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Biomedical subjects

John D Mitchell

Publications and source records attributed to John D Mitchell.

17 recordsLinked to original sources
PubMed2006

An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers.

BACKGROUND: To directly assess tumor oxygenation in resectable non-small cell lung cancers (NSCLC) and to correlate tumor pO2 and the selected gene and protein expression to treatment outcomes. METHODS: Twenty patients with resectable NSCLC were enrolled. Intraoperative measurements of normal lung and tumor pO2 were done with the Eppendorf polarographic electrode. All patients had plasma osteopontin measurements by ELISA. Carbonic anhydrase-IX (CA IX) staining of tumor sections was done in the majority of patients (n = 16), as was gene expression profiling (n = 12) using cDNA microarrays. Tumor pO2 was correlated with CA IX staining, osteopontin levels, and treatment outcomes. RESULTS: The median tumor pO2 ranged from 0.7 to 46 mm Hg (median, 16.6) and was lower than normal lung pO2 in all but one patient. Because both variables were affected by the completeness of lung deflation during measurement, we used the ratio of tumor/normal lung (T/L) pO2 as a reflection of tumor oxygenation. The median T/L pO2 was 0.13. T/L pO2 correlated significantly with plasma osteopontin levels (r = 0.53, P = 0.02) and CA IX expression (P = 0.006). Gene expression profiling showed that high CD44 expression was a predictor for relapse, which was confirmed by tissue staining of CD44 variant 6 protein. Other variables associated with the risk of relapse were T stage (P = 0.02), T/L pO2 (P = 0.04), and osteopontin levels (P = 0.001). CONCLUSIONS: Tumor hypoxia exists in resectable NSCLC and is associated with elevated expression of osteopontin and CA IX. Tumor hypoxia and elevated osteopontin levels and CD44 expression correlated with poor prognosis. A larger study is needed to confirm the prognostic significance of these factors.

Adenocarcinoma↗
PubMed2006

Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial.

BACKGROUND: Little prospective, multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality. METHODS: Prospectively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a randomized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. RESULTS: Of the 1,111 patients randomized, 1,023 were included in the analysis. Median age was 68 years (range, 23 to 89 years); 52% were men. Lobectomy was performed in 766 (75%) and pneumonectomy in 42 (4%). Pathologic stage was IA in 424 (42%), IB in 418 (41%), IIA in 37 (4%), IIB in 97 (9%), and III in 45 (5%). Lymph node sampling was performed in 498 patients and lymph node dissection in 525. Operative mortality was 2.0% (10 of 498) for lymph node sampling and 0.76% (4 of 525) for lymph node dissection. Complications occurred in 38% of patients in each group. Lymph node dissection had a longer median operative time and greater total chest tube drainage (15 minutes, 121 mL, respectively). There was no difference in the median hospitalization, which was 6 days in each group (p = 0.404). CONCLUSIONS: Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer. These data from a current, multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future.

Adult↗
PubMed2006

Anastomotic leak after esophagectomy.

Anastomotic leaks continue to be a source of considerable morbidity and mortality after esophageal resection. Careful attention to the contributing factors to the development of a leak, particularly conduit ischemia and anastomotic technique, can reduce the incidence of anastomotic complications postoperatively. Selective management of leaks, including non-operative treatment when indicated, will maximize the chance for a successful outcome.

Anastomosis, Surgical↗
PubMed2005

Oligoclonal CD4+ T cells in the lungs of patients with severe emphysema.

RATIONALE: Within the lungs of patients with severe emphysema, inflammation continues despite smoking cessation. Foci of T lymphocytes in the small airways of patients with emphysema have been associated with disease severity. Whether these T cells play an important role in this continued inflammatory response is unknown. OBJECTIVE: The aim of this study was to determine if T cells recruited to the lungs of subjects with severe emphysema contain oligoclonal T-cell populations, suggesting their accumulation in response to antigenic stimuli. METHODS: Lung T-cell receptor (TCR) Vbeta repertoire from eight patients with severe emphysema and six control subjects was evaluated at the time of tissue procurement (ex vivo) and after 2 weeks of culture with interleukin 2 (in vitro). Junctional region nucleotide sequencing of expanded TCR-Vbeta subsets was performed. RESULTS: No significantly expanded TCR-Vbeta subsets were identified in ex vivo samples. However, T cells grew from all emphysema (n = 8) but from only one of the control lung samples (n = 6) when exposed to interleukin 2 (p = 0.0013). Within the cultured cells, seven major CD4-expressing TCR-Vbeta subset expansions were identified from five of the patients with emphysema. These expansions were composed of oligoclonal populations of T cells that had already been expanded in vivo. CONCLUSION: Severe emphysema is associated with inflammation involving T lymphocytes that are composed of oligoclonal CD4+ T cells. These T cells are accumulating in the lung secondary to conventional antigenic stimulation and are likely involved in the persistent pulmonary inflammation characteristic of severe emphysema.

Adult↗
PubMed2005

Completion pneumonectomy for chronic mycobacterial disease.

OBJECTIVE: Patients with persistent pulmonary infections from mycobacterial disease present a difficult clinical challenge. These individuals typically have poor pulmonary function, malnutrition, and other comorbidities, and few guidelines exist regarding optimal therapy. We report our experience with completion pneumonectomy as part of a multidisciplinary treatment program for patients with recurrent, persistent mycobacterial disease. METHODS: During a 9-year period, 26 consecutive patients underwent completion pneumonectomy for mycobacterial disease. All patients underwent intensive, guided preoperative antibiotic therapy and aggressive nutritional supplementation. Complete surgical resection of the remaining destroyed or infected lung tissue was performed, often through an extrapleural dissection with intrapericardial ligation of vessels. Vascularized tissue flaps were used whenever possible to buttress the bronchial stump closure. Postoperative management consisted of a multidisciplinary approach, with ongoing antibiotic and nutritional therapy. RESULTS: The primary organisms were Mycobacterium avium complex (n = 15), Mycobacterium tuberculosis (n = 5), Mycobacterium abscessus (n = 3), Mycobacterium xenopi (n = 2), and Mycobacterium chelonae (n = 1). Operative mortality was 23% (6/26): respiratory failure or adult respiratory distress syndrome in 2 cases, sepsis in 2, bronchopleural fistula in 1, and pulmonary embolism in 1. Significant morbidity occurred in 46% (12/26). Among the 17 long-term survivors, sputum conversion or discontinuation of medications was achieved in 14 (82%). Mean length of follow-up was 45 months (range 4-105 months). CONCLUSION: Completion pneumonectomy remains an important component of therapy in patients with mycobacterial disease who have had failure of previous therapy. Although associated with significant risks, successful outcomes can be achieved with an organized, multidisciplinary approach and careful postoperative follow-up.

Adult↗
PubMed2005

Preoperative pulmonary evaluation of the thoracic surgical patient.

Fig. 2 is an algorithm for the preoperative pulmonary evaluation of the lung resection candidate. Patients should undergo routine spirometry and diffusion capacity testing. If the FEV1 and DLCO are greater than 80% predicted, no further study is needed. When these parameters are less than 80%, some estimation of postoperative function is likely needed, taking into account the proposed resection. Patients with ppoFEV1 or ppoDLCO less than 40% are at increased risk of perioperative complications or death and should undergo formal exercise testing. A VO2max or ppoVO2max less than 10 mL/kg/min is associated with prohibitive risk for anatomic lung resection, and alternative treatment modalities should be considered.

Algorithms↗
PubMed2005

Adjuvant chemotherapy for resected non-small-cell lung cancer.

Because of the high rate of distant disease recurrence, the 5-year survival of patients who have undergone complete surgical resection of localized non-small-cell lung cancer (NSCLC) is approximately 50%. Initial results from early studies of adjuvant postoperative chemotherapy reported an adverse effect of alkylating agent and older chemotherapy regimens on survival. Cisplatin-based combinations were the first to show a survival advantage. A 1995 meta-analysis of these studies suggested a 13% reduction in the hazard ratio for death (HR = 0.87), leading to a 5% survival benefit at 5 years. Still, these trials involved limited numbers of patients (N = 1,394), and the results failed to reach statistical significance (P = .08). Of the five largest subsequent randomized trials of platinum-based adjuvant therapy, three showed a significant survival advantage. Although it is impossible to determine the reasons for the differing outcomes of these studies, several key features distinguish them, and the data suggest that medically fit patients with resected stage IB or II NSCLC should be offered chemotherapy with a platinum/new drug combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Chylothorax after heart/lung transplantation.

Chylothorax is a potentially serious complication of lung and heart-lung transplantation. This article describes the clinical course of chylothorax in 3 heart-lung allograft recipients. We discuss management options, including dietary modifications, octreotide infusion, thoracic duct ligation and embolization, and surgical pleurodesis. In addition, we describe the novel use of aminocaproic acid to reduce lymph flow. We propose a multidisciplinary approach for the management of chylothorax that includes both medical and surgical options.

Adult↗
PubMed2003

Solitary fibrous tumor of the pleura.

Solitary fibrous tumors of the pleura are an uncommon but increasingly recognized neoplasm derived from mesenchymal cells located in the submesothelial lining of the pleural space. They may be differentiated from mesotheliomas and other pleural tumors due to unique immunohistochemical characteristics. The vast majority of these tumors are benign, and complete surgical resection remains the mainstay of therapy for both the benign and malignant variants. In this review, the clinical presentation, radiologic features, histologic findings, and treatment options for this tumor are described.

Cytogenetic Analysis↗
PubMed2003

Carinal resection and reconstruction.

Successful outcomes for carinal resection and reconstruction depend upon many factors. Careful patient selection for patients who can tolerate the physiologic effects of the operation cannot be underestimated. Understanding the safe limits of resection, the technical details of airway reconstruction, and ongoing improvements in intraoperative and postoperative care should minimize the morbidity and mortality rates previously reported with this procedure. In addition, further work from institutions with considerable experience in carinal resection is needed to better define the long-term outcome for patients with bronchogenic carcinoma in close proximity to or involving the carina. Prior studies have suggested reasonable survival rates can be expected in the absence of involved mediastinal nodes or distant metastatic disease.

Bronchi↗
PubMed2002

Massive pleural endometriosis.

We present a patient who was referred to our thoracic surgical service with a massive, loculated right pleural effusion accompanied by significant ascites. Thoracotomy and decortication were required and pleural biopsy led to a diagnosis of endometriosis. Aggressive medical therapy was subsequently initiated but hysterectomy with bilateral oophorectomy was required due to poor symptom control and the inability to rule out a neoplastic process. There are less than 15 reported cases of endometriosis presenting with both pleural effusion and ascites. Thoracic surgeons presented with such a scenario should be cognizant of this pathological entity.

Adult↗
PubMed2002

Assay of tracheal pepsin as a marker of reflux aspiration.

OBJECTIVES: Aspiration of gastric contents is a relatively common cause of acute and chronic pulmonary disease. However, a reliable method of diagnosing recurrent aspiration is currently lacking. The aim of this study was to determine whether the presence of gastric pepsin in tracheal aspirates of infants and children might be used as a reliable marker of the microaspiration of refluxed gastric contents. METHODS: Ninety-eight children undergoing general anesthesia and tracheal intubation participated in the study. Sixty-four of 98 children underwent endoscopy for clinically significant gastroesophageal reflux. Thirty-four children from routine operative lists were nonreflux controls. These two groups were further subdivided based on the presence or absence of associated respiratory symptoms. After endotracheal intubation, tracheal aspirates were obtained and subsequently assayed for gastric pepsin using a fluoroscein isothiocyanate casein. RESULTS: Pepsin was detected in 7 of 27 children with reflux symptoms alone and in 7 of 8 of those with chronic respiratory symptoms. In addition, pepsin was present in 31 of 37 children with a history of both reflux and chronic respiratory symptoms. Tracheal pepsin was not detected in any of the 26 children without gastroesophageal reflux or respiratory symptoms. Tracheal pepsin was found significantly more frequently in children with reflux symptoms than in those without, particularly in children with both reflux and respiratory problems. CONCLUSION: Tracheal pepsin assay as a reliable marker of gastroesophageal reflux aspiration.

Biomarkers↗
PubMed2002

Fat laden macrophages in tracheal aspirates as a marker of reflux aspiration: a negative report.

OBJECTIVES: Refluxed gastric material aspirated into the lungs is an important cause of acute and chronic pulmonary disease. Currently, the presence of fat-laden macrophages (FLM) in tracheobronchial secretions of children is a conventional marker for reflux aspiration. However, this assay is limited by its apparent lack of specificity. The aim of this study was to reevaluate the role of this assay in diagnosing reflux aspiration. METHODS: The tracheal aspirates of sixty-four consecutive children with clinically significant gastroesophageal reflux undergoing upper gastrointestinal endoscopy under general anesthesia, and 34 other children from the routine operative schedule were evaluated. Both groups were further subdivided on the basis of presence or absence of associated respiratory symptoms. After intubation, tracheal aspirates were collected, fixed, and stained for FLM. By grading the amount of intracellular fat present, a semiquantitative lipid index was computed. Tracheal aspirates with a lipid index of 100 or greater were considered positive. RESULTS: Twenty-four of the 64 children with reflux symptoms and 14 of 34 children without reflux symptoms were positive for FLM. Sixteen of 37 children with both gastroesophageal reflux and respiratory symptoms and 10 of 26 children negative for both tested positive for FLM. The mean lipid index of the subgroup of children with both reflux and respiratory symptoms was not significantly different from that of the subgroup that was negative for both conditions. Despite computing a semiquantitative lipid index, an index of 100 or greater only had a sensitivity of 38% and specificity of 59%. CONCLUSION: Assay of FLM in the tracheal aspirates of children considered at risk of reflux aspiration is not a sensitive or specific as a marker for reflux aspiration.

Biomarkers↗
PubMed2002

Role of video-assisted thoracoscopic surgery and classic thoracotomy in lung cancer management.

Lung cancer is the leading cause of cancer-related death worldwide. For patients diagnosed with early-stage lung cancer, complete surgical resection remains the best hope for cure. Limited resections are avoided when possible because of higher recurrence rates and potentially worse long-term survival. Traditionally, a posterolateral thoracotomy has been used to perform anatomic lung resections and mediastinal lymph node dissection for complete staging. More recently, the use of video-assisted thoracoscopic surgery has been introduced for the treatment of stage I lung cancers. Although thought minimally invasive and thus perceived as resulting in less postoperative pain and faster recovery, its acceptance has varied worldwide. Questions about training, cost containment, and oncologic principles prevail. In essence, the absolute indications and limitations of video-assisted thoracoscopic surgery for patients with lung cancer have yet to be defined.

Humans↗