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Eighteen patients with esophageal carcinoma (16 adenocarcinoma, two squamous cell carcinoma) were treated with two cycles of induction chemotherapy consisting of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 (3-hour infusion), cisplatin 20 mg/m2/d x 4 days, and 5-fluorouracil 1 g/m2/d (continuous infusion x 4 days) separated by a 28-day interval before surgical resection. After resection, patients received two more cycles of the same regimen. A thorough staging evaluation was performed before patients were enrolled in the study. The salient chemotherapy toxicities included grade 3 nausea (two patients), grade 3 vomiting (two patients), grades 3 and 4 diarrhea (one patient each), and grades 3 and 4 neutropenia (two and 10 patients, respectively). No deaths occurred due to toxicity. Surgical resection was attempted in all 18 patients (100%) after two cycles of induction chemotherapy. Esophageal resection was successfully completed in 17 patients. Liver metastases were noted at laparotomy in the one patient who subsequently did not undergo esophageal resection. Surgical complications were minor, and no postoperative deaths occurred. Fifteen patients received two additional cycles of the paclitaxel/5-fluorouracil/cisplatin regimen postoperatively, two received only one cycle, and one refused further therapy. Of 15 patients alive, 14 show no evidence of disease. The 1-year actuarial survival rate of this group of patients is 82%. In conclusion, the paclitaxel/5-fluorouracil/cisplatin combination is well tolerated and is an active regimen in esophageal carcinoma.

Background: The purpose of this study was to conduct a pilot investigation of the cost-utility of lung transplantation. With this study we provide a threshold analysis to estimate the survival gains that must be achieved for lung transplantation to be considered a beneficial use of society's resources., Methods: A cross-sectional cohort design was used. All patients having undergone lung transplantation at the University of Pittsburgh Medical Center between March 1 and August 31, 1994, were identified via roster of transplant recipients (n = 20). Surviving patients were interviewed, by telephone, at their 1-year anniversary date. Utility was assessed by use of the quality of well-being scale. Direct cost of care was estimated from adjusted charges for the surgical admission, plus physician fees per the Medicare Physician Fee Schedule., Results: The mean quality of well-being score for this group was 0.54 +/- 0.198 SD (median = 0.599, range 0 to 0.728). Summing the physician cost and the adjusted charges for the inpatient operative admission, the average cost of lung transplantation was $153,921 +/- $133,981 SD (median $94,324, range $63,405 to $598,482). At a cost of $94,324 and a utility of 0.599, the survival gain from surgery must be 2.7 years for the cost of the procedure to be justified from a societal perspective., Conclusions: Because of the many limitations in this pilot study, no firm policy implication may be drawn from these data. Directions for future research are discussed.

Background: In patients with cystic fibrosis (CF) who are awaiting lung transplant, prolonged exposure to systemic antibiotics has frequently led to airway colonization with resistant isolates of Pseudomonas. This resistance limits the arsenal of effective antimicrobials available for infections after the initiation of immunosuppression and has been considered a theoretical deterrent to lung transplantation., Methods: Twenty CF transplant candidates with "pan-resistant" Pseudomonas received maintenance antibiotic therapy with aerosolized colistin sodium (75 mg b.i.d.), and intravenous antibiotics were eliminated. Ten other CF candidates did not use colistin sodium. Sputum cultures and antibiotic sensitivities were followed every 3-6 weeks., Results: All 20 candidates (100%) who used aerosolized colistin sodium became colonized with sensitive isolates of Pseudomonas in an average of 45.1+/-20.2 days. In contrast, only 3 of 10 CF transplant candidates (30%) who did not use colistin sodium later became colonized with sensitive isolates. The mean time to spontaneous emergence of sensitive organisms was 144.6+/-48.0 days in candidates who did not use colistin sodium and was significantly longer than in the candidates who used colistin sodium (P=0.007). The occurrence of redeveloping sensitive isolates of Pseudomonas was significantly greater in the candidates who used colistin sodium (P<0.05). Of the candidates who used colistin sodium, six have been transplanted at our institution. In five of these six recipients (83.3%) bacterial cultures taken from the explanted lungs continued to demonstrate sensitive organisms., Conclusion: Aerosolized colistin sodium may be a useful therapy to promote emergence of sensitive microbes in CF candidates with pan-resistant isolates of Pseudomonas.

Background: Conventional noninvasive staging of esophageal cancer is inaccurate. This study investigated the role of positron emission tomography (PET) in staging esophageal cancer., Methods: Patients with potentially resectable esophageal cancer were included. A whole-body PET scan was acquired after injection of 18F-fluorodeoxyglucose and was evaluated for areas of increased focal uptake. Accuracy was determined by comparing PET with surgical staging., Results: Potentially resectable esophageal cancer was identified in 35 patients. Positron emission tomography detected nine sites of distant metastases missed by conventional scanning, but one false-negative PET scan occurred in a patient with a 2-mm liver lesion. There were 11 false-negative PET scans for small, intracapsular local-regional nodal metastases (mean diameter 5.2 mm; range 2 to 10 mm). For distant metastases, the sensitivity was 88%, the specificity was 93%, and the accuracy was 91%. For local-regional nodal metastases, the sensitivity was 45%, the specificity was 100%, and the accuracy was 48%., Conclusions: Positron emission tomography improved our ability to detect distant metastases missed by conventional noninvasive staging of esophageal cancer. Small local-regional nodal metastases are not identified by current PET technology. Early use of PET in the staging of patients with esophageal cancer could facilitate treatment planning and identifying unsuspected distant metastases in up to 20% of patients with a negative metastatic survey by conventional staging.

Background: We have developed a safe, simple, and easily performed standardized exercise oximetry outpatient test to assess patients undergoing lung resections. We studied its ability to predict outcome after pneumonectomy in 46 consecutive patients over a 5-year period., Methods: Room air oximetry is initially performed at rest. The patient then begins to exercise on a stair-stepper apparatus (Stamina Stepper), which provides uniform resistance to stepping. Oxygen saturation values are noted at 10, 20, and 30 steps, equivalent to climbing three flights of stairs. Group 1 consisted of the patients who either had a resting saturation less than 90%, or desaturation greater than or equal to 4% during exercise. Group 2 consisted of all patients who had a preoperative forced expiratory volume in 1 second of 60% or less. Group 3 consisted of all patients who had a predicted postoperative forced expiratory volume in 1 second of 40% or less. Group 4 consisted of patients who had a predicted postoperative diffusing capacity of 40% or less., Results: There were four deaths (8.6%), 12 patients (26%) remained in the intensive care unit 4 or more days, and 11 patients (23%) suffered major morbidity. Desaturation during exercise (group 1) significantly predicted longer intensive care unit stay (p = 0.0002) and incidence of major morbidity (p < 0.0001). Groups 2, 3, and 4 were not significantly predictive of either longer intensive care unit stay or major morbidity., Conclusions: Standardized exercise oximetry performed in the outpatient facility is highly predictive of major morbidity and prolonged intensive care unit stay after pneumonectomy.

Background: The early postoperative course of single-lung transplant recipients depends on the recipient's underlying lung pathophysiology and the degree of ischemic-reperfusion injury. We examined the effect of pulmonary hemodynamics and preoperative diagnosis on early allograft function and the effects of pulmonary hemodynamics, allograft blood flow, and chest radiographs on length of mechanical ventilation and intensive care unit length of stay., Methods: We retrospectively collected data on 30 single-lung transplant recipients, 15 each with pretransplantation pulmonary hypertension and emphysema. Blood flow to the allografts was quantitated by perfusion scans obtained on the first postoperative day. Chest radiographs were graded for reperfusion injury. Pulmonary and hemodynamic data, gas exchange parameters, duration of mechanical ventilation, and intensive care unit stay were recorded., Results: Patients with pulmonary hypertension had a prolonged intensive care unit stay compared with emphysema patients, but pulmonary artery pressures were not quantitatively related to duration of ventilation during the intensive care unit stay. There was no difference in the severity of allograft infiltrate between the emphysema and pulmonary hypertensive patients. The day 1 chest radiograph score was highly predictive of an intensive care unit stay of > or = 7 days, although the threshold score of those with pulmonary hypertension was significantly lower than in emphysema patients. Allograft blood flow and pulmonary hypertension were not contributors to early graft dysfunction. Allograft perfusion decreased with increasing radiographically demonstrated infiltrate in those with emphysema but not in those with pulmonary hypertension., Conclusions: Elevated allograft blood flow and pressures do not exacerbate radiographically confirmed reperfusion injury. Reperfusion injury is the major cause of early respiratory morbidity after single-lung transplantation. Allograft perfusion in emphysema patients decreases in response to reperfusion injury, but pulmonary hypertension patients remain almost entirely dependent on allograft function, even with severe chest radiograph scores. This may be an important mechanism by which single-lung transplant recipients with emphysema, unlike those with pulmonary hypertension, are able to mitigate the degree of respiratory impairment associated with reperfusion injury.

Background: The role of nonanatomic wedge resection in the management of stage I (T1 N0 M0) non-small-cell lung cancer continues to be debated against the present gold standard of care--anatomic lobectomy., Methods: We analyzed the results of 219 consecutive patients with pathologic stage I (T1 N0 M0) non-small-cell lung cancer who underwent open wedge resection (n = 42), video-assisted wedge resection (n = 60), and lobectomy (n = 117) to assess morbidity, recurrence, and survival differences between these approaches., Results: There were no differences among the three groups with regard to histologic tumor type. Analysis demonstrated the wedge resection groups to be significantly older and to have reduced pulmonary function despite a higher incidence of treatment for chronic obstructive pulmonary disease when compared with patients having lobectomy. The mean hospital stay was significantly less in the wedge resection groups. There were no operative deaths among patients having wedge resection; however, a 3% operative mortality occurred among patients having lobectomy (p = 0.20). Kaplan-Meier survival curves were nearly identical at 1 year (open wedge resection, 94%; video-assisted wedge resection, 95%; lobectomy, 91%). At 5 years survival was 58% for patients having open wedge resection, 65% for those having video-assisted wedge resection, and 70% for those having lobectomy. Log rank testing demonstrated significant differences between the survival curves during the 5-year period of study (p = 0.02). This difference was a result of a significantly greater non-cancer-related death rate by 5 years among patients having wedge resection (38% vs 18% for those having lobectomy; p = 0.014)., Conclusion: Wedge resection, done by open thoracotomy or video-assisted techniques, appears to be a viable "compromise" surgical treatment of stage I (T1 N0 M0) non-small-cell lung cancer for patients with cardiopulmonary physiologic impairment. Because of the increased risk for local recurrence, anatomic lobectomy remains the surgical treatment of choice for patients with stage I non-small-cell lung cancer who have adequate physiologic reserve.

Background: Panel-reactive antibody (PRA) is commonly used before thoracic organ transplantation to estimate a potential recipient's degree of humoral sensitization., Methods: To assess the influence of an elevated PRA on survival and the incidence of rejection in pulmonary transplantation, the records of 247 patients that underwent single or double lung transplantation were reviewed., Results: Twenty-one of 247 patients (8.5%) had PRA values greater than 10%. Survival of this population was not significantly different from that of patients with low PRA levels: 74% (low PRA) vs 65% (elevated PRA) at 1 year and 58% in both groups at 3 years. The acute rejection rates (episodes/first 100 days) for the elevated and low PRA groups were 2.1 and 1.9, respectively (p = NS). Obliterative bronchiolitis developed in 38.9% of the high and 31.2% of the low PRA groups (p = NS). Six of 247 patients had a retrospective positive lymphocytotoxic cross-match result; three had PRA values greater than 10%. Patients with a positive cross-match result experienced similar survival and incidence of rejection as the remainder of the population. Among 957 patients evaluated for lung transplantation, 16 (1.7%) had a PRA (with dithiothreitol) greater than 15%. All had a history of pregnancy, blood transfusion, connective tissue disease, or previous transplantation., Conclusions: Humoral sensitization is uncommon in the lung transplantation population. A modestly elevated PRA does not predict survival or the development of acute rejection or bronchiolitis obliterans. PRA testing before lung transplantation should be reserved for those patients with specific risk factors for humoral sensitization.

Lung transplant recipients who have persistent acute cellular rejection are at increased risk for the development of chronic rejection, the leading cause of reduced long-term survival. This study evaluated the use of aerosolized cyclosporine as rescue therapy for unremitting acute rejection. Between June 1993 and March 1996, 18 patients with rejection that failed to resolve after therapy with pulse steroids and antilymphocyte globulin were enrolled in the study. Aerosolized cyclosporine A (300 mg) treatment was initiated for 10 consecutive days followed by a maintenance regimen of 3 days per week. Efficacy was assessed by graft histologic and pulmonary function testing. With the use of linear regression, results in these patients were compared with those in 23 control patients, matched for histologic acute rejection, who had continued to receive conventional rescue therapy. Two patients were unable to tolerate the treatments and were withdrawn from the study. Significant improvement in histologic rejection occurred in 14 of the remaining 16 patients after a mean of 37 days of aerosolized cyclosporine therapy. Measures of forced vital capacity and forced expiratory volume in 1 second (change in percent predicted/100 days plus or minus the standard error) increased over time in the treated patients whereas the condition of control patients declined despite repeated attempts at conventional rescue (forced vital capacity, aerosolized cyclosporine group, 4.6 +/- 2.9 vs control group -8.1 +/- 1.9, p = 0.001; forced expiratory volume in 1 second, aerosolized cyclosporine group, 2.1 +/- 4.4 vs control group -9.8 +/- 2.6, p = 0.043). Renal and hepatic toxicity during cyclosporine therapy was not observed. The incidence of acute histologic rejection (> or = A2) decreased from 2.49 +/- 0.68 episodes/100 days before aerosolized cyclosporine therapy to 0.72 +/- 0.3 episodes/100 days (p < 0.05). In summary, aerosolized cyclosporine is a safe and effective therapy for acute rejection that has failed to improve with conventional treatment.

The signal-recognition particle (SRP) and its receptor (SR) function in the co-translational targeting of nascent protein-ribosome complexes to the membrane translocation apparatus. The SRP protein subunit (termed Ffh in bacteria) that recognizes the signal sequence of nascent polypeptides is a GTPase, as is the SR-alpha subunit (termed FtsY). Ffh and FtsY interact directly, each stimulating the GTP hydrolysis activity of the other. The sequence of Ffh suggests three domains: an amino-terminal N domain of unknown function, a central GTPase G domain, and a methionine-rich M domain that binds both SRP RNA and signal peptides. Sequence conservation suggests that structurally similar N and G domains are present in FtsY. Here we report the structure of the nucleotide-free form of the NG fragment of Ffh. Consistent with a role for apo Ffh in protein targeting, the side chains of the empty active-site pocket form a tight network of interactions which may stabilize the nucleotide-free protein. The structural relationship between the two domains suggests that the N domain senses or controls the nucleotide occupancy of the GTPase domain. A structural subdomain unique to these evolutionarily conserved GTPases constitutes them as a distinct subfamily in the GTPase superfamily.

The application of lung transplantation as a treatment modality for patients with severe pulmonary disease has changed dramatically since its inception. At the University of Pittsburgh, the criteria for recipient selection continues to evolve and, in an effort to maximize scarce donor organs, the criteria for donor lung acceptance have been extended. Patient survival during the first 3 years after transplantation continues to improve but longer term survival is limited by infectious complications and chronic rejection. In early studies, the utilization of cyclosporine delivered directly to the lungs via aerosol has resulted in dramatic improvement in pulmonary function in recipients with immune mediated allograft injury and has allowed a reduction in systemic immunosuppression. We are hopeful that interventions such as this will result in prolongation of patient survival with less toxicity.

Mammalian signal recognition particle (SRP) and its homologues exhibit a phylogenetically conserved RNA domain, whose predicted secondary structure exhibits a hairpin motif with two bulged regions. Two RNA fragments comprising one (24 nt) or two (43 nt) of the conserved bulges were studied. Each fragment binds specifically to the domain of the Escherichia coli homologue of the SRP54 protein, which is involved in signal sequence recognition. The SRP RNA fragments exhibited a pronounced structural stabilization in the presence of Mg2+. Assignments of all base, H1', H2', and most imino proton resonances in the presence of Mg2+ were obtained for the 24mer RNA via NOE spectroscopy and correlated homonuclear NMR methods. 2D NOE patterns permitted a coarse structural description, revealing a relatively compact A-type geometry for the 24mer without any indications of looped-out nucleotides, syn-oriented bases, or base triplets. The GGAA-loop is structurally very similar to that of the GCAA tetraloop [Heus HA, Pardi A, 1991, Science 253:191-194]. Mg2+ seems to stabilize the structure of the conserved bulged region, which involves G:A and C:A mismatch pairs. Deviations from ideal A-type helicity are found for a larger region than the predicted secondary structure implies. Although no explicit assignment effort has been dedicated to the 43mer yet, striking similarity in chemical shift changes upon addition of Mg2+ allowed some structural conclusions. The bulge present in both RNA fragments exhibits a similar, pronounced flexibility in the absence of Mg2+, indicating that the additional bulge in the 43mer does not stabilize the other bulge.

Aortoesophageal fistula is a rare complication after thoracic aortic aneurysm repair. Six previously reported cases of aortoesophageal fistula management have been uniformly fatal. We present our successful management and review the literature of this topic.

Introduction: Opinions differ regarding differences between totally muscle-sparing thoracotomy and standard lateral thoracotomy approaches to pulmonary resection with respect to operative time, postoperative pain and morbidity, and occurrence of chronic postthoracotomy pain syndromes and subjective shoulder dysfunction., Methods: Three hundred thirty-five consecutive patients undergoing muscle-sparing thoracotomy (n = 148) or lateral thoracotomy (n = 187) to accomplish lobectomy for stage I lung cancer during a 40-month period were evaluated. Local rib resection was not employed, and two chest tubes were routinely used after operation in both thoracotomy groups. Epidural analgesia use was similar after operation in the two groups (muscle-sparing thoracotomy 38%, lateral thoracotomy 38%). The postoperative hospital courses and patient functional statuses at 1 year were examined., Results: Demographic analyses demonstrated no differences between groups in age, sex, or association of significant comorbid medical illness. Although the operative time required for muscle-sparing thoracotomy was shorter, there were no differences between thoracotomy approaches in any of the other primary acute postoperative variables analyzed (chest tube duration, length of hospital stay, postoperative narcotic requirements, and postoperative mortality). The frequencies of chronic pain and shoulder dysfunction assessed 1 year after operation were also similar between thoracotomy groups., Conclusions: The relative efficacies and rates of occurrence of acute or chronic morbidity are equivalent after muscle-sparing thoracotomy and standard lateral thoracotomy. Although muscle-sparing thoracotomy may possibly be performed more expediently, it appears that the singular advantage of muscle-sparing thoracotomy over standard lateral thoracotomy involves the preservation of chest wall musculature in case rotational muscle flaps should be needed later.

The use of bronchial blocker to optimize gas exchange in a patient with marked differential lung disease is reported. This technique proved to be a useful alternative in an ICU setting to independent lung ventilation.

Study Objective: The aim was to identify potential predictors of ICU length of stay (LOS) for single lung transplant patients., Design: Retrospective chart review., Setting: University medical center., Patients: All single lung transplant recipients for 1992 and 1993 at our institution., Results: Data were collected from 69 patients. The median ICU LOS was 5 days, and this was highly correlated with the duration of mechanical ventilation. The mean acute physiology and chronic health evaluation (APACHE II) score was 10. Patients with pulmonary hypertension had the longest ICU LOS. Similarly, patients with a measured transpulmonary gradient of 20 mm Hg or less had a significantly shorter ICU LOS. Patients with an immediate postoperative PaO2/fraction of inspired oxygen (FIo2) ratio greater than 200 mm Hg and a flow mismatch between the two lungs of 30% or less also had a significantly shorter ICU LOS. Positive and negative predictive values for the immediate postoperative PaO2/FIo2 ratio of 200 mm Hg or less were 77% for an ICU LOS greater than 5 days, and the calculated receiver operating characteristic (ROC) curve area was 0.74., Conclusion: Overall, the immediate postoperative PaO2/FIo2 ratio of 200 mm Hg or less had the best positive and negative predictive values as well as the highest ROC curve area for predicting an ICU LOS greater than 5 days.

Background: Transplantation of lung allografts from the same donor into 2 recipients ("twinning") provides an opportunity to study recipient and donor factors that influence early allograft function., Methods: Twenty-seven pairs of recipients were identified and evaluated using multivariate logistic regression analysis (p < 0.05). Four measures of early graft function were analyzed: alveolar-arterial gradient in the operating room, first alveolar-arterial gradient in the intensive care unit, alveolar-arterial gradient at 24 hours, and days of mechanical ventilation., Results: Analysis of the pooled data without regard to pairing showed that alveolar-arterial gradient in the operating room was influenced by donor age, length of donor hospitalization, recipient mean pulmonary artery (PA) pressure at unclamping, and transplantation of a left lung. The alveolar-arterial gradient in the intensive care unit was correlated with donor age, donor cause of death, and mean PA pressure on arrival in that unit. Only mean PA pressure remained significant at 24 hours. Days of mechanical ventilation was determined by mean PA pressure on arrival in the intensive care unit, drop in mean PA pressure during operation, and diagnosis of the recipient. In the paired analysis, receiving a left lung, recipient diagnosis (pulmonary hypertension worse than others), and need of cardiopulmonary bypass were significantly associated with immediate graft dysfunction, although these influences did not persist beyond the immediate postoperative period. Donor arterial oxygen tension and time of ischemia were not significant predictors in any analysis., Conclusions: Immediate allograft function was associated with donor-related characteristics initially, but these lost importance over the ensuing 24 hours. Recipient PA pressure was an immediate and persisting influence. In the analysis of differences in function between the members of each pair, transplantation of the left lung, recipient diagnosis, and cardiopulmonary bypass were identified, but their influence did not persist beyond the first 6 hours.

A 66-year-old woman presented with a bronchoesophagopleural fistula 10 weeks after thoracic photodynamic therapy for malignant mesothelioma. This is the third reported case of an esophagopleural fistula developing subsequent to photodynamic therapy for mesothelioma. We review the literature on this topic and report our successful management of this complication.

In the 1960s the promise of the Brantigan lung reduction surgery was shattered when it was shown that the improvement in airway conductance drifted back towards the preoperative value over a period of 12 to 18 months. Since then there has been a marked improvement in our understanding of emphysema, its pathology, and techniques for obtaining images of the lung. In addition, reliable automated cardiopulmonary and physiologic testing, advances in critical care medicine, and new pharmacologic agents have improved patient care. Surgical techniques now allow better control of air leaks and access to anatomic regions not previously accessible. The combination of all of the above makes lung reduction surgery worth re-examining as a palliative procedure for severely symptomatic patients. Clearly, it is not a panacea but can in some cases produce dramatic improvements in symptomatology and quality of life. This article presents the available data describing potential mechanisms of improvement and clinical outcomes following lung reduction surgery. It also outlines areas that need further work, such as patient selection and surgical techniques.

Background: Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema. The basic mechanisms responsible for the improvement, however, are not known., Methods: We studied 20 patients with diffuse emphysema before and at least three months after either a unilateral or a bilateral lung-reduction procedure. Clinical benefit was assessed by measurement of the six-minute walking distance and the transitional-dyspnea index, which is a subjective rating of the change from base line in functional impairment and the threshold for effort- and task- dependent dyspnea. Pressure-volume relations in the lungs were measured with static expiratory esophageal-balloon techniques, and right ventricular systolic function was assessed by echocardiography., Results: The patients had significant improvement in the transitional-dyspnea index after surgery (P<0.001). The mean (+/-SD) coefficient of retraction, an indicator of elastic recoil of the lung, improved (from 1.3+/-0.6 cm of water per liter before surgery to 1.8+/-0.8 after, P<0.001). Sixteen patients with increased elastic recoil had a greater increase in the distance walked in six minutes than the other four patients, in whom recoil did not increase (P=0.02). The improved lung recoil led to disproportionate decreases in residual volume as compared with total lung capacity (16 percent vs. 6 percent), but the decreases in both values were significant (P<0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P<0.001). End-expiratory esophageal pressure also decreased (P=0.002). These improvements in lung mechanics led to a decrease in arterial partial pressure of carbon dioxide form 42+/-6 to 38+/-5 mm Hg (P=0.006). Furthermore, the fractional change in right ventricular area, an indicator of systolic function, increased from 0.33+/-0.11 to 0.38+/-0.010 (P=0.02)., Conclusions: Lung-reduction surgery can produce increases in the elastic recoil of the lung in patients with diffuse emphysema, leading to short-term improvement in dyspnea and exercise tolerance.

Background: Thoracic surgeons have historically played a significant role in surgical treatment of benign esophageal disorders. With the advent of video-assisted thoracic surgical techniques, chest surgeons have also become adept at minimally invasive procedures. Thus, it seems appropriate that thoracic surgeons participate in minimally invasive antireflux operations, such as laparoscopic Nissen fundoplication., Methods: From February 1993 to May 1995, 66 patients (32 male, 34 female) with a mean age of 45.5 years (range, 15 to 82 years) underwent a laparoscopic fundoplication. Gastroesophageal reflux disease was diagnosed on the basis of history and endoscopically documented esophagitis or abnormal esophageal pH testing or both. There were 45 type I, 3 type II, and 7 type III hiatal hernias. Eleven patients had gastroesophageal reflux disease with no hernia., Results: Conversion to laparotomy occurred in 6 patients (9%) due to bleeding in 2 patients, inability to expose the gastroesophageal junction in 3, and gastric laceration in 1 patient. All but 1 patient underwent a Nissen fundoplication performed over a 50F to 60F dilator. The remaining patient (type II hernia without gastroesophageal reflux disease) underwent a reduction, closure, and anterior gastropexy. There was no operative mortality. Immediate postoperative morbidity included moderate dysphagia in 7 patients (11%), ileus in 2 patients (3%), and deep venous thrombosis and atrial arrhythmia in 1 each (1.5%). Excluding 1 patient hospitalized for 42 days due to severe psychosis, the mean postoperative stay was 4.0 +/- 2.5 days (median, 3 days). Three patients (5%) required dilation for dysphagia, and 1 (1.5%) has noted recurrent reflux during follow-up (mean, 14.4 months; range, 6 to 30 months). A single patient has undergone reoperation for persistent dysphagia (1.5%)., Conclusions: A laparoscopic Nissen procedure is safe, effective treatment for refractory gastroesophageal reflux disease when performed by thoracic surgeons experienced in minimally invasive surgical procedures.

We evaluated the use of a lateral thoracoscopic approach for lung reduction surgery in patients with diffuse emphysema. Sixty-seven patients with a mean age of 61.9 years underwent operation. Operative side was determined by preoperative imaging. The procedures were laser ablation in 10 patients and stapler resection in 57 patients. Ten patients, including six of the 10 patients in the laser-only group had poor outcome (death or hospitalization longer than 30 days), leading us to abandon the laser technique. Of the remaining 57 patients undergoing primary stapled resection, duration of chest tube placement averaged 13 days (range 3 to 53 days) with a mean hospital stay of 17 days (range 6 to 99 days). Seven patients required ventilation for longer than 72 hours, six patients underwent conversion of the procedure to open thoracotomy, four patients acquired arrhythmias, and three patients were treated for empyema. There was one early death (1.7%), from cardiopulmonary failure. Forty patients returned for 3-month evaluation. Significant (p < 0.0001) improvements were seen in forced vital capacity (2.69 L after vs 2.26 L before) and forced expiration volume in 1 second (1.04 L after vs 0.82 L before), with 25 of 40 patients (63%) showing an improvement of more than 20%. Lung volume measures, in particular residual volume, fell significantly. Arterial blood gas analysis revealed that carbon dioxide tension fell significantly in patients with preoperative hypercapnia (carbon dioxide tension > 45 mm Hg, p = 0.018). Six-minute walk test results improved (894 feet after vs 784 feet before, p = 0.002), and symptomatic benefit was confirmed by significant improvement in the dyspnea index. The combination of both hypercapnia and reduced single-breath diffusing capacity for carbon monoxide was significantly more frequent (p = 0.0026) and was 86% specific (5 of 6 patients) in predicting serious postoperative risk. We conclude that the lateral thoracoscopic surgical approach to diffuse emphysema offers significant improvement in pulmonary mechanics and functional impairment. Patients with a combination of hypercapnia and reduced single-breath diffusing capacity for carbon monoxide should not be considered for this procedure because of significant perioperative risk.

Primary severe donor lung dysfunction (DLD) is a significant complication after lung transplantation (LTx), and a high mortality is reported with conventional therapy. The purpose of this report is to review the experience of the University of Pittsburgh with extracorporeal membrane oxygenation (ECMO) for primary severe DLD after LTx. From September 1991 to May 1995, 220 LTx were performed at our center. Eight patients (8/220 = 3.6%) with severe DLD after LTx required ECMO support. The age of LTx recipients was 44 +/- 5 years (mean +/- SD); seven patients were female and one was male. Indications for LTx were: chronic obstructive pulmonary disease in four patients, bronchiectasis in two, and pulmonary hypertension in two. There were three single LTx and five bilateral LTx. The interval from LTx to institution of ECMO was 5.6 +/- 3.2 h (range 0-10 h). Three patients were supported with veno-venous (v-v) ECMO and five had veno-arterial (v-a) ECMO. The duration of ECMO support was 7.3 +/- 4.8 days (range 3-15 days). activated glotting time (ACT) was maintained between 110 and 180 s with intermittent use of heparin. Seven patients (7/8 = 87%) were successfully weaned from ECMO and six patients (6/8 = 75%) were discharged home; they are currently alive after a follow-up of 17 +/- 10.1 months. One patient died on ECMO support for refractory DLD and another died 2 months after ECMO wean from multisystem organ failure. At 6 months follow-up, forced expiratory volume in 1 s (FEV1) is 2.35 +/- 0.91 (75% +/- 17.4% predicted) and mean forced vital capacity (FVC) is 2.53 +/- 0.81 (64% +/- 14% predicted). We conclude that ECMO can be lifesaving when instituted early after primary severe DLD. The v-v ECMO support is preferred when the patient is hemodynamically stable and adequate long-term function of the allograft is anticipated.

Video-assisted thoracic surgery (VATS) has assumed greater importance in the management of pleural disease. Since 1990, we have performed VATS procedures to manage a variety of pathologic pleural processes in 306 patients. The 99 patients with complex empyemas or hemothoraces are the focus of this report. Seventy-six patients with complex empyemas (including 26 chronic) were approached with VATS after inadequate chest tube drainage. The causes associated with the thoracic empyemas were parapneumonic collections in 47, after hemothorax in 8, infected sympathetic effusions associated with intra-abdominal sepsis in 6, postresectional in 5, prolonged bronchopleural fistula following spontaneous pneumothorax in 4, chronic drainage of malignant pleural effusions in 4, and chronic drainage of pleural effusion in 2 patients undergoing chemotherapy. Ages ranged from 14 to 78 years. Sixty-three patients (83%) were treated with thoracoscopic drainage +/- decortication alone. Thirteen patients (17%) required subsequent thoracotomy for decortication, including 12 of the 26 (46%) chronic empyemas known to be greater than 3 weeks old. Chest tubes were removed 3.3 +/- 2.9 days postoperatively in 67 patients; 9 patients (12%) were sent home with empyema tubes. Postoperative hospital stay for these patients with empyema averaged 7.4 +/- 7.2 days. There were five deaths, all related to progressive sepsis from associated pneumonia (6.6%). Twenty-three patients underwent thoracoscopic evacuation of hemothoraces that resulted following open heart surgery in 6, thoracic trauma in 7, were iatrogenic in 7, and bleeding into malignant effusions in 3. All were successfully treated by thoracoscopic drainage and pleural debridement alone. Chest tubes were removed 2.8 +/- 0.5 days postoperatively and hospital stay averaged 4.3 +/- 1.9 days. There were no complications; one patient with a hemothrax (after heart transplant) died of unrelated causes. In our experience, VATS has been highly successful in the early management of empyemas and hemothoraces. Conversion to open thoracotomy must always be anticipated, especially when approaching chronic empyemas.

Background: We and others have demonstrated that a low level of donor cell chimerism was present for years after transplantation in tissues and peripheral blood of heart and lung recipients; it was associated, in the latter, with a lower incidence of chronic rejection. To augment this phenomenon, we initiated a trial combining simultaneous infusion of donor bone marrow with heart or lung allotransplantation., Methods: Between September 1993 and January 1995, 15 nonconditioned patients received either heart (n = 10) or lung (n = 5) allografts concurrently with an infusion of unmodified donor bone marrow (3.0 x 10(8) cells/kg), and were maintained on immunosuppressive regimen consisting of tacrolimus and steroids., Results: There was no complication associated with the infusion of donor bone marrow. Chimerism was detectable in 73% of bone marrow-augmented patients up to the last sample tested. Of the 5 control recipients who did not receive bone marrow infusion, only 1 had detectable chimerism by flow on postoperative day 15, which dwindled to an undetectable level by postoperative day 36. None of the patients had evidence of donor-specific immune modulation by mixed lymphocyte reaction., Conclusions: The combined infusion of donor bone marrow and heart or lung transplantation, without preconditioning of the recipient, is safe and is associated with an augmentation of donor cell chimerism.

Background: The malignant potential of indeterminate solitary pulmonary nodules (SPN) mandates accurate diagnostic management., Methods: 613 patients undergoing either computed tomographic lung biopsy (CT-Bx) (n = 312) or thoracoscopic excisional biopsy (Thor-Bx) (n = 301) for the diagnosis of SPN were evaluated for relative accuracy, complications, and effect on clinical treatment., Results: CT-Bx identified a malignant diagnosis (Dx) in 201 (64%) of 312 patients; 85 (42%) underwent operations. A total of 116 patients (58%) with synchronous cancer (n = 16), impaired physiologic condition, or unresectable lesions (n = 100) were not operated. Surgical treatment was deferred for 20 patients (6%) with a "specific benign" Dx and 44 physiologically impaired patients with "nonspecific benign" CT-Bx. Forty-seven patients with "nonspecific benign" Dx underwent operation. Thirty-two (68%) lesions were malignant (4 metastatic, 28 primary cancer). CT-Bx accuracy was 86% for malignant and 79 (71%) of 111) for benign lesions. Surgery was still required for 132 (82%) of 163 patients with resectable lesions. Complications occurred in 24% of patients. A specific benign or malignant Dx was obtained in 292 (96%) of 301 patients undergoing Thor-Bx. Conversion to thoracotomy for lobectomy occurred in 38 (21%) of 179 patients with lung cancer. One hundred forty-one patients with lung cancer and impaired physiologic condition and all patients with metastatic (n = 44) and benign lesions (n = 78) had thoracoscopic resection alone. Complications occurred in 22% of patients., Conclusions: Limited accuracy for benign Dx with CT-Bx requires surgical biopsy for patients with SPN with adequate physiologic reserve. Thor-Bx is a safe and accurate minimally invasive surgical approach to resectable peripheral SPN.

Primary graft failure is a catastrophic event in lung transplantation. Failure is characterized by profound abnormalities of gas exchange that are frequently unresponsive to alterations in mechanical ventilation. This condition can be fatal and, if less severe, is usually associated with significant permanent damage to the allograft. We report the use of extracorporeal membrane oxygenation as a means to support lung transplant recipients with severe graft failure. Since 1991, extracorporeal membrane oxygenation has been used on 17 occasions for the temporary support of 16 adult lung transplant recipients. All patients met or exceeded standard National Institutes of Health guidelines for institution of extracorporeal membrane oxygenation. Nine double lung, six single lung, and one heart-lung recipients were supported for 1 to 12 days (mean 4.6 +/- 2.2 days). Extracorporeal membrane oxygenation was instituted early, within 7 days of transplantation, in ten patients. Eight early patients (80%) were successfully weaned from extracorporeal membrane oxygenation. Seven of ten (70%) patients were long-term survivors, and five of the seven had normal lung function. In comparison, there were no survivors among six recipients placed on extracorporeal membrane oxygenation for late (> or = 7 days) graft dysfunction. Extracorporeal membrane oxygenation is a lifesaving adjunct in recipients with acute graft failure after lung transplantation. Ischemia-reperfusion injury and acute graft dysfunction after lung transplantation can be successfully reversed with early aggressive intervention.

Background: A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary immunosuppressive agent after lung transplantation., Methods: Between October 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying disease., Results: One-year and 2-year survival rates were similar in the two groups, although the trend was toward increased survival with tacrolimus. Acute rejection episodes per 100 patient-days were fewer (p = 0.07) in the tacrolimus group (0.85) than in the cyclosporine group (1.09). Obliterative bronchiolitis developed in significantly fewer patients in the tacrolimus group (21.7%) compared with the cyclosporine group (38%) (p = 0.025), and there was greater freedom from obliterative bronchiolitis over time for patients receiving tacrolimus (p < 0.03). Significantly more cyclosporine-treated patients (n = 13) required crossover to tacrolimus than tacrolimus-treated patients to cyclosporine (n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acute rejection in 6 of 9 patients. The overall incidence of infections was similar in the two groups, although bacterial infections were more common with cyclosporine (p = 0.0375), whereas the risk of fungal infection was higher with tacrolimus (p < 0.05)., Conclusions: This trial demonstrates the advantage of tacrolimus in reducing the risk of obliterative bronchiolitis, the most important cause of long-term morbidity and mortality after lung transplantation.

Background: Refractory rejection is a major cause of morbidity and death among lung transplant recipients. Traditional rescue therapies have proved only modestly successful. We recently demonstrated the safety of inhaled cyclosporine for patients with end-stage chronic rejection; this trial was extended to patients with refractory acute rejection. The present study was to determine whether effective inhaled cyclosporine therapy was correlated with suppression of cytokine gene expression., Methods: Twelve lung transplant recipients were studied. Maintenance therapy, cyclosporine or FK 506, azathioprine, and prednisone, was continued, and inhaled cyclosporine at a dose of 300 mg/day was added. Pulmonary function testing and histologic characteristics from transbronchial biopsy specimens were used to assess efficacy of therapy. Bronchoalveolar lavage (BAL) and peripheral blood cells were analyzed for the presence of messenger RNA by using 32P-labeled primers of cytokines interleukin-2 (IL-2), IL-6, IL-10, and interferon-gamma (gamma) via reverse transcriptase-polymerase chain reaction., Results: Nine of 12 patients (five with acute rejection, four with chronic rejection) exhibited histologic resolution of rejection within 3 months of inhaled cyclosporine therapy. Pulmonary function (forced expiratory volume in 1 second) improved from pretherapy levels in the patients with acute rejection (p < 0.05). All of the nine histologic responders exhibited 4- to 150-fold decreases (p < 0.05) in IL-6 and interferon-gamma messenger RNA levels in the BAL, whereas the three patients who failed exhibited persistent or increased cytokine profiles. IL-2 and IL-10 in BAL and peripheral blood lymphocyte cytokines were not informative., Conclusions: These results indicate that inhaled cyclosporine is effective therapy for refractory pulmonary rejection and that its mechanism of action is associated with suppression of proinflammatory cytokines IL-6 and interferon-gamma within the allograft.

Since January 1991, we have performed 79 video-assisted neodymium: yttrium-aluminum-garnet laser resections for pulmonary nodular or interstitial disease. Pathologic examination demonstrated malignancy in 59 patients (32 primary and 27 metastatic), benign nodules in 11, interstitial processes in seven, and granulomatous disease in two. There were 39 men and 40 women with a mean age of 63.4 +/- 12.5 years. Thirty-nine patients underwent resection with the neodymium:yttrium-aluminum-garnet laser alone and 40 had lesions resected with a combination of laser and endoscopic stapling. Laser excision was performed for lesions deep in the substance of the lung or on its effaced surface; both are locations that make stapling alone difficult. Fifteen of 32 patients with a diagnosis of primary lung malignancy underwent open anatomic resections. Pulmonary reserves of the other 17 patients were inadequate for further resection. Operative time, duration of chest tube placement, length of hospital stay, and complication rate were compared with those for 72 patients undergoing video-assisted thoracic surgical resection of nodules with staplers alone. Although operative time for laser-assisted procedures was longer (p < 0.05), there were no differences in duration of chest tube placement or hospital stay compared with stapled resections. The complication rate for laser-treated cases was not higher than for stapled resections and consisted primarily of air leaks lasting 2 to 7 days. The neodymium:yttrium-aluminum-garnet laser is a safe and precise primary or adjunctive tool for video-assisted thoracic surgical pulmonary resection.

Transesophageal echocardiography identified malposition of an extracorporeal membrane oxygenation venous cannula across the interatrial septum into the left atrium and the presence of a clot within the cannula's lumen. Transesophageal echocardiography also guided the withdrawal of the cannula into the inferior vena cava.

Background and Methods: To determine the long-term functional outcome for single versus bilateral lung transplant for nonseptic obstructive lung disease, we compared the results from 39 single and nine bilateral lung transplant procedures. The nine bilateral lung transplants included three en bloc double lung and six bilateral sequential lung transplants., Results: Early deaths within 30 days of transplantation occurred in two of nine (22%) bilateral and 4 of 39 (10%) single lung transplants (p = Not significant). Compared with pretransplant values, pulmonary function as assessed by the spirometric indexes of the percent predicted forced vital capacity, forced expiratory volume in one second, forced expiratory volume in one second/forced vital capacity, and forced expiratory flow at 25% and 75% of forced vital capacity improved significantly up to at least 12 months after transplantation for both single and bilateral lung transplant recipients. The degree of pulmonary function improvement was better in single as compared with bilateral lung recipients. By 6 months after transplantation, all but one single and all bilateral lung recipients were in New York Heart Association class I or II (p = Not significant). One-year survival was significantly better after single (77%) compared with after bilateral lung transplantation (35%) (p < 0.05)., Conclusions: These results suggest that single lung transplantation is the procedure of choice for patients with nonseptic obstructive lung disease.

Since 1991, we have managed 57 patients with benign (10), malignant (23), or lung transplantation (24) airway obstructions using silicone stenting and debridement (manual/neodymium:yttrium-aluminum garnet laser). Ten patients with benign lesions (4 intubation, 4 inflammatory, 1 malacia, 1 bronchial fistula) had 4 T tubes, 3 Y stents, 3 bronchial stents, and 1 straight tracheal stent placed. Eight of 10 patients (80%) received symptomatic relief with the stents in place for up to 43 months. Twenty-three patients with malignant strictures (18 lung, 5 metastatic) had 26 stents inserted (13 Y stents, 12 bronchial, 1 T tube) of which 16 required combined debridement and stenting. Four stents required repositioning. three hospital deaths were due to unrelated causes. Of 20 discharged patients, 6 remain alive at 2 to 10 months, whereas 14 patients who died of progressive disease obtained effective palliation for 10.5 +/- 5.6 months. Significant bronchial anastomotic complications developed in 24 of 212 lung transplants (11.3%). Thirty-one stents were placed in 19 of the patients; 5 patients were managed with laser debridement alone. Of the 19 patients receiving stents, 3 required only temporary stents (6 to 15 days), 11 patients needed long-term stents (40 to 507 days), and 5 patients died with their stents in place functioning well. All patients received symptomatic relief with stenting. There were no procedure-related deaths and one bronchial laceration during attempted stent placement. Early, aggressive treatment of benign and malignant tracheobronchial strictures with endoscopic debridement and stenting is safe and well tolerated, and effectively palliates airway obstruction. Repositioning of stents frequently may be required in the transplant population.(ABSTRACT TRUNCATED AT 250 WORDS)

We present a case of bridging to lung transplantation by means of laser ablation of emphysematous bullae in a lung transplant candidate. The patient underwent successful left single-lung transplantation 17 months after lung reduction. He is now well 3 months after transplantation.

With current immunosuppressive regimens, rejection is common after lung transplantation. Acute rejection is usually easily reversible with therapy, but chronic rejection often responds poorly and is the leading cause of late morbidity and mortality. Although the pathogenesis of chronic rejection is not fully understood and might be different from ACR, the studies summarized in this review support the concept that alloimmune responses are of fundamental importance. Acute rejection and infection, particularly with CMV, appear to promote changes within the allograft that increase the risk of chronic rejection. Although the progression of OB in some patients might be arrested with immunosuppression, a large percentage of patients with OB suffer from a continuous loss of lung function. Improvement in the long-term outcome of lung transplant recipients will require both better immunosuppressive agent and more specific therapy such as induction of donor-specific tolerance.

Background: The efficacy and therapeutic impact of needle-localized thoracoscopic resection (NLTR) was examined in patients with cancer who present with small indeterminate pulmonary nodules (IPNs)., Methods: Between December 1991 and August 1992, 30 patients underwent needle localization of 33 IPNs under computed tomography (CT) guidance followed by thoracoscopic resection. All previous attempts to characterize these small pulmonary nodules (mean size 7.9 +/- 4.9 mm) had failed. Twenty patients had an established diagnosis of cancer 1 month to 20 years before detection of the lung abnormality, whereas the remaining patients had no prior history of cancer., Results: Histology of NLTR specimens in patients with a previous diagnosis of malignancy included 13 malignant and seven benign lesions. In all patients with cancer, therapeutic decisions were influenced by NLTR results. Thoracoscopic related complications were noted in two patients. Average length of hospital stay for NLTR was 6.7 +/- 3.9 days., Conclusion: NLTR in this series has proven to be a safe, well-tolerated, and accurate method for diagnosing and influencing the management of recently identified IPN. NLTR appears warranted for small pulmonary nodules not amenable to less invasive diagnostic modalities.

The indications for single, bilateral, and heart-lung transplantation for patients with pulmonary hypertension remain controversial. We retrospectively analyzed the results from 11 single, 22 bilateral, and 24 heart-lung transplant procedures performed between January 1989 and January 1993 on 57 consecutive patients with pulmonary hypertension caused by primary pulmonary hypertension (n = 27) or Eisenmenger's syndrome (n = 30). Candidates with a left ventricular ejection fraction less than 35%, coronary artery disease, or Eisenmenger's syndrome caused by surgically irreparable complex congenital heart disease received heart-lung transplantation. All other candidates received single or bilateral lung transplantation according to donor availability. Although postoperative pulmonary artery pressures decreased in all three allograft groups, those in single lung recipients remained significantly higher than those in bilateral and heart-lung recipients. The cardiac index improved significantly in only the bilateral and heart-lung transplant recipients. A significant ventilation/perfusion mismatch occurred in the single lung recipients as compared with bilateral and heart-lung recipients because of preferential blood flow to the allograft. Graft-related mortality was significantly higher and overall functional recovery as assessed by New York Heart Association functional class was significantly lower at 1 year in the single as compared with bilateral and heart-lung recipients. Thus bilateral lung transplantation may be a more satisfactory option for patients with pulmonary hypertension with simple congenital heart disease, absent coronary arterial disease, and preserved left ventricular function. Other candidates will still require heart-lung transplantation.

An intravenous membrane oxygenator is being developed to supplement oxygen and carbon dioxide exchange in patients with temporary and potentially reversible lung failure in either a lung transplantation setting or in cases of acute respiratory distress from multiple causes. Our device incorporates a pulsatile balloon that is centrally located and around which are mounted microporous hollow fibers. Oxygen is vaccuumed through the fibers with resultant gas exchange. The rhythmic pulsations of the balloon enhance cross-flow and three-dimensional convective mixing at the blood-fiber interface and thus promote more efficient oxygen-carbon dioxide exchange. Seven intravenous membrane oxygenator prototypes have been designed and fabricated. Modifications in design have led to a progressive improvement in gas flux. Gas exchange performance measured in vitro and with both saline solution and fresh ox blood have shown gas exchange as high as 203 ml/min/m2 for oxygen and 182 ml/min/m2 for carbon dioxide. In vivo dog experiments with the device positioned in the inferior vena cava and right atrium have shown over a 50% increase in oxygen flux with balloon activation versus the static situation without changes in hemodynamics. The size of the prototype tested in animals can be scaled up fivefold for anticipated human trials. Our results indicate that our intravenous membrane oxygenator prototypes now under development may be an alternative to extracorporeal membrane oxygenation in the treatment of temporary respiratory failure.

Single lung transplantation for pulmonary hypertension (PH) remains a controversial therapy. We retrospectively studied 48 consecutive recipients of single-lung allografts to determine if preoperative PH was associated with increased mortality or morbidity. Recipients were divided into two groups; those who did have preoperative PH, defined as mean pulmonary arterial pressure less than or equal to 30 mm Hg (n = 29; group 1), and those recipients with PH who had a mean pulmonary arterial pressure greater than 30 mm Hg (n = 19; group II). Mean pulmonary arterial pressure and pulmonary vascular resistance decreased significantly after transplantation in recipients with PH. These values remained significantly higher as compared with those in recipients without pretransplantation PH. Postoperative pulmonary ventilation/perfusion scans demonstrated significant ventilation/perfusion mismatch in lung allografts with pretransplantation PH (p < 0.05). The mean duration of intensive care unit stay was significantly longer in recipients with PH. Although operative mortality was similar between the groups, preoperative PH was associated with significantly lower 1-year survival (53% versus 72%; p < 0.05) and New York Heart Association functional class (p < 0.05). We conclude that preoperative PH in single-lung transplant recipients is associated with significantly increased mortality, prolonged intensive care unit stay, and less symptomatic improvement. Thus, despite a shortage of donor organs, single-lung transplantation may be suboptimal therapy in patients with PH. Further study comparing single versus bilateral lung transplantation for PH is necessary.

Present clinicopathologic staging of non-small cell lung cancer is limited in its ability to provide more than a general prognostic estimate in patients with lung cancer who have resectable disease. This study was performed to identify whether the ability to adapt tumor tissue from resectable (stage I to IIIa) non-small cell lung cancer was associated with a poorer prognosis and an increased risk for early tumor recurrence. We attempted to culture a tumor specimen obtained from 90 patients with resectable non-small cell lung cancer. We used a culture medium conditioned by exposure to the lung cancer cell line A549-1, a known producer of autocrine lung cancer growth factors, and provided tumor colony scaffolding using a feeder layer of inactivated fibroblasts, and found these measures improved tumor culture yields. Twenty-two cell lines were obtained, a success rate of 24.4%. Tumor recurrences were more common (79%) among the culture-positive patients than among the culture-negative patients (37.5%; p < 0.002). For all patients, survival at 19 months in the culture-positive patients was 50.0%, compared with 83.6% in the culture-negative patients (p < 0.005). The median survival for the culture-positive patients was 15 months, versus 21.7 months for the culture-negative patients (p < 0.004). The establishment of a culture was a predictor of shortened survival for patients with stage I disease. In patients with stage I disease, survival at 19 months was 54.5% for the culture-positive patients, versus 89% for the culture-negative patients (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical courses of two patients with moderate atherosclerotic aneurysmal dilation of the upper abdominal aorta suffering significant thrombo-embolic sequelae following transhiatal esophagectomy are presented. Inadvertent dislodgement of debris from the diseased aorta during the course of the hiatal and intrathoracic "blunt" dissection was felt to be responsible for this uncommon postoperative problem. This potential complication should be kept in mind when operating near the esophageal hiatus during the course of esophagectomy in such vasculopathic patients.

We report a nearly complete obstruction of the left mainstem bronchus by a fibrinomyxoid plaque about 12 h after laser resection of scar/granulation tissue at a left bronchial anastomosis 27 days after a left single lung transplant. The formation of this plaque was associated with respiratory failure. The plaque was removed by grasping the plaque with biopsy forceps inserted through a fiberoptic bronchoscopy that was placed into the left mainstem bronchus via an endotracheal tube while the patient was receiving manual ventilation under general anesthesia. The respiratory failure resolved with removal of the plaque. To our knowledge, this is a complication that has not been reported previously.

Providing adequate ventilation and unencumbered access for manipulation of the airway or esophagus during rigid endoscopic procedures can be problematic. We describe a method of nasotracheal high-frequency jet ventilation that is ideally suited for many patients requiring rigid upper endoscopy.

The prevalence and severity of chronic pain after video-assisted thoracic surgery for pulmonary resection remains to be defined. Three hundred forty-three of 391 consecutive patients 3 to 31 months after pulmonary resection by lateral thoracotomy (n = 165) or video-assisted thoracic surgery (n = 178) responded to a questionnaire aimed at comparing the relative occurrence of chronic postoperative pain after video-assisted thoracic surgery and lateral thoracotomy approaches for pulmonary resection. Patients less than 1 year after operation (video-assisted thoracic surgery = 142; thoracotomy = 97) and more than 1 year after operation (video-assisted thoracic surgery = 36; thoracotomy = 68) were analyzed as individual cohorts. Chronic pain was assessed by questioning patients about the presence and the intensity of discomfort on the side of the operation (using a visual analog scale) and their need for analgesic medication and the presence of ongoing limitations in shoulder function. Patients who underwent video-assisted thoracic surgery (less than 1 year from operation) had less pain and subjective shoulder dysfunction although their pain medication requirements were similar to those of thoracotomy patients less than 1 year from operation. After 1 year, there was no significant difference in these "pain related" morbidity parameters between the two surgical approach groups (video-assisted thoracic surgery or thoracotomy).

We have conducted a unique prospective randomized study to compare the effect of FK506 and cyclosporine (CsA) as the principal immunosuppressive agents after pulmonary transplantation. Between October 1991 and March 1993, 74 lung transplants (35 single lung transplants [SLT], 39 bilateral lung transplant [BLT]) were performed on 74 recipients who were randomly assigned to receive either FK or CsA. Thirty-eight recipients (19 SLT, 19 BLT) received FK and 36 recipients (16 SLT, 20 BLT) received CsA. Recipients receiving FK or CsA were similar in age, gender, preoperative New York Heart Association functional class, and underlying disease. Acute rejection (ACR) was assessed by clinical, radiographic, and histologic criteria. ACR was treated with methylprednisolone, 1 g i.v./day, for three days or rabbit antithymocyte globulin if steroid-resistant. During the first 30 days after transplant, one patient in the FK group died of cerebral edema, while two recipients treated with CsA died of bacterial pneumonia (1) and cardiac arrest (1) (P = NS). Although one-year survival was similar between the groups, the number of recipients free from ACR in the FK group was significantly higher as compared with the CsA group (P < 0.05). Bacterial and viral pneumonias were the major causes of late graft failure in both groups. The mean number of episodes of ACR/100 patient days was significantly fewer in the FK group (1.2) as compared with the CsA group (2.0) (P < 0.05). While only one recipient (1/36 = 3%) in the group treated with CsA remained free from ACR within 120 days of transplantation, 13% (5/38) of the group treated with FK remained free from ACR during this interval (P < 0.05). The prevalence of bacterial infection in the CsA group was 1.5 episodes/100 patient days and 0.6 episodes/100 patient days in the FK group. The prevalence of cytomegaloviral and fungal infection was similar in both groups. Although the presence of bacterial, fungal, and viral infections was similar in the two groups, ACR occurred less frequently in the FK-treated group as compared with the CsA-treated group in the early postoperative period (< 90 days). Early graft survival at 30 days was similar in the two groups, but intermediate graft survival at 6 months was better in the FK group as compared with the CsA group.

Although airway, arterial, and venous connections required for lung transplantation appear simple, in practice we have encountered morbid early stenosis and obstructions, which are now avoided by technical modifications gradually made since 1985 in 134 cases (60 single lung and 74 double lung). Our initial eight double lung transplant procedures were done with tracheal anastomoses and omental wraps, but ischemic disruption, with a 75% (6 of 8) rate of complications, resulted in the subsequent use of bi-bronchial connections. A total of 192 bronchial anastomoses were reviewed (60 single lung, 66 double lung). Although all anastomoses were constructed between the donor trimmed to one to two rings above the upper lobe origin and the host divided at its emergence from the mediastinum, the suture technique has evolved. Nine (32%) of 28 cases with early bronchial anastomoses with end-to-end suture and intercostal muscle wrap had ischemic or stenotic complications, but the telescoping technique without wrap in 164 bronchial anastomoses reduced the problem to 12% (19 of 164). Twelve anastomoses required temporary intraluminal stenting. Vascular anastomotic obstructions occurred in five arterial (excessive length 2, short allograft artery 1, restrictive suture or clot 2) and two venous (excessive length 1, restrictive suture or clot 1) connections. Suspicion of arterial obstruction was prompted by persisting pulmonary hypertension and reduced flow to the allograft measured by postoperative nuclear scan and hypoxia. Venous obstructions were suggested by persisting radiographic and clinical pulmonary edema. Modifications of earlier techniques have improved our early success in lung transplantation and might be considered by others entering this demanding field.