Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases.

The success of solid tumor growth and metastasis is dependent upon angiogenesis. Neovascularization within the tumor is regulated, in part, by a dual and opposing system of angiogenic and angiostatic factors. We now report that IP-10, a recently described angiostatic factor, as a potent angiostatic factor that regulates non-small cell lung cancer (NSCLC)-derived angiogenesis, tumor growth, and spontaneous metastasis. We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA). In contrast, levels of IP-10 were equivalent in either normal lung tissue or adenocarcinoma specimens. The neoplastic cells in specimens of SCCA were the predominant cells that appeared to express IP-10 by immunolocalization. Neutralization of IP-10 in SCCA tumor specimens resulted in enhanced tumor-derived angiogenic activity. Using a model of human NSCLC tumorigenesis in SCID mice, we found that NSCLC tumor growth was inversely correlated with levels of plasma or tumor-associated IP-10. IP-10 in vitro functioned as neither an autocrine growth factor nor as an inhibitor of proliferation of the NSCLC cell lines. Reconstitution of intratumor IP-10 for a period of 8 wk resulted in a significant inhibition of tumor growth, tumor-associated angiogenic activity and neovascularization, and spontaneous lung metastases, whereas, neutralization of IP-10 for 10 wk augmented tumor growth. These findings support the notion that tumor-derived IP-10 is an important endogenous angiostatic factor in NSCLC.

Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma.

We investigated the role of interleukin 8 (IL-8) in mediating angiogenesis in human bronchogenic carcinoma. Increased quantities of IL-8 were detected in tumor tissue as compared with normal lung tissue. Immunohistochemical staining of tumors revealed primary localization of IL-8 to individual tumor cells and demonstrated the capacity of tumor to elaborate IL-8. Functional studies that used tissue homogenates of tumors demonstrated the induction of both in vitro endothelial cell chemotaxis and in vivo corneal neovascularization. It is important to note that the addition of neutralizing antisera to IL-8 to these assays resulted in the marked and specific attenuation of these responses. Our observations definitively establish IL-8 as a primary mediator of angiogenesis in bronchogenic carcinoma and offer a potential target for immunotherapies against solid malignancies.

Achalasia. A morphologic study of 42 resected specimens.

Achalasia is characterized by failure of relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Few data are available regarding the morphologic features of achalasia, in particular its histologic progression. The esophagi of 42 patients with achalasia treated with total thoracic esophagectomy were examined histologically in order to systematically identify morphologic features of clinically unresponsive achalasia and to determine what could be learned about the disease's evolution. In all cases, myenteric ganglion cells within the esophageal body were markedly diminished, with 20 specimens having none. Twenty specimens had residual ganglion cells in the proximal esophagus, and 15 specimens had a few randomly distributed ganglion cells in the mid- and distal portions of the esophagus. Inflammation within myenteric nerves, present in all cases, generally consisted of a mixture of lymphocytes and eosinophils, occasionally with plasma and mast cells. Focal replacement of myenteric nerves by collagen occurred in all cases, and there was almost complete replacement in several cases. Actual destruction of the residual ganglion cells was not seen. The resected esophagi also shared extramyenteric morphologic features. Some features probably stemmed from physiologic obstruction, such as muscular hypertrophy, mainly of the muscularis propria (all cases), with secondary degeneration and fibrosis (29 cases), and eosinophilia of the muscularis propria (22 cases). Other changes, probably resulting from chronic stasis of ingested materials in the lumen, included diffuse squamous hyperplasia (all cases), lymphocytic mucosal esophagitis (28 cases), lymphocytic inflammation of the lamina propria and submucosa with prominent germinal centers (all cases), and submucosal periductal or glandular inflammation with complete loss of submucosal glands in half of the cases. One patient had high-grade squamous dysplasia, and another had superficially invasive squamous cell carcinoma. A third group of changes was probably due to previous esophagomyotomy, including abnormal gastroesophageal reflux, as shown by pH reflux testing (13 cases) and Barrett's mucosa (four cases). In one case of Barrett's there was low-grade dysplasia. Clinically unresponsive, surgically resected achalasia has almost total loss of ganglion cells, and widespread destruction of myenteric nerves has already occurred. The only active component is myenteric inflammation. However, it cannot be determined whether this inflammation is a manifestation of ongoing nerve destruction or whether it is a secondary phenomenon.

Tumor emboli from lung neoplasms involving the pulmonary vein.

Systemic tumor embolization during pulmonary resection for lung neoplasms is an uncommon but potentially catastrophic complication. In recent months, two patients undergoing pulmonary resection for bronchogenic carcinoma were found at operation to have tumor extending into a pulmonary vein. Both patients had systemic tumor embolization, one with a fatal outcome because of occlusion of the superior mesenteric artery. The possibility of systemic tumor embolization should be considered in patients with large, central tumors and particularly those that abut the pulmonary veins. The implications of such pulmonary vein involvement is reviewed, and an algorithm for postoperative evaluation and management of these patients is presented.

Catastrophic complications of the cervical esophagogastric anastomosis.

Recent enthusiasm for the cervical esophagogastric anastomosis has arisen because of its perceived low morbidity. Although catastrophic complications of a cervical esophagogastric anastomosis are unusual, they can and do occur, and prevention is possible if the potential for them is recognized. Among 856 patients undergoing a cervical esophagogastric anastomosis after transhiatal esophagectomy, catastrophic cervical infectious complications occurred in 11 patients (1.3%): vertebral body osteomyelitis (1), epidural abscess with neurologic impairment (2), pulmonary microabscesses from internal jugular vein abscess (1), tracheoesophagogastric anastomotic fistula (1), and major dehiscence necessitating anastomotic takedown (6). These complications became manifest from 5 to 85 days after the esophageal resection and reconstruction (mean 19 days). Leakage from a gastric suspension stitch placed in the anterior spinal ligament over the vertebral bodies resulted in a posterior gastric leak and either osteomyelitis or an epidural abscess in three patients, none of whom had evidence of extravasation on the routine barium swallow 10 days after operation. Cervical exploration for a presumed anastomotic leak led to the unexpected discovery of an abscess formed by the stomach and the adjacent wall of the internal jugular vein, which was ligated and resected. One patient without symptoms who was discharged from the hospital with a contained anastomotic leak on the postoperative barium swallow was readmitted 7 days later with a cervical tracheoesophagogastric anastomotic fistula of which he ultimately died. In 6 patients (7% of those who had anastomotic leaks) there was sufficient gastric ischemia or necrosis, or both, to necessitate takedown of the anastomosis and intrathoracic stomach, cervical esophagostomy, and insertion of a feeding tube. As a result of this experience, it is recommended that cervical gastric suspension sutures either be omitted entirely or placed in the fascia over the longus colli muscles anterior to the spine, but not directly into the prevertebral fascia overlying the vertebral bodies or cervical disks. All but minute cervical anastomotic leaks, even if apparently contained, are best drained rather than treated expectantly. Patients who remain febrile and ill after bedside drainage of a cervical esophagogastric anastomosis leak should undergo cervical reexploration in the operating room; major gastric ischemia or necrosis, or both, may warrant takedown of the anastomosis and intrathoracic stomach.

Pulmonary smooth muscle proliferation occurring after lung transplantation.

We report the first example of smooth-muscle proliferations occurring in an allograft lung implanted in a recipient who had end-stage emphysema. Smooth-muscle proliferations were detected 46 months following transplantation in a 53-year-old woman. The lesions involved the airways and were bronchoscopically undetectable. Posttransplant smooth-muscle tumors have been described in liver transplant patients and are thought to be due to Epstein-Barr virus. Evidence of virus infection was not found in the current case.

Intrathoracic esophageal perforation. The merit of primary repair.

Between 1976 and 1993, 22 patients with intrathoracic esophageal perforations, none associated with carcinoma, underwent primary repair regardless of the interval between perforation and the time of repair. Eighteen perforations were iatrogenic and four were spontaneous. The interval from perforation to operation was less than 12 hours in 10 patients, 12 to 24 hours in 3, and more than 24 hours in 9. Principles of repair included (1) a local esophagomyotomy proximal and distal to the tear to expose the mucosal defect and normal mucosa beyond, (2) debridement of the mucosal defect and closure over a bougie, and (3) reapproximation of the muscle. The repair was buttressed with muscle or pleura in five patients. Associated distal obstruction caused by reflux stricture was treated with dilation and fundoplication in four patients. Of the four patients with achalasia, two underwent esophagomyotomy with a fundoplication and one underwent myotomy alone. There was one death. The esophageal repair healed primarily in 17 patients (80%). Four patients, three of whom underwent repair more than 24 hours after the perforation, had leaks at the site of repair. All four fistulas eventually healed with drainage alone, two with simple tube thoracostomy and two with rib resection and empyema tube placement. In the absence of cancer or an irreversible distal obstruction, meticulous repair of an intrathoracic esophageal perforation is the preferred approach, regardless of the duration of the injury, inasmuch as primary healing is likely, and the morbidity associated with prolonged drainage or diversion may be avoided.

Transthoracic needle aspiration in patients with severe emphysema. A study of lung transplant candidates.

PURPOSE: To describe the risks of transthoracic needle aspiration (TTNA) in a population of patients with severe lung disease: candidates for lung transplantation. MATERIALS AND METHODS: Eight of 190 patients evaluated for lung transplantation underwent TTNA of nine pulmonary nodules (mean diameter, 14 mm; range, 0.8 to 2.2 cm). We evaluated pneumothorax rate, chest tube rate, duration of placement, and pulmonary function test results. RESULTS: All patients had emphysema; two had alpha 1-antitrypsin deficiency. The mean FEV1 of all patients was 0.64 L (22% of predicted; range, 17 to 28%), indicating severe air-flow obstruction. Six patients required a chest tube (50%); three chest tubes were placed emergently on the CT scanner table. Three patients required a second chest tube for persistent air leak. Tubes were in place for 1 to 22 days (mean, 10 days). One patient had chest tubes for 22 days and required intubation. CONCLUSION: TTNA in patients with marked emphysema is complicated by a high incidence of pneumothorax, rapid development of tension pneumothorax and chest tube placement. Since nodules in lung transplant candidates may represent bronchogenic carcinoma, serial CT scans to demonstrate lesion stability or growth, or thoracoscopic resection should be considered as an alternate approach to TTNA to avoid the significant morbidity of the procedure in these patients.

Alterations of K-ras, p53, and erbB-2/neu in human lung adenocarcinomas.

The development of human adenocarcinoma of the lung involves multiple genetic changes including activation of oncogenes and loss of tumor suppressor genes. Patients whose lung tumors contain K-ras oncogene mutation, accumulation of the protein product of the tumor suppressor gene p53, or erbB-2/neu oncoprotein overexpression have been shown to have a worse prognosis. We examined these three genetic indicators in 29 lung adenocarcinomas to determine whether these markers are present in the same tumors or if they represent molecular changes that define different subsets of patients. P53 nuclear protein accumulation and erbB-2/neu protein overexpression were determined by immunohistochemical analysis of cryostat sections of tumor specimens and corresponding normal lung tissue. K-ras mutations were detected by radiolabeled oligonucleotide probes, specific for the various twelfth codon mutations, hybridized to exon 1 of K-ras, which was amplified by the polymerase chain reaction. Increased nuclear accumulation of p53 protein was found in 11 adenocarcinomas (38%). All of the p53 positive tumors were found to show high level staining and homogeneous expression of erbB-2/neu protein. K-ras mutations were detected in seven tumors (24%), all of which overexpressed erbB-2/neu. The presence of a K-ras mutation did not correlate with p53 accumulation. In total, 93% of the tumors were found to overexpress erbB-2/neu, the highest being in one tumor with erbB-2/neu gene amplification. The presence of K-ras twelfth codon mutation was associated with increased cigarette smoking. In conclusion, erbB-2/neu overexpression is a common event in lung adenocarcinomas. Furthermore, the presence of K-ras mutation and p53 protein accumulation define separate groups of patients. The mechanisms by which these genetic alterations interact or adversely affect prognosis is unknown.

Preoperative echocardiographic evaluation of patients referred for lung volume reduction surgery.

BACKGROUND: The most efficient preoperative assessment for lung volume reduction surgery (LVRS) in patients with advanced emphysema is undefined. This study analyzed the preoperative assessment of patients by surface echocardiography (without and with dobutamine infusion), the results of which were used to exclude patients with significant pre-existing cardiac disease, a contraindication to LVRS, from the surgery. SETTING: A university-based, tertiary care referral center. METHODS: Patients with emphysema who met initial LVRS screening criteria underwent resting and stress surface echocardiography with Doppler imaging. Patients were evaluated prospectively for perioperative cardiac complications. RESULTS: Between July 1994 and December 1996, 503 candidates for LVRS were evaluated. Of these, 207 patients (81.8%) who had echocardiography performed at our institution formed the primary study group. Images were adequate for the analysis of chamber sizes and function in 206 patients (99.5%) undergoing resting echocardiography, and the images were adequate for wall motion analysis in 172 of 174 patients (98.9%) undergoing functional testing. Right heart abnormalities were common (40.1%). Significant pulmonary hypertension (> 35 mm Hg) was uncommon (5 patients, 5.4%) among the 92 patients who subsequently underwent right heart catheterization. Occult ischemia, left ventricular dysfunction, and valvular abnormalities also were uncommon. Thus, although Doppler imaging estimates of right ventricular systolic pressure were imperfect, echocardiographic findings of normal right heart anatomy and function excluded significant pulmonary hypertension. Ninety patients (43%) eventually underwent LVRS (70 bilateral and 20 unilateral). A total of 13 perioperative cardiac events occurred in 10 patients, 6 of whom had undergone preoperative echocardiography. No patient suffered acute myocardial infarction or cardiac death. CONCLUSIONS: Despite potential limitations due to severe obstructive lung disease, surface echocardiographic imaging is a feasible, noninvasive tool in this patient population to identify patients with evidence of cor pulmonale that suggests pulmonary hypertension. The routine use of surface resting and stress echocardiography for preoperative screening obviates the need for invasive right heart catheterization in many patients and results in a low incidence of significant perioperative cardiac complications.

Dobutamine stress echocardiography for the preoperative evaluation of patients undergoing lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery has been proposed as a bridge to lung transplantation and as definitive therapy for advanced chronic obstructive lung disease. However, patient selection criteria and optimal preoperative assessment have not been clearly defined. OBJECTIVE: We investigated the feasibility, safety, and value of dobutamine stress echocardiography as a predictor of major early cardiac events in patients who underwent lung volume reduction surgery. METHODS: The study population consisted of 46 patients (21 men and 25 women, mean age 59 +/- 9 years) who underwent dobutamine stress echocardiography (maximum dose 40 microg. kg(-1). min(-1) plus atropine if needed) 180 days or less before lung volume reduction surgery. Adverse cardiac events were prospectively defined and tabulated during hospitalization after the operation and at subsequent outpatient visits. RESULTS: Dobutamine stress echocardiography was interpretable in 45 of 46 (98%) patients. There were no adverse events during testing. The studies revealed normal left ventricular systolic function at rest in all patients and normal right ventricular function in all patients but one. Thirteen patients had right ventricular enlargement. Estimated right ventricular systolic pressure was mildly elevated (>40 mm Hg) in 5 patients. Four patients (9%) had stress tests positive for ischemia. There were no perioperative deaths. Follow-up was available for 44 of 45 patients at a duration of 20.0 +/- 7.0 months. Two major adverse cardiac events occurred in the same patient in whom the results of dobutamine stress echocardiography were positive for ischemia (positive predictive value 25%, 95% confidence interval 0% to 83%; negative predictive value 100%, 95% confidence interval 90 to 100%). CONCLUSION: Despite end-stage chronic obstructive lung disease and poor ultrasound windows, dobutamine stress echocardiography is feasible and safe in patients undergoing evaluation for lung volume reduction surgery. It yields important information on right and left ventricular function and has an excellent negative predictive value for early and late adverse cardiac events.

Pulmonary function in single lung transplantation for chronic obstructive pulmonary disease.

The primary determinants of pulmonary function after heart-lung or double lung transplantation are the volume and compliance of the recipient's thoracic cage. This study evaluated the influence of recipient chest wall factors on static and dynamic lung volumes after single lung transplantation for chronic obstructive pulmonary disease. Fourteen patients with chronic obstructive pulmonary disease received 15 single lung transplants (one retransplant). Posttransplantation follow-up data at 3 and 6 months, in the absence of infection or rejection, were available in nine patients. Overall pulmonary function at 6 months improved from preoperative levels to 55% to 65% of predicted values (forced vital capacity 38% to 55%, forced expiratory volume at 1 second 18% to 55%, maximum voluntary ventilation 21% to 65%), and allograft-specific pulmonary function improved to nearly normal predicted single-lung values (forced vital capacity 89%, forced expiratory volume at 1 second 90%, maximum voluntary ventilation 105%). Postoperative pulmonary function in these patients correlated significantly with preoperative thoracic volume measured by planimetry of chest radiographs. No correlation between postoperative pulmonary function was demonstrated with either the estimated volume of donated lung tissue or relative donor-to-recipient size matching. These findings support the concept that recipient chest wall factors determine postoperative pulmonary function in patients undergoing single lung transplantation for chronic obstructive pulmonary disease. Furthermore, the allograft lung functions at a normal level for the recipient and does not appear to be constrained by hyperinflation of the contralateral lung.

Sonomicrometric regional diaphragmatic shortening in awake sheep after thoracic surgery.

Through a right thoracotomy in seven sheep we chronically implanted sonomicrometry crystals and electromyographic electrodes in the costal and crural diaphragmatic regions. Awake sheep were studied during recovery for 4-6 wk, both during quiet breathing (QB) and during CO2 rebreathing. Tidal volume, respiratory frequency, and esophageal and gastric pressures were studied before and after surgery. Normalized resting length (LFRC) was significantly decreased for the costal segment on postoperative day 1 compared with postoperative day 28. Fractional costal shortening both during QB and at 10% end-tidal CO2 (ETCO2) increased significantly from postoperative days 1 to 28, whereas crural shortening did not change during QB but progressively increased at 10% ETCO2. Maximal costal shortening during electrophrenic stimulation was constant at 40% LFRC during recovery, although maximal crural shortening increased from 23 to 32% LFRC. Minute ventilation, tidal volume, and transdiaphragmatic pressure at 10% ETCO2 increased progressively after thoracotomy until postoperative day 28. Our results suggest there is profound diaphragmatic inhibition after thoracotomy and crystal implantation in sheep that requires at least 3-4 wk for stable recovery.

Tolerance to low-dose endotoxin in awake sheep.

Dose response and tolerance to a small intravenous dose of Serratia marcescens lipopolysaccharide (LPS) were studied in awake sheep. Core temperature significantly increased after a dose of 0.002 micrograms/kg; changes in pulmonary arterial pressure, pulmonary vascular resistance, plasma thromboxane B2, and circulating leukocyte concentration occurred after 0.02 micrograms/kg; plasma 6-keto-prostaglandin F1 alpha increased after 0.2 micrograms/kg. Development of acute tolerance was studied by injection of S. marcescens LPS (0.02 micrograms/kg iv) on 3 consecutive days: pulmonary arterial pressure and thromboxane B2 levels were significantly lower than controls after the second dose, whereas fever and the degree of leukopenia were not diminished until the third dose. After intravenous administration of LPS given in increasing doses from 0.1 to 3.2 micrograms/kg three times weekly over 7 wk, there were no measurable changes in any of the above parameters after challenge with S. marcescens LPS (0.02 micrograms/kg) after a 1-wk rest period. In awake sheep, small intravenous doses of LPS can cause physiologically important changes of the pulmonary circulation and can alter the hemodynamic and eicosanoid mediator responses to subsequent challenges with LPS. Large intravenous doses of LPS can ablate the physiological responses to subsequent small doses of LPS.

Functional outcome after surgical treatment of esophageal perforation.

BACKGROUND: The functional results after treatment of intrathoracic esophageal perforations have been poorly documented. METHODS: A retrospective review of 42 patients who underwent treatment of intrathoracic esophageal perforation associated with benign esophageal disease was performed. RESULTS: Of 42 patients treated for esophageal perforation, 25 underwent primary repair, 15 underwent esophagectomy and reconstruction, 1 underwent cervical esophagostomy and drainage followed by esophageal resection, and 1 had drainage alone followed by primary repair. Among the patients treated with primary repair, at least one additional operation was required in 13 patients. Of the 15 patients treated with esophagectomy and reconstruction, none required further operative treatment. Follow-up averaged 3.7 years, and of the 36 survivors available for follow-up, 18 (50%) required at least one esophageal dilation postoperatively, and 3 (8.3%) have required regular dilations. Subjectively, 19 of 36 patients (53%) indicate that their swallowing is better than before perforation, it was the same in 12 (33%), and worse in 4 (11%). CONCLUSIONS: In conclusion, approximately one third of patients surviving primary repair of esophageal perforations have continued difficulty with swallowing, which often requires esophageal dilations or esophageal reconstructive procedures, or a combination of both. Optimal long-term results are achieved when primary repair is performed in patients with motor disorders or a "normal" esophagus. Esophagectomy is a better option in those patients with strictures or diffuse esophageal disease.

Adjuvant treatment using transfer factor for bronchogenic carcinoma: long-term follow-up.

Transfer factor, a dialyzable lymphocyte extract that may act as an immune stimulator by transferring antigen-specific immunity between genetically dissimilar individuals, was administered in a prospective, randomized study to patients with non-small cell bronchogenic carcinoma. Between 1976 and 1982, 63 patients who underwent pulmonary resection, mediastinal lymph node dissection, and, when indicated by the presence of mediastinal lymph node involvement, mediastinal irradiation were randomized into two groups. Group 1 (n = 28) received 1 mL of pooled transfer factor at 3-month intervals after operation; group 2 (n = 35 ) served as controls and received saline solution. There were no statistically significant differences between the two groups with respect to age, sex, tumor histology, stage of disease, or extent of resection. One patient was lost to follow-up at 96 months; follow-up was complete in all others through July 1990. In patients receiving transfer factor, the 2-, 5-, and 10-year survival rates were 82%, 64%, and 43% respectively, whereas in controls they were 63%, 43%, and 23%. Survival in patients receiving transfer factor was consistently better than in those receiving placebo. Furthermore, survival in patients receiving transfer factor was greater at all stages of disease for both adenocarcinoma and squamous cell carcinoma. Although these long-term results were not statistically significant using survival analysis with covariates (p = 0.08), they confirm our previously reported short-term findings suggesting that administration of transfer factor, either through nonspecific immune stimulation, enhancement of cell-mediated immunity, or an as yet undefined mechanism, can improve survival in patients with bronchogenic carcinoma.

Combined lung volume reduction and mitral valve reconstruction.

Combined lung volume reduction and mitral valve reconstruction was performed in a 66-year-old man with end-stage emphysema and severe mitral regurgitation. Quality of life, pulmonary function, 6-minute walk, echocardiographic degree of mitral regurgitation, and New York Heart Association heart failure classification all improved substantially. A lung volume reduction operation can safely be combined with complex cardiac operations for patients with disabling dyspnea of a multifactorial nature.

Esophagogastrectomy via left thoracophrenotomy.

Esophagogastrectomy is generally considered to be the treatment of choice for resectable tumors of the esophagus. Although many approaches and techniques have been advocated, since April 1983 we have used a left thoracophrenotomy approach for most lesions of the lower two thirds of the esophagus and gastric cardia. Stapling instruments have been used for mobilization of the stomach and fashioning of the esophagogastric anastomosis. One-hundred fifteen patients undergoing resection of malignant tumors with this technique were retrospectively reviewed. Perioperative mortality was 8.7% (10/115). The rate of anastomotic leakage was 1.7% (2/115), and benign narrowing of the anastomosis requiring dilation developed in 16 patients. The rate of recurrent anastomotic tumor was 4.3%. Eighteen patients had complications, and the mean postoperative hospital stay was 13 days. Survival at 3 years was 22.1%. During the period of study, 22 patients underwent esophageal resection by some other approach; the reasons for this are described. The advantages of the left thoracophrenotomy approach are discussed.

Mycophenolate mofetil for obliterative bronchiolitis syndrome after lung transplantation.

BACKGROUND: The development of obliterative bronchiolitis after lung transplantation portends a poor long-term outcome because of progressive decline in allograft function. There are currently no effective means of treating this condition. METHODS: Thirteen patients in whom obliterative bronchiolitis syndrome developed after lung transplantation were treated with mycophenolate mofetil, an antimetabolite immunosuppressant, at a dose of 1.5 g orally twice daily. Patients were followed up clinically and with pulmonary function testing. RESULTS: Duration of mycophenolate mofetil therapy ranged from 1 week to 24 months (mean duration, 11.4 months). Pulmonary function test results stabilized in the majority of patients with no significant further decline in forced expiratory volume in 1 second. Two patients died of progressive obliterative bronchiolitis, 1 patient is alive with progressive disease, and 1 patient died of an acute infection. The drug was discontinued in 2 additional patients. In no patient did severe leukopenia or cytomegalovirus infection develop; 1 patient had a fungal infection, and 7 patients experienced gastrointestinal side effects. CONCLUSIONS: In the setting of obliterative bronchiolitis syndrome, mycophenolate mofetil is generally well tolerated and is associated with stabilization of pulmonary function test results. These findings suggest that the otherwise progressive process of obliterative bronchiolitis can be slowed.

Extracorporeal life support after heart or lung transplantation.

Extracorporeal life support (ECLS) has been used in 10 patients after heart (5 patients), lung (3 patients), and heart-lung (2 patients) transplantation. The age range was 7 months to 55 years. Cardiopulmonary failure leading to institution of ECLS was due to acute postoperative organ malfunction in 4 patients (2 survived), subacute organ malfunction in 3 patients (none survived), and late rejection or infection in 3 patients (2 survived). Neurologic complications occurred in 3 patients (1 survived) and bleeding, in 5 patients (2 survived). Six patients (60%) were successfully weaned from ECLS, and 4 (40%) survived to leave the hospital. Survival was associated with younger age, shorter duration of ECLS, and longer interval from operation to initiation of ECLS but not to reason for initiating ECLS. Extracorporeal life support is feasible for sustaining both adults and children after heart, lung, or heart-lung transplantation. Best results were obtained in patients with conditions that, in retrospect, were treatable and reversible within days. More experience is needed to predict preoperatively which patients will benefit most from ECLS.