinin-4 expression was identified as highly correlated with poor prognosis. CONCLUSIONS: These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.
Long-term outcome of phase II trial evaluating chemotherapy, chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer.
PURPOSE: To evaluate the long-term outcome of chemotherapy, chemoradiotherapy, and surgery for patients with locoregionally advanced esophageal cancer. METHODS AND MATERIALS: Thirty-eight patients with locoregionally advanced esophageal cancer were entered into a Phase II study between November 1996 and October 1998 at the University of Texas M. D. Anderson Cancer Center. Patients initially received two cycles of chemotherapy with paclitaxel (200 mg/m(2)), 5-fluorouracil (750 mg/m(2)/d for 5 days), and cisplatin (15 mg/m(2)/d for 5 days), followed by chemoradiotherapy, consisting of radiation (45 Gy during 5 weeks) with 5-fluorouracil (300 mg/m(2)/d during radiation) and cisplatin (15 mg/m(2)/d for 5 days). Surgical resection was performed 4-6 weeks after the completion of the chemoradiotherapy. RESULTS: Most patients had adenocarcinoma (n = 32; 84%). Pretreatment endoscopic ultrasonography revealed T3 tumors in 33 patients (87%) and N1 disease in 25 patients (66%). Thirty-seven patients (97%) completed the planned chemotherapy and chemoradiotherapy, and 35 patients (92%) underwent surgery, with a 30-day mortality rate of 6% (2 of 35 patients). A pathologic complete response or microscopic residual carcinoma (<10% viable) was found in 25 (71%) of 35 patients and was associated with a disease-free survival rate of 72% at 3 years and 51% at 5 years. On the basis of an intention-to-treat analysis and a median potential follow-up of 58 months, the 3- and 5-year overall survival rate for all 38 patients was 63% and 39%, respectively. CONCLUSION: The long-term results of this study suggest that the strategy of induction chemotherapy followed by chemoradiotherapy and surgery is safe and warrants further evaluation in the treatment of patients with locoregionally advanced esophageal cancer.
Prevalence and clinical course of pleural effusions at 30 days after coronary artery and cardiac surgery.
The present prospective study was designed to determine the prevalence of pleural effusion at approximately 28 days after cardiac surgery and their subsequent course. This consecutive case study included 389 patients; 312 had only coronary artery bypass graft surgery (CABG) surgery, 37 had both valve and CABG surgery, and 40 had only valve surgery. Chest radiographs were obtained approximately 28 days postoperatively. Patients were subsequently contacted by telephone 3, 6, and 12 months postoperatively and questioned about the presence of fluid in their chest and related symptoms. The prevalence of pleural effusions in the patients undergoing only CABG surgery (63%) or CABG surgery plus valve surgery (62%) was significantly (p = 0.05) higher than that in the patients undergoing valve surgery only (45%). The prevalence of effusions occupying more than 25% of the hemithorax was 9.7%. The primary symptom associated with these larger effusions was dyspnea. Chest pain and fever were uncommon. Over the 12-month follow-up, the effusions tended to resolve. In conclusion, the prevalence of pleural effusions occupying more than 25% of the hemithorax is approximately 10%, 28 days postoperatively. These larger pleural effusions produce dyspnea but not chest pain or fever, and most of the effusions disappear gradually over the subsequent months.
Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
BACKGROUND: The prevention of major pulmonary events (MPEs) after pneumonectomy may minimize postoperative mortality rates. The purpose of this study was to identify preoperative and perioperative factors associated with the development of MPEs after pneumonectomy to help predict which patients are at increased risk for MPEs. METHODS: We retrospectively reviewed the medical records of all patients (n = 261) who underwent pneumonectomies between January 1990 and May 1999. We analyzed preoperative and perioperative risk factors, the primary end point of an MPE and the secondary end points of mortality (in-hospital or 30 days postprocedure), length of stay, and hospital charges. A postoperative MPE included only pneumonia or acute respiratory distress syndrome as defined by the Centers for Disease Control and the American and European Consensus Conference's established criteria. Simple atelectasis that did not progress to pneumonia or a documented aspiration was not included. RESULTS: Four patients died within 12 hours of operation; the records of the remaining 257 patients were analyzed. An MPE occurred in 33 (12.8%) of 257 patients; 16 (6.2%) of 257 patients died. A multivariate analysis performed on relevant variables showed that only the timing of smoking cessation (1 month or sooner before operation) was a significant predictor of an MPE. Age, side of pneumonectomy, and the use of preoperative chemotherapy or combined chemotherapy and radiation therapy were not significant predictors of an MPE. An MPE significantly increased the mortality rate 2.1% versus 39.3%, p < 0.001). CONCLUSIONS: Mortality after pneumonectomy increased significantly with the development of an MPE. Patients who continue to smoke within 1 month of operation are at an increased risk for developing an MPE. Interventions to minimize MPEs may minimize the mortality rate after pneumonectomy.