Betty C. Tong

Thoracoscopic lobectomy has increasing benefit in patients with poor pulmonary function: a Society of Thoracic Surgeons Database analysis.

Objective:Using a national database, we asked whether video-assisted thoracoscopic surgery (VATS) lobectomy is beneficial in high-risk pulmonary patients. Background:Single-institution series demonstrated benefit of VATS lobectomy over lobectomy via thoracotomy in poor pulmonary function patients [FEV1 (forced expiratory volume in 1 second) or DLCO (diffusion capacity of the lung to carbon monoxide) <60% predicted]. Methods:The STS General Thoracic Database was queried for patients having undergone lobectomy by either thoracotomy or VATS between 2000 and 2010. Postoperative pulmonary complications included those defined by the STS database. Results:In the STS database, 12,970 patients underwent lobectomy (thoracotomy, n = 8439; VATS, n = 4531) and met inclusion criteria. The overall rate of pulmonary complications was 21.7% (1832/8439) and 17.8% (806/4531) in patients undergoing lobectomy with thoracotomy and VATS, respectively (P < 0.0001). In a multivariable model of pulmonary complications, thoracotomy approach (OR = 1.25, P < 0.001), decreasing FEV1% predicted (OR = 1.01 per unit, P < 0.001) and DLCO% predicted (OR = 1.01 per unit, P < 0.001), and increasing age (1.02 per year, P < 0.001) independently predicted pulmonary complications. When examining pulmonary complications in patients with FEV1 less than 60% predicted, thoracotomy patients have markedly increased pulmonary complications when compared with VATS patients (P = 0.023). No significant difference is noted with FEV1 more than 60% predicted. Conclusions:Poor pulmonary function predicts respiratory complications regardless of approach. Respiratory complications increase at a significantly greater rate in lobectomy patients with poor pulmonary function after thoracotomy compared with VATS. Planned surgical approach should be considered while determining whether a high-risk patient is an appropriate resection candidate.

Bladder carcinoma in a transplant recipient : evidence to implicate the BK human polyomavirus as a causal transforming agent

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are mostly limited to individuals who are immunosuppressed. In transplant recipients, BKV has been associated with ureteral stenosis, interstitial nephritis, and hemorrhagic cystitis. The role of BKV in the development of human tumors is intriguing but uncertain. BKV has been identified in various tumor types including urothelial carcinoma, but the ubiquitous presence of BKV as a latent infection has confounded efforts to validate any causal role in cancer development. We report the case of a simultaneous pancreas and kidney transplant recipient who developed BKV interstitial nephritis and carcinoma of the bladder with widespread metastases. High level expression of BKV large T antigen in the primary and metastatic carcinoma, but not in the nonneoplastic urothelium, implicates BKV as an etiologic agent in the development of this tumor.

Cellular and Physiological Effects of Arginine

Arginine is a semi-essential amino acid that is required during periods of maximal growth, severe stress, and injury. Arginine is a substrate for protein synthesis but also modulates cellular biochemical functions via conversion to a number of biologically active compounds. Arginine is utilized by a vast variety of metabolic pathways that produce a variety of biologically active compounds such as nitric oxide, creatine phosphate, agmatine, polyamines, ornithine, and citrulline. Arginine supply is primarily regulated by two enzyme systems: arginase (part of the urea cycle) and nitric oxide synthase. Arginine has many effects in the body that include modulation of immune function, wound healing, hormone secretion, vascular tone, insulin sensitivity, and endothelial function. Arginine mediates its effects via nitric oxide independent and dependent pathways. Nitric oxide modulates many cellular functions that include vascular tone, expression of adhesion molecules, leukocyte adhesion, and platelet aggregation. Arginine modulates the development of atherosclerotic cardiovascular disease, improves immune function in healthy and ill patients, stimulates wound healing in healthy and ill patients, and modulates carcinogenesis and tumor growth. Thus, arginine is a biologically active dietary compound with numerous physiologic and pharmacological activities.

Risk Factors for Morbidity After Lobectomy for Lung Cancer in Elderly Patients

BACKGROUND Studies evaluating risk factors for complications after lobectomy in elderly patients have not adequately analyzed the effect of using minimally invasive approaches. METHODS A model for morbidity including published preoperative risk factors and surgical approach was developed by multivariable logistic regression. All patients aged 70 years or older who underwent lobectomy for primary lung cancer without chest wall resection or airway procedure between December 1999 and October 2007 at a single institution were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Morbidity was measured as a patient having any perioperative complication. The impact of bias in the selection of surgical approach was assessed using propensity scoring. RESULTS During the study period, 338 patients older than 70 years (mean age, 75.7 +/- 0.2) underwent lobectomy (219 thoracoscopy, 119 thoracotomy). Operative mortality was 3.8% (13 patients) and morbidity was 47% (159 patients). Patients with at least one complication had increased length of stay (8.3 +/- 0.6 versus 3.8 +/- 0.1 days; p < 0.0001) and mortality (6.9% [11 of 159] versus 1.1% [2 of 179]; p = 0.008). Significant predictors of morbidity by multivariable analysis included age (odds ratio, 1.09 per year; p = 0.01) and thoracotomy as surgical approach (odds ratio, 2.21; p = 0.004). Thoracotomy remained a significant predictor of morbidity when the propensity to undergo thoracoscopy was considered (odds ratio, 4.9; p= 0.002). CONCLUSIONS Patients older than 70 years of age can undergo lobectomy for lung cancer with low morbidity and mortality. Advanced age and the use of a thoracotomy increased the risk of complications in this patient population.

Pulmonary Function Tests Do Not Predict Pulmonary Complications After Thoracoscopic Lobectomy

BACKGROUND Pulmonary function tests predict respiratory complications and mortality after lung resection through thoracotomy. We sought to determine the impact of pulmonary function tests upon complications after thoracoscopic lobectomy. METHODS A model for morbidity, including published preoperative risk factors and surgical approach, was developed by multivariable logistic regression. All patients who underwent lobectomy for primary lung cancer between December 1999 and October 2007 with preoperative forced expiratory volume in 1 second (FEV1) or diffusion capacity to carbon monoxide (Dlco) 60% or less predicted were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Pulmonary complications were defined as atelectasis requiring bronchoscopy, pneumonia, reintubation, and tracheostomy. RESULTS During the study period, 340 patients (median age 67) with Dlco or FEV1 60% or less (mean % predicted FEV1, 55+/-1; mean % predicted Dlco, 61+/-1) underwent lobectomy (173 thoracoscopy, 167 thoracotomy). Operative mortality was 5% (17 patients) and overall morbidity was 48% (164 patients). At least one pulmonary complication occurred in 57 patients (17%). Significant predictors of pulmonary complications by multivariable analysis for all patients included Dlco (odds ratio 1.03, p=0.003), FEV1 (odds ratio 1.04, p=0.003), and thoracotomy as surgical approach (odds ratio 3.46, p=0.0007). When patients were analyzed according to operative approach, Dlco and FEV1 remained significant predictors of pulmonary morbidity for patients undergoing thoracotomy but not thoracoscopy. CONCLUSIONS In patients with impaired pulmonary function, preoperative pulmonary function tests are predictors of pulmonary complications when lobectomy for lung cancer is performed through thoracotomy but not through thoracoscopy.

Outcomes of Video-Assisted Thoracoscopic Decortication

BACKGROUND Video-assisted thoracoscopic surgical decortication (VATSD) is widely used for treatment of early empyema and hemothorax, but conversion to open thoracotomy for decortication (OD) is more frequent in the setting of complex, chronic empyema. This study compared indications for and outcomes associated with VATSD and OD. METHODS The outcomes of 420 consecutive patients undergoing VATSD or OD for benign conditions from 1996 to 2006 were reviewed and compared with respect to baseline characteristics, preoperative management, and operative and postoperative course. Patients were analyzed on an intention-to-treat basis. RESULTS The cohort consisted of 326 VATSD and 94 OD patients. The conversion rate from VATSD to OD was 11.4%. The operative time and median in-hospital length of stay were shorter for the VATSD group: 97 vs 155 minutes (p < 0.001), and 15 vs 21 days (p = 0.03), respectively. The median postoperative length of stay was 7 days for the VATSD group vs 10 days for the OD group (p < 0.001). Significantly fewer postoperative complications occurred in the VATSD group in the following categories: atelectasis, prolonged air leak, reintubation, ventilator dependence, need for tracheostomy, blood transfusion, sepsis, and 30-day mortality. CONCLUSIONS Thoracoscopic decortication for empyema, complex pleural effusion, and hemothorax yields results that are at least equivalent to open decortication. Patients undergoing VATSD have fewer postoperative complications. The conversion and reoperation rates are low, suggesting that a thoracoscopic approach is an effective and reasonable first option for most patients with complex pleural effusions and empyema.

Aspergillus niger: an unusual cause of invasive pulmonary aspergillosis

Infections due to Aspergillus species cause significant morbidity and mortality. Most are attributed to Aspergillus fumigatus, followed by Aspergillus flavus and Aspergillus terreus. Aspergillus niger is a mould that is rarely reported as a cause of pneumonia. A 72-year-old female with chronic obstructive pulmonary disease and temporal arteritis being treated with steroids long term presented with haemoptysis and pleuritic chest pain. Chest radiography revealed areas of heterogeneous consolidation with cavitation in the right upper lobe of the lung. Induced bacterial sputum cultures, and acid-fast smears and cultures were negative. Fungal sputum cultures grew A. niger. The patient clinically improved on a combination therapy of empiric antibacterials and voriconazole, followed by voriconazole monotherapy. After 4 weeks of voriconazole therapy, however, repeat chest computed tomography scanning showed a significant progression of the infection and near-complete necrosis of the right upper lobe of the lung. Serum voriconazole levels were low–normal (1.0 μg ml−1, normal range for the assay 0.5–6.0 μg ml−1). A. niger was again recovered from bronchoalveolar lavage specimens. A right upper lobectomy was performed, and lung tissue cultures grew A. niger. Furthermore, the lung histopathology showed acute and organizing pneumonia, fungal hyphae and oxalate crystallosis, confirming the diagnosis of invasive A. niger infection. A. niger, unlike A. fumigatus and A. flavus, is less commonly considered a cause of invasive aspergillosis (IA). The finding of calcium oxalate crystals in histopathology specimens is classic for A. niger infection and can be helpful in making a diagnosis even in the absence of conidia. Therapeutic drug monitoring may be useful in optimizing the treatment of IA given the wide variations in the oral bioavailability of voriconazole.

Quality of life outcomes are equivalent after lobectomy in the elderly

OBJECTIVE Prospective analyses of quality of life in elderly patients after lobectomy are limited, yet surgeons often recommend suboptimal therapy to these patients on the basis of the belief that lobectomy is poorly tolerated. Surgical decision making in elderly patients with lung cancer is better informed when the benefits to survival and quality of life after lobectomy are understood. METHODS By using a validated quality of life instrument, 422 patients were prospectively assessed preoperatively and 3, 6, and 12 months after lobectomy. Outcomes were analyzed with respect to age (group 1: < 70 years and group 2: > or = 70 years). The outcome domains of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, global health, and pain in the chest were analyzed using a mixed model. The trend in quality of life was determined according to age. The Kaplan-Meier method was used for analysis of overall survival. RESULTS The mean age was 60.1 years in group 1 (N = 256) and 74.7 years in group 2 (N = 166). Baseline demographics and quality of life were similar except that group 2 had better emotional functioning scores and worse pain in the chest scores. Postoperatively, both groups demonstrated significant decreases in quality of life at 3 months. However, at 6 and 12 months, all domains had returned to baseline except physical functioning, which remained below baseline in group 2. Emotional functioning improved postoperatively for both groups. Overall survival at 5 years was not different between groups. CONCLUSION By using a validated quality of life assessment tool with measurements at baseline and serially after resection in a large patient population, this analysis quantifies the degree of impairment of quality of life after lobectomy and documents time to full recovery for both age groups.

A model for morbidity after lung resection in octogenarians

OBJECTIVE Age is an important risk factor for morbidity after lung resection. This study was performed to identify specific risk factors for complications after lung resection in octogenarians. METHODS A prospective database containing patients aged 80 years or older, who underwent lung resection at a single institution between January 2000 and June 2009, was reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed. Morbidity was measured as a patient having any perioperative event as defined by the Society of Thoracic Surgeons General Thoracic Surgery Database. A multivariable risk model for morbidity was developed using a panel of established preoperative and operative variables. Survival was calculated using the Kaplan-Meier method. RESULTS During the study period, 193 patients aged 80 years or older (median age 82 years) underwent lung resection: wedge resection in 77, segmentectomy in 13, lobectomy in 96, bilobectomy in four, and pneumonectomy in three. Resection was accomplished via thoracoscopy in 149 patients (77%). Operative mortality was 3.6% (seven patients) and morbidity was 46% (89 patients). A total of 181 (94%) patients were discharged directly home. Postoperative events included atrial arrhythmia in 38 patients (20%), prolonged air leak in 24 patients (12%), postoperative transfusion in 22 patients (11%), delirium in 16 patients (8%), need for bronchoscopy in 14 patients (7%), and pneumonia in 10 patients (5%). Significant predictors of morbidity by multivariable analysis included resection greater than wedge (odds ratio 2.98, p=0.006), thoracotomy as operative approach (odds ratio 2.6, p=0.03), and % predicted forced expiratory volume in 1s (odds ratio 1.28 for each 10% decrement, p=0.01). CONCLUSIONS Octogenarians can undergo lung resection with low mortality. Extent of resection, use of a thoracotomy, and impaired lung function increase the risk of complications. Careful evaluation is necessary to select the most appropriate approach in octogenarians being considered for lung resection.

TGF-β Promotes the Growth of Bovine Chondrocytes in Monolayer Culture and the Formation of Cartilage Tissue on Three-Dimensional Scaffolds

We have investigated the ability of transforming growth factor beta (TGF-beta) to promote the growth and differentiation of chondrocytes in monolayer and on three-dimensional scaffolds. Treatment of chondrocytes with TGF-beta and ascorbate individually stimulated the proliferation of bovine articular chondrocytes about 2-fold when cells were grown in monolayer culture: the combination of TGF-beta and ascorbate resulted in a 3-fold increase in cell number over a 72-h period. Peak stimulation with TGF-beta occurred at about 1.0 ng/ml: bFGF was slightly inhibitory in these assays. TGF-beta led to an increase in glycosaminoglycan synthesis as detected by Western blotting using anti-chondroitin sulfate antibodies. No significant change in collagen type II mRNA or protein was observed. When cells were grown on grown on three-dimensional scaffolds composed of polyglyocolic acid, TGF-beta treatment led to an increase in the size of the cartilage-like constructs produced. This was accompanied by increases in collagen and glycosaminoglycan deposition; immunohistochemical staining showed that the predominant collagen was type II. These results indicate that TGF-beta is capable of increasing the proliferation rate of chondrocytes in monolayer as well as increasing cartilage production on three-dimensional scaffolds and may find utility in the in vitro engineering of cartilage tissue.