[Show abstract][Hide abstract] ABSTRACT: Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC.
This investigation was a single-institution retrospective study of never and current smokers with NSCLC from 1975 to 2004. From an analytic cohort of 4,546 patients with NSCLC, we identified 724 never smokers and 3,822 current smokers. Overall, 1,142 patients underwent surgery with curative intent. For survival analysis by smoking status, hazard ratios (HRs) were estimated using Cox proportional hazard modeling and then further adjusted by other covariates.
Never smokers were significantly more likely than current smokers to be women (P < .01), older (P < .01), and to have adenocarcinoma (P < .01) and bronchioloalveolar carcinoma (P < .01). No statistically significant differences existed in stage distribution at presentation for the analytic cohort (P = .35) or for the subgroup undergoing surgery (P = .24). The strongest risk factors of mortality among patients with NSCLC who underwent surgery were advanced stage (adjusted hazard ratio, 3.43; 95% CI, 2.32-5.07; P < .01) and elevated American Society of Anesthesiologists classification (adjusted hazard ratio, 2.18; 95% CI, 1.40-3.40; P < .01). The minor trend toward an elevated risk of death on univariate analysis for current vs never smokers in the surgically treated group (hazard ratio, 1.20; 95% CI, 0.98-1.46; P = .07) was completely eliminated when the model was adjusted for covariates (P = .97).
Our findings suggest that smoking status at time of lung cancer diagnosis has little impact on the long-term survival of patients with NSCLC, especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers the prognosis is equally dismal.
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that most relapses in patients with esophageal cancer having neoadjuvant chemoradiation therapy would occur outside of the surgical and radiation fields.
Recurrence patterns, time to recurrence, and median survival were examined in 267 patients who had esophagectomy after neoadjuvant chemoradiation therapy at Johns Hopkins over 19 years.
Of 267 patients, 82 (30.7%) showed complete response to neoadjuvant therapy, with 108 (40.4%) and 77 (28.8%) showing partial response or no response, respectively. Recurrence developed in 84 patients (patients with complete response 18/82, 21.4%; patients with partial response 39/108, 36.1%; patients with no response 27/77, 35.1%; P = .055, respectively). Most patients had recurrences at distant sites (65/84;77.4%) regardless of pathologic response, and subsequent survival was brief (median 8.37 months). Median disease-free survival was short (10 months) and did not differ based on recurrence site for patients with partial response or no response, but was longer for patients with complete response with distant recurrence, whose median disease-free survival was 27.3 months (P = .008). By multivariate analysis, no other factor except for pathologic response to neoadjuvant therapy was associated with disease recurrence or death. Patients with partial response or no response were 1.97 and 2.23 times more likely to have recurrence than patients with complete response (P = .024 and P = .012, respectively).
Most esophageal cancer recurrences after neoadjuvant therapy and surgery are distant, and survival time after recurrence is short regardless of pathologic response. Fewer patients achieving complete response had recurrences, and distant recurrences in these patients manifest later than in patients showing partial response and those showing no response. Only pathologic response is significantly associated with disease recurrence, suggesting that tumor biology and chemosensitivity are critical in long-term patient outcome.
The Journal of thoracic and cardiovascular surgery 12/2009; 138(6):1309-17. · 3.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiac allotransplantation is subject to a number of chronic complications that may limit graft survival. These include allograft coronary artery disease, renal dysfunction, hypertension, and malignancy, which are largely due to the immuno-modulatory and adverse effects of transplant medications. Reoperation for native allograft disease progression is a rarer phenomenon. We report a case of aortic valve replacement for bicuspid aortic valve stenosis that occurred in a patient more than ten years after cardiac transplantation.
Interactive Cardiovascular and Thoracic Surgery 03/2009; 8(5):594-5. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although clinical trials of autologous whole bone marrow for cardiac repair demonstrate promising results, many practical and mechanistic issues regarding this therapy remain highly controversial. Here, we report the results of a randomized study of bone-marrow-derived mesenchymal stem cells, administered to pigs, which offer several new insights regarding cellular cardiomyoplasty. First, cells were safely injected by using a percutaneous-injection catheter 3 d after myocardial infarction. Second, cellular transplantation resulted in long-term engraftment, profound reduction in scar formation, and near-normalization of cardiac function. Third, transplanted cells were pre-prepared from an allogeneic donor and were not rejected, a major practical advance for widespread application of this therapy. Together, these findings demonstrate that the direct injection of cellular grafts into damaged myocardium is safe and effective in the perii-nfarct period. The direct delivery of cells to necrotic myocardium offers a valuable alternative to intracoronary cell injections, and the use of allogeneic mesenchymal stem cells provides a valuable strategy for cardiac regenerative therapy that avoids the need for preparing autologous cells from the recipient.
Proceedings of the National Academy of Sciences 09/2005; 102(32):11474-9. · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Valve-sparing operations for aortic root aneurysms are increasing in frequency, but techniques and results are still in evolution. We reviewed our experience with 65 patients (adults and children) who had this operation at our institution to determine early and late outcomes.
A retrospective clinical review was undertaken using hospital records, clinical and echocardiographic, computed tomography, magnetic resonance imaging data, and telephone interviews with patients and their physicians.
Between July 1994 and December 2002, 65 patients (46 adults and 19 children) underwent a valve-sparing operation for aortic root aneurysm. Forty-four of the patients had the Marfan syndrome; the remaining 21 had either a nonspecific connective tissue disorder (14 patients) or a miscellaneous disease process such as Ehlers-Danlos syndrome (7 patients). Fifty-eight (89%) had a David II (remodeling) procedure and 7 had a David I (reimplantation) procedure. The DePaulis "Valsalva graft" was used in six of the David I patients. There were no operative or hospital deaths; only one late death occurred in an adult due to salmonella meningitis. Overall, survival was 100% at one year and 98% at 3 and 5 years. Ten patients (7 adults and 3 children) developed significant late aortic insufficiency (AI). Nine of these patients had a David II procedure and in 8 of these cases, AI was secondary to significant late annular dilatation. One of the 10 patients developed late AI 8.2 years after a David I procedure; his AI was secondary to aortic leaflet extension and prolapse. Six of the 10 patients who developed significant late AI required aortic valve replacement (4 adults and 2 children). Freedom from late aortic valve replacement (AVR) in this series of 65 patients was 91% at 3 and 84% at 5 years. At the close of this study, 58 patients were New York Heart Association (NYHA) class I and 6 were NYHA class II; no patients were class III or IV. There were no episodes of endocarditis or clinically significant thromboembolism.
Valve-sparing operations provide satisfactory results for many patients with an aortic root aneurysm, but the David II remodeling procedure has a greater risk of late annular dilatation and AI. The David I reimplantation procedure utilizing the DePaulis Valsalva graft may obviate this problem.
The Annals of thoracic surgery 10/2004; 78(3):767-72; discussion 767-72. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Robotic surgical systems have greatly contributed to the advancement of minimally invasive endoscopic surgery. However, current robotic systems do not provide tactile or haptic feedback to the operating surgeon. Under certain circumstances, particularly with the manipulation of delicate tissues and suture materials, this may prove to be a significant irritation. We hypothesize that haptic feedback, in the form of sensory substitution, facilitates the performance of surgical knot tying. This preliminary study describes evidence that visual sensory substitution permits the surgeon to apply more consistent, precise, and greater tensions to fine suture materials without breakage during robot-assisted knot tying.
[Show abstract][Hide abstract] ABSTRACT: Ascending aortic aneurysms are unusual in children and have received little attention to develop guidelines for management. This study reviewed our experience with 50 children who have undergone aortic root replacement for ascending aortic aneurysm.
A retrospective clinical review was conducted using hospital charts and office records. Patients or their physicians were contacted for follow-up and recent echocardiograms were obtained and reviewed.
There was no operative or hospital mortality. Twenty-six children had aortic root replacement with a composite graft, 10 patients had replacement with a homograft aortic root, and 14 patients had a David II valve-sparing procedure. Factors related to late morbidity and mortality were analyzed. Long-term results were excellent in the 26 children receiving a composite graft. Twenty-three of these children were New York Heart Association class I (19) or II (4) at study closure. There were 3 late deaths (11, 16, and 17 years postoperative). Seven of 10 children receiving a homograft aortic root are long-term survivors and all 14 children having a valve-sparing procedure are alive. Generally, late results with the David II remodeling procedure have been good although 3 patients developed late aortic insufficiency and two required valve replacement.
Aortic root replacement in children with aneurysms has low operative risk and good long-term results. Composite grafts in particular carry a low risk of endocarditis, thromboembolism, and hemorrhagic events. Homografts are suitable for small patients but lack durability. Late results with the David II remodeling valve-sparing procedure in children have been compromised by late root dilatation.
The Annals of Thoracic Surgery 02/2004; 77(1):168-76. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular surgery requiring cardiopulmonary bypass (CPB) is frequently complicated by postoperative lung injury. Bronchial artery (BA) blood flow has been hypothesized to attenuate this injury. The purpose of the present study was to determine the effect of BA blood flow on CPB-induced lung injury in anesthetized pigs. In eight pigs (BA ligated) the BA was ligated, whereas in six pigs (BA patent) the BA was identified but left intact. Warm (37 degrees C) CPB was then performed in all pigs with complete occlusion of the pulmonary artery and deflated lungs to maximize lung injury. BA ligation significantly exacerbated nearly all aspects of pulmonary function beginning at 5 min post-CPB. At 25 min, BA-ligated pigs had a lower arterial Po(2) at a fraction of inspired oxygen of 1.0 (52 +/- 5 vs. 312 +/- 58 mmHg) and greater peak tracheal pressure (39 +/- 6 vs. 15 +/- 4 mmHg), pulmonary vascular resistance (11 +/- 1 vs. 6 +/- 1 mmHg x l(-1) x min), plasma TNF-alpha (1.2 +/- 0.60 vs. 0.59 +/- 0.092 ng/ml), extravascular lung water (11.7 +/- 1.2 vs. 7.7 +/- 0.5 ml/g blood-free dry weight), and pulmonary vascular protein permeability, as assessed by a decreased reflection coefficient for albumin (sigma(alb); 0.53 +/- 0.1 vs. 0.82 +/- 0.05). There was a negative correlation (R = 0.95, P < 0.001) between sigma(alb) and the 25-min plasma TNF-alpha concentration. These results suggest that a severe decrease in BA blood flow during and after warm CPB causes increased pulmonary vascular permeability, edema formation, cytokine production, and severe arterial hypoxemia secondary to intrapulmonary shunt.
[Show abstract][Hide abstract] ABSTRACT: Pharmacological openers of mitochondrial ATP-sensitive potassium (mitoKATP) channels have been shown to mimic ischemic preconditioning (IPC) in both the brain and myocardium. We hypothesized that similar endogenous mechanisms exist in the spinal cord and that diazoxide, a potent mitoKATP opener, could reduce neurologic injury after aortic cross-clamping in a model of spinal cord ischemia.
The infra-renal aorta was cross-clamped in 45 male New Zealand white rabbits for 20 minutes. Control animals received no pretreatment. Diazoxide-treated animals were dosed (5 mg/kg) 15 minutes before cross-clamp. A third group underwent 5 minutes of IPC 30 minutes before cross-clamp. Two groups received KATP antagonists, 5-hydroxydecanoic acid (5-HD, 20 mg/kg) or glibenclamide (1.0 mg/kg), before diazoxide administration. Systemic hypotension was induced in a final group with excess isoflurane. Tarlov Scoring was used to assess neurologic function at 24 and 48 hours, after which, the spinal cords were procured for histopathological analysis.
Tarlov scoring demonstrated marked improvement in the Diazoxide group compared with control at 24 hours (p < 0.02) and 48 hours (p < 0.009). Moreover, no further neurologic injury occurred in this group at 7 days. IPC-treated animals showed neurologic improvement but were not significantly different from controls. Further, administration of glibenclamide was effective in antagonizing diazoxide's protective effect.
Administration of diazoxide resulted in significant improvement in neurologic outcome in this model. This protective effect improved outcome at both early and late time points. Further, the antagonistic effect of glibenclamide implicates diazoxide's ATP-dependent potassium channel agonism as the mechanism of protection. Overall, this study suggests that diazoxide may be useful in the prevention of neurologic injury after thoracic aneurysm surgery.
The Annals of Thoracic Surgery 10/2002; 74(3):838-44; discussion 844-5. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The increasingly severe shortage of donor hearts has prompted a liberalization of what is considered an acceptable donor heart. The use of marginally acceptable organs has increased in recent years. Although these marginal donors have proved effective, there still remains a tremendous shortage of donors to treat the large number of patients who are candidates for cardiac transplantation. Further use of marginal donors is limited by the requirement to assume immediate and full support of the circulation. New strategies are required to increase donor organ use even further. The authors developed a model of heterotopic abdominal heart transplant (HAHT) to investigate the possibility of using marginal donor hearts to expand the donor pool for cardiac transplantation. The authors' goal was to show that HAHT was technically feasible and could potentially function as auxiliary circulatory support in the setting of low cardiac output. The hemodynamic and metabolic consequences of a HAHT were investigated in a pilot study that provides proof of concept and lays the groundwork for future investigations.
Current Opinion in Cardiology 04/2002; 17(2):145-51. · 2.56 Impact Factor