Bilateral versus Single Internal-Thoracic-Artery Grafts at 10 Years.

BACKGROUND: Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG. METHODS: We randomly assigned patients scheduled for CABG to undergo bilateral or single internal-thoracic-artery grafting. Additional arterial or vein grafts were used as indicated. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. RESULTS: A total of 1548 patients were randomly assigned to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group) and 1554 to undergo single internal-thoracic-artery grafting (the single-graft group). In the bilateral-graft group, 13.9% of the patients received only a single internal-thoracic-artery graft, and in the single-graft group, 21.8% of the patients also received a radial-artery graft. Vital status was not known for 2.3% of the patients at 10 years. In the intention-to-treat analysis at 10 years, there were 315 deaths (20.3% of the patients) in the bilateral-graft group and 329 deaths (21.2%) in the single-graft group (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.12; P=0.62). Regarding the composite outcome of death, myocardial infarction, or stroke, there were 385 patients (24.9%) with an event in the bilateral-graft group and 425 patients (27.3%) with an event in the single-graft group (hazard ratio, 0.90; 95% CI, 0.79 to 1.03). CONCLUSIONS: Among patients who were scheduled for CABG and had been randomly assigned to undergo bilateral or single internal-thoracic-artery grafting, there was no significant between-group difference in the rate of death from any cause at 10 years in the intention-to-treat analysis. Further studies are needed to determine whether multiple arterial grafts provide better outcomes than a single internal-thoracic-artery graft. (Funded by the British Heath Foundation and others; Current Controlled Trials number, ISRCTN46552265 .).

Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation that persists after the cessation of smoking. T cells have a major role in driving inflammation in patients with COPD and are activated by specific antigens to produce mediators, such as cytokines. The antigens that activate lung T cells have not been clearly defined. Nontypeable Haemophilus influenzae (NTHi) is the dominant bacterium isolated from the lungs of patients with COPD. OBJECTIVE: We sought to measure the response of lung tissue T cells to stimulation with NTHi. METHODS: We obtained lung tissue from 69 subjects having lobectomies for lung cancer. Of the group, 39 subjects had COPD, and 30 without COPD were classified as control subjects. The lung tissue was dispersed into single-cell suspensions and stimulated with live NTHi. Cells were labeled with antibodies for 5 important inflammatory mediators in patients with COPD and analyzed by using flow cytometry. RESULTS: NTHi produced strong activation of both TH cells and cytotoxic T cells in the COPD cohort. The COPD cohort had significantly higher levels of cells producing TNF-α, IL-13, and IL-17 in both T-cell subsets. When control subjects were divided into those with and without a significant smoking history and compared with patients with COPD, there was a progressive increase in the numbers of T cells producing cytokines from nonsmoking control subjects to smoking control subjects to patients with COPD. CONCLUSION: NTHi activates lung T cells in patients with COPD. This proinflammatory profibrotic response might be a key cause of inflammation in patients with COPD and has implications for treatment.

The value of post mortems in cardiac surgery: learning from the dead.

BACKGROUND: Little information is available regarding the role of post-mortem in cardiac surgery. The cause of death by clinical presumption can be misleading. The aim is evaluate the role of post-mortem following cardiac surgery by comparing clinically attributed causes of death versus post-mortem findings. METHODS: A total of 10,099 cardiac operations were performed over a seven-year period in a single institution in the United Kingdom. There were 363 (3.6%) deaths. The mean age at death was 71 with 66.7% male. Of these, 348 (95.9%) patients underwent a post-mortem examination. RESULTS: There was a significant disparity between presumed and actual causes of death in 78 (22.4%) patients. The commonest unrecognised cause of death was cardiac causes (21 patients, 6.0%). The most overestimated cause of death was multi-organ failure, which was incorrectly diagnosed as the cause of death in 28 patients (8.0%). CONCLUSIONS: Post-mortem can determine unsuspected diagnoses in a significant proportion of patients undergoing cardiac surgery. It plays an important role in cardiac surgery and remains essential for quality assessment in perioperative treatment.

Emphysema quantification in inflation-fixed lungs using low-dose computed tomography and 3He magnetic resonance imaging.

OBJECTIVE: To evaluate the use of inflation-fixed lung tissue for emphysema quantification with computed tomography (CT) and He magnetic resonance (MR) diffusion imaging. METHODS: Fourteen subjects representing a range of chronic obstructive pulmonary disease severity who underwent complete or lobar lung resection were studied. Computed tomographic measurements of lung attenuation and MR measurements of the hyperpolarized 3He apparent diffusion coefficient (ADC) in resected specimens fixed in inflation with heated formalin vapor were compared with measurements obtained before fixation. RESULTS: The mean (SD) CT emphysema indices were 56% (17%) before and 58% (19%) after fixation (P = 0.77; R = 0.76). Index differences correlated with differences in lung volume (R = 0.47). The mean (SD) 3He ADCs were 0.40 (0.15) cm/s before and 0.39 (0.14) cm/s after fixation (P = 0.03, R = 0.98). The CT emphysema index and the 3He ADC were correlated before (R = 0.89) and after fixation (R = 0.79). CONCLUSIONS: Concordance of CT and 3He MR imaging measurements in unfixed and inflation-fixed lungs supports the use of inflation-fixed lungs for quantitative imaging studies in emphysema.

Airway bypass improves the mechanical properties of explanted emphysematous lungs.

RATIONALE: By creating artificial communications through bronchial walls into the parenchyma of explanted lungs (airway bypass), we expect to decrease the amount of gas trapped and to increase the rate and volume of air expelled during forced expirations. OBJECTIVES: To describe the mechanism by which airway bypass improves the mechanical properties of the emphysematous lung. METHODS: Lung compartments and mechanics were measured before and after airway bypass, which was created by placement of three or four stent-supported fenestrations in 10 emphysematous lungs removed at transplantation surgery. MEASUREMENTS AND MAIN RESULTS: Minimal volume after passive deflation decreased by a mean of 1.54 L (range, 0.7-2.5 L) or 60% (range, 37-86%). Explanted VC increased by 1.30 L or 132% (range, 78-318%). Maximal expiratory flows and volumes increased. Flow resistance decreased. CONCLUSIONS: Because these data show that airway bypass improves the mechanics of breathing in severely emphysematous lungs in vitro, there is now strong empirical support that this procedure can improve ventilatory function in patients by reducing gas trapping and flow resistance.

Concomitant lung cancer resection and lung volume reduction surgery.

Patients who are offered concomitant surgery are highly selected and must satisfy the strict criteria set out for both LVRS and cancer surgery. Several evaluative processes have been reported for the selection of suitable patients. These various evaluative processes, together with the physical condition of the patient and the surgeon's experience, help to best select patients suitable for combined surgical resection. Several intraoperative strategies are available for dealing with a patient who has concomitant lung cancer and severe emphysema. The choice of technique depends on the location and size of the tumor, the severity and distribution of the emphysema, and the surgeon's experience and preference. Lung volume reduction surgery in well-selected patients who have severe emphysema results in postoperative improvement of symptoms and measured pulmonary function. The combination of lung cancer resection with LVRS offers selected patients who have concomitant early lung cancer and severe emphysema the opportunity to undergo resection of their cancer with improvement rather than further reduction in their pulmonary function. By traditional criteria these patients would otherwise be considered unsuitable surgical candidates because of the limited pulmonary function.

Combined cardiac and lung volume reduction surgery.

Coronary artery disease is prevalent in patients who have severe emphysema and who are being considered for lung volume reduction surgery (LVRS). Significant valvular heart diseases may also coexist in these patients. Few thoracic surgeons have performed LVRS in patients who have severe cardiac diseases. Conversely, few cardiac surgeons have been willing to undertake major cardiac surgery in patients who have severe emphysema. This report reviews the evidence regarding combined cardiac surgery and LVRS to determine the optimal management strategy for patients who have severe emphysema and who are suitable for LVRS, but who also have coexisting significant cardiac diseases that are operable.

Airway bypass treatment of severe homogeneous emphysema: taking advantage of collateral ventilation.

Airway bypass is being investigated as a new form of minimally invasive therapy for the treatment of homogeneous emphysema. It is a bronchoscopic catheter-based procedure that creates transbronchial extra-anatomic passages at the bronchial segmental level. The passages are expanded, supported with the expectation that the patency is maintained by paclitaxel drug-eluting airway bypass stents. The concept of airway bypass has been demonstrated in two separate experimental studies. These studies have shown that airway bypass takes advantage of collateral ventilation present in homogeneous emphysema to allow trapped gas to escape and reduce hyperinflation. It improves lung mechanics, expiratory flow, and volume. Airway bypass stent placements have been shown to be feasible and safe in both animal and human studies. Paclitaxel-eluting airway bypass stents were found to prolong stent patency and were adopted for clinical studies. A study evaluating the early results of the clinical application of airway bypass with paclitaxel-eluting stents found that airway bypass procedures reduced hyperinflation and improved pulmonary function and dyspnea in selected subjects who have severe emphysema. The duration of benefit appeared to correlate with the degree of pretreatment hyperinflation. These preliminary clinical results supported further evaluation of the procedure and led to the EASE Trial. The EASE Trial is a prospective, multicenter, randomized, double-blind, sham-controlled study. The trial aims to evaluate the safety and effectiveness of the airway bypass to improve pulmonary function and reduce dyspnea in homogeneous emphysema subjects who have severe hyperinflation. The trial is presently ongoing worldwide, though enrollment was completed.

Management of concomitant congenital tracheo-oesophageal fistula and cancer of the oesophago-gastric junction in an adult.

Congenital tracheo-oesophageal fistula in the adult is rare, and there have only been 16 such reported cases in the English literature. The concomitant presence of a cancer of the oesophago-gastric junction however has not been previously reported, and presents a treatment dilemma as to whether a staged or simultaneous surgical treatment should be performed. We report such a case that was successfully treated by staged surgical therapy.

Delayed re-exploration for bleeding after coronary artery bypass surgery results in adverse outcomes.

OBJECTIVE: We aimed to identify the impact of re-exploration for bleeding after coronary artery bypass grafting (CABG) and the effect of time delay, re-exploration within 12h (<12h) versus 12h or later (>or=12h). METHODS: Analyses of prospective clinical data on 3220 consecutive patients who underwent CABG between 2003 and 2005 were performed. Pearson chi(2) tests, Fisher's exact tests, Student's t-tests, Mann-Whitney U tests, or univariate logistic regression analysis were used to assess the effects of pre-operative and operative characteristics on re-exploration, and the effects of re-exploration and time delay on adverse outcomes. Predictors of re-exploration and its effect on adverse outcomes were further evaluated using multiple logistic regression analysis. RESULTS: One hundred ninety-one patients (5.9%) underwent re-exploration for bleeding. Re-explored patients as a group in comparison to the non-re-explored group had increased postoperative blood loss, transfusion requirements, duration of mechanical ventilation, ICU stay, intra-aortic balloon pump (IABP) and haemofiltration support, and mortality (all p<0.001). One hundred fifty-seven (82%) of the 191 patients were re-explored <12h. The group of patients who were re-explored <12h in comparison to >or=12h group had shorter ICU stay (median 3 vs 8.5 days; p<0.001), less IABP support (22.3 vs 44.1%; p=0.009) and a lower mortality (7 vs 29.4%; p=0.001). There was no significant difference in blood loss or transfusion requirements between the two groups. The predicted EuroSCORE risks of the <12h group was 6.66% and the observed mortality was 7% (p=0.865). The observed mortality of 29.4% in the >or=12h group was significantly higher than the predicted EuroSCORE risks of 7.59% (p<0.001). CONCLUSIONS: Patients requiring re-exploration for bleeding are at higher risk of adverse outcomes and this risk is increased if time to re-exploration is prolonged for 12h or longer.

A surgeon's case volume of oesophagectomy for cancer strongly influences the operative mortality rate.

OBJECTIVE: To assess if individual case volume of oesophagectomy for cancer influences the risk of mortality and long-term survival. METHODS: Between January 1994 and December 2005, 195 resections for oesophageal cancer were performed by nine surgeons in a single institution. Operative mortality, defined as in hospital death, was compared between the high-volume and low-volume surgeons. Multivariate logistic regression was used to analyze the risk factors for death between the two groups, also in the presence of covariates. RESULTS: There were 140 males and 55 females with mean age of 63.4 (32-84). Two high-volume surgeons performed 61% (118) of the operations with a mean of 11 per year compared to 4 per year in the low-volume group. The patients in the two groups were matched for age (63 years vs 64; p=0.53), sex (67 vs 79% male; p=0.07). Ivor Lewis resections were performed more frequently by high-volume surgeons (95 vs 73%; p<0.001). The operative mortality rate was much lower when high case volume surgeons performed the procedure (4 vs 17%; p=0.001). The relative risk of death when low-volume surgeons performed the procedure was 4.59 (95% CI 1.57-13.46; p<0.001). In-hospital mortality was significantly associated with low-volume surgeon when controlling separately for age (OR 4.60; 95% CI 1.55, 13.60, p=0.006), tumor stage (OR 3.76; 95% CI 1.24, 11.45, p=0.02) and tumor type (OR 3.87; 95% CI 1.29, 11.60, p=0.016). Kaplan-Meier curves comparing the survival of high- and low-volume surgeons showed no statistical differences (Log rank p=0.48). CONCLUSIONS: Operative mortality rate for oesophagectomy for cancer is strongly influenced by case volume and was 4.6-fold higher when performed by surgeons with low case volume. Patients with oesophageal cancer in need of an oesophagectomy may benefit from referral to a high-volume thoracic surgeon.

Feasibility and safety of airway bypass stent placement and influence of topical mitomycin C on stent patency.

OBJECTIVE: Airway bypass via transbronchial fenestration has been shown to improve forced expiratory volume and flow in explanted human emphysematous lungs. The aim of this study was to evaluate the feasibility and safety of in vivo airway bypass stent placement by using a canine model and to assess the influence of topical mitomycin C on the prolongation of stent patency. METHODS: With dogs under general anesthesia, suitable segmental and subsegmental bronchial wall sites were selected by direct visualization with a flexible bronchoscope. Peribronchial blood vessel injury was avoided by using a Doppler probe. Transbronchial fenestration was formed with a 22-gauge transbronchial needle, and the passage was then dilated with a 2.5-mm angioplasty balloon. A balloon expandable stainless-steel stent (3 mm long x 3 mm wide) with a sleeve of silicone rubber covering was placed within the fenestration. Animals were bronchoscoped weekly to assess stent patency. Seventy stents were placed in 12 dogs. Thirty-five served as controls, and the other 35 received transbronchoscopic topical application of mitomycin C once weekly to evaluate the effect on the maintenance of stent patency. Mitomycin C stents were divided into 4 groups according to the number of treatments: group A, 1 treatment only; group B, 4 weeks; group C, 7 weeks; and group D, 9 weeks. Each once-weekly mitomycin C application consisted of 0.2 mL at a concentration of 1 mg/mL, delivered through a small polyethylene catheter. RESULTS: Four instances of minor and brief bleeding occurred during stent placement and resolved without incident. One pneumothorax occurred and was treated by chest tube placement, without any adverse sequelae. There was no mortality associated with stent placement. No delayed hemorrhage or pneumothorax occurred. All control stents were occluded at the 1-week follow-up. The median durations of stent patency for group A (n = 8), group B (n = 9), group C (n = 10), and group D (n = 8) were 3, 8, 13, and greater than 20 weeks, respectively. CONCLUSIONS: Airway bypass stent placement can be performed safely. In an animal model, most stents became occluded within 1 week, but topical mitomycin application resulted in significant prolongation of patency.

Repair of congenital heart lesions combined with lung transplantation for the treatment of severe pulmonary hypertension: a 13-year experience.

OBJECTIVE: In patients with severe pulmonary hypertension associated with congenital heart disease, we prefer to perform repair of the congenital heart disease and lung transplantation whenever feasible so as to augment the donor pool and avoid the cardiac complications associated with heart transplantation. We report our experience with repair of congenital heart disease and lung transplantation and compare the results with those of patients who underwent heart-lung transplantation during the same period. METHODS: The records of patients who had repair of congenital heart disease and lung transplantation (n = 35) and heart-lung transplantation (n = 16) between 1990 and 2003 were reviewed. RESULTS: The underlying congenital heart disease in the repair of congenital heart disease and lung transplantation group included transposition of great vessels (n = 2), atrioventricular canal defect (n = 2), ventricular septal defect (n = 9), pulmonary venous obstruction (n = 7), scimitar syndrome (n = 2), pulmonary arterial atresia or stenosis (n = 5), and others (n = 8). Thirteen of the patients undergoing repair of congenital heart disease and lung transplantation (37.1%) had the congenital heart disease repaired before lung transplantation; the remaining congenital heart disease repairs were performed concurrently with transplantation. Sixteen patients underwent heart-lung transplantation because of poor left ventricular function or single-ventricle anatomy. Freedoms from bronchiolitis obliterans at 1, 3, and 5 years were 72.9%, 54.7%, and 54.7% for the repair of congenital heart disease and lung transplantation group and 77.8%, 51.9%, and 38.9% for the heart-lung transplantation group, respectively. Survivals at 1, 3, and 5 years were 62.9%, 51.4%, and 51.4% for the repair of congenital heart disease and lung transplantation group and 66.5%, 66.5%, and 60% for the heart-lung transplantation group, respectively. CONCLUSION: Repair of congenital heart disease and lung transplantation is a feasible treatment option. Long-term outcome is determined by associated complications related to lung transplantation. Despite the complexity of combined congenital heart disease repair with lung transplantation and the resulting perioperative morbidity, the patients had similar outcomes to those of patients who underwent heart-lung transplantation.

Long-range diffusion of hyperpolarized 3He in explanted normal and emphysematous human lungs via magnetization tagging.

Long-range diffusivity of hyperpolarized 3He gas was measured from the decay rate of sinusoidally modulated longitudinal nuclear magnetization in three normal donor and nine severely emphysematous explanted human lungs. This (long-range) diffusivity, which we call Dsec, is measured over seconds and centimeters and is approximately 10 times smaller in healthy lungs (0.022 cm2/s) than the more traditionally measured Dmsec, which is measured over milliseconds and submillimeters. The increased restriction of Dsec reflects the complex, tortuous paths required to navigate long distances through the maze of branching peripheral airways. In emphysematous lungs, Dsec is substantially increased, with some regions showing nearly the unrestricted value of the self-diffusion coefficient (0.88 cm2/s for dilute 3He in air, a 40-fold increase). This suggests the presence of large collateral pathways opened by alveolar destruction that bypass the airways proper. This destruction was confirmed by comparison with histology in seven lungs and by removal of trapped gas via holes in the pleural surface in five lungs.

3He diffusion MRI of the lung.

RATIONALE AND OBJECTIVES: MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. RESULTS: We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. METHODS: Techniques for purging and imaging excised lungs are discussed.

Dynamic four-dimensional computed tomography for preoperative assessment of lung cancer invasion into adjacent structures†.

OBJECTIVES: The 320-slice computed tomography (CT) provides three-dimensional and dynamic imaging resulting in the ability to assess motion analysis between two adjacent structures (the fourth dimension). Differential movements between two adjacent structures would indicate that there is no fixation between the two structures. METHODS: Eight patients with non-small-cell lung cancers located adjacent to vital structures (e.g. the great vessels) (n = 4), mediastinum (n = 1) or chest wall (n = 3) where conventional CT was unable to exclude local invasion underwent dynamic four-dimensional (4D) CT assessment. In 3 patients, the lung tumour was abutting the chest wall and 1 patient had tumour abutting the mediastinum. The remaining patients included a patient with a large 14-cm left lower lobe cancer abutting the descending thoracic aorta who had previous pleurodesis; a patient with an apical right upper lobe 6-cm cancer with static imaging appearances suggestive of tumour invasion into the apex, the mediastinal surface and superior vena cava (SVC); a patient with a 3.5-cm cancer which had a broad 2.5-cm base abutting the distal aortic arch and a patient with a 14-cm left upper lobe cancer abutting the aortic arch, descending thoracic aorta and chest wall. Differential movements between the tumour and adjacent structure on 4D CT were considered indicative of the absence of frank invasion. RESULTS: Dynamic 4D imaging revealed differential movements between the tumour and the adjacent structures in 7 cases, suggesting the absence of overt malignant invasion. Intraoperative assessments confirmed the findings. In 1 case, a small area of fixation seen on dynamic CT corresponded intraoperatively to superficial invasion of the adventitia of the SVC. CONCLUSIONS: Dynamic 4D 320-slice CT is useful in the preoperative assessment of the direct invasion of lung cancer into adjacent structures and hence its resectability.

Lung cancer resection combined with lung volume reduction in patients with severe emphysema.

OBJECTIVE: Certain patients with resectable lung cancer and severe respiratory limitation due to emphysema may have a suitable operative risk by combining cancer resection with lung volume reduction surgery. The purpose of this study is to review our experience with such patients. METHODS: A review was conducted on 21 patients with lung cancer in the setting of severe emphysema who underwent an operation designed to provide complete cancer resection and volume reduction effect. RESULTS: In the 21 patients, the mean preoperative forced expiratory volume in 1 second was 0.7 +/- 0.2 L (29% predicted), residual volume was 5.5 +/- 1.0 L (271%), and diffusing capacity for carbon monoxide was 8.0 +/- 2.2 mL/min/mm Hg (34% predicted). In 9 patients, the cancer was located in a severely emphysematous lobe and the lung volume reduction surgery component of the procedure was accomplished with lobectomy alone. In the remaining 12 patients, the cancer resection lobectomy (n = 9) and wedge resection (n = 3) were supplemented with lung volume reduction surgery. Final pathologic staging was stage I in 16 patients, stage II in 2 patients, and stage III in 2 patients. One patient was found to have stage IV disease due to multifocal tumors in separate lobes. There were no hospital deaths. Postoperative complications included prolonged air leak in 11 patients, atrial fibrillation in 6 patients, and reintubation for ventilatory assistance in 2 patients. All patients showed improved lung function postoperatively. Survival was 100% and 62.7% at 1 and 5 years, respectively. CONCLUSIONS: Patients with severe emphysema and resectable lung cancer who have a favorable anatomy for lung volume reduction surgery may undergo a combined cancer resection and lung volume reduction surgery with an acceptable risk and good long-term survival.

Benign esophageal tumors: introduction, incidence, classification, and clinical features.

Benign esophageal tumors comprise a diverse group of disorders that are rare in relation to malignant tumors or other benign conditions. The current article summarizes the literature with regard to the incidence and prevalence of benign tumors of the esophagus and discusses the various methods used to categorize these conditions. Summaries of important clinical features are provided for leiomyomas, esophageal cysts, fibrovascular polyps, papillomas, granular cell tumors and others.

Quality of life after lung transplantation.

Despite the potential differences in patient characteristics, study designs, and types of instruments used, this review of the literature showed several common findings. Important improvements in QOL are reported after lung transplantation. These improvements were observed when cross-sectional comparisons were made across the cohort of candidates and recipients and during longitudinal follow-up of patients at pretransplant and posttransplant time points. The improvements in QOL after transplantation seem to be sustained for at least 1 to 3 years after transplant. Lung transplant recipients generally were satisfied with their decision to have undergone transplantation. Many issues require further clarification. Variables that may influence QOL before and after lung transplantation, such as age, sex, pretransplant diagnosis, and type of procedure performed, should be considered carefully as study variables. Carefully designed, prospective longitudinal studies with many patients would result in stronger conclusions regarding the importance of QOL assessment in lung transplantation. It would be useful for a few QOL measurement tools to emerge as standard instruments so that many centers and investigators could adopt them to use independently. Standard instruments would allow comparison of outcomes between centers and would allow meta-analyses of multiple studies using the same methodology. Interpretation of the studies would be improved because there would be improved familiarity with a few tools, rather than vague recognition of a large variety of tools.