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.

Epithelial-neutrophil activating peptide (ENA-78) is an important angiogenic factor in non-small cell lung cancer.

We report here the role of the CXC chemokine, epithelial neutrophil activating peptide (ENA-78), as an angiogenic factor in human non-small cell lung cancer (NSCLC). In freshly isolated human specimens of NSCLC, elevated levels of ENA-78 were found that strongly correlated with the vascularity of the tumors. In a SCID mouse model of human NSCLC tumorigenesis, expression of ENA-78 in developing tumors correlated with tumor growth in two different NSCLC cell lines. Furthermore, passive immunization of NSCLC tumor-bearing mice with neutralizing anti-ENA-78 antibodies reduced tumor growth, tumor vascularity, and spontaneous metastases, while having no effect on the proliferation of NSCLC cells either in vitro or in vivo. These findings suggest that ENA-78 is an important angiogenic factor in human NSCLC.

Fas/APO-1 (CD95) is not translocated to the cell membrane in esophageal adenocarcinoma.

This study describes Fas (CD95) expression in Barrett's esophagus, adenocarcinomas of the esophagus, and three esophageal adenocarcinoma cell lines. Immunohistochemical analysis of Barrett's esophagus demonstrated cell surface expression of Fas protein. In contrast, 30.5% of esophageal adenocarcinomas examined by immunohistochemical analysis demonstrated faint cytoplasmic staining, and 69.5% were negative for Fas. Similar levels of Fas mRNA were identified in tumors compared to mRNA levels in esophageal squamous mucosa or Barrett's esophagus. An approximately Mr 48,000 Fas protein was identified by Western blot analysis in tumors that were negative for Fas expression by immunohistochemical analysis. The esophageal adenocarcinoma cell line Seg-1 was negative for Fas expression by immunohistochemical analysis, but Western blot analysis demonstrated abundant, appropriately sized Fas protein. In agreement with the immunohistochemical analysis, flow cytometry of Seg-1 showed minimal amounts of Fas on the cell surface, which correlated with resistance to Fas-mediated apoptosis. No mutations in the Seg-1 Fas coding sequence or exon 1 were identified by sequence analysis. This was confirmed by transient transfection of COS cells with expression vectors generated from the Seg-1 Fas cDNA, which resulted in cell surface expression of the Fas protein. Stable transfection of Seg-1 with a Fas expression vector did not result in efficient Fas expression on the cell surface. Seg-1 cells, transiently transfected with a Fas-FLAG expression vector and examined for protein expression using confocal microscopy and an anti-FLAG antibody, showed that the Fas-FLAG protein was not present on the cell surface but was present in the cytoplasm. Taken together, these results indicate that expression of Fas on the cell surface by esophageal adenocarcinoma is reduced. In an esophageal adenocarcinoma cell line, wild-type Fas protein is retained in the cytoplasm, and this correlates with resistance to Fas-mediated apoptosis. The retention of wild-type Fas protein within the cytoplasm may represent a mechanism by which malignant cells evade Fas-mediated apoptosis.

The CXC chemokine, monokine induced by interferon-gamma, inhibits non-small cell lung carcinoma tumor growth and metastasis.

Angiogenesis is an absolute requirement for tumor growth beyond 2 mm3 in size. The balance in expression between opposing angiogenic and angiostatic factors controls the angiogenic process. The CXC chemokines are a group of chemotactic cytokines that possess disparate activity in the regulation of angiogenesis. Non-small cell lung carcinoma (NSCLC) has an imbalance in expression of ELR+ (angiogenic) compared with ELR- (angiostatic) CXC chemokines that favors angiogenesis and progressive tumor growth. We found that the level of the ELR- CXC chemokine MIG (monokine induced by interferon gamma) in human specimens of NSCLC was not significantly different from that found in normal lung tissue. These results suggested that the increased expression of ELR+ CXC chemokines found in these tumor samples is not counterregulated by a concomitant increase in the expression of the angiostatic ELR-CXC chemokine MIG. This would result in an even more profound imbalance in the expression of regulatory factors of angiogenesis that would favor neovascularization. We hypothesized that MIG might be an endogenous inhibitor of NSCLC tumor growth in vivo and that reconstituion of MIG in the tumor microenvironment would result in the inhibition of tumor growth and metastasis. In support of this hypothesis, we demonstrate here that overexpression of the ELR-CXC chemokine MIG, by three different strategies including gene transfer, results in the inhibition of NSCLC tumor growth and metastasis via a decrease in tumor-derived vessel density. These findings support the importance of the ELR- CXC chemokine MIG in inhibiting NSCLC tumor growth by attenuation of tumor-derived angiogenesis. Furthermore, these findings demonstrate the potential of gene therapy as an alternative means to deliver and overexpress a potent angiostatic CXC chemokine.

Eliminating the cervical esophagogastric anastomotic leak with a side-to-side stapled anastomosis.

BACKGROUND: Although the acute postoperative complications of a cervical esophagogastric anastomosis are less than those with an intrathoracic esophageal anastomosis, the long-term sequelae of a cervical anastomotic leak are not as minor as initially reported. Nearly 50% of cervical anastomotic leaks result in an anastomotic stricture, and the subsequent need for chronic dilatations negates the merits of an operation intended to restore comfortable swallowing. OBJECTIVE: This study was undertaken to determine whether construction of a side-to-side stapled cervical esophagogastric anastomosis after transhiatal esophagectomy could reliably eliminate the majority of anastomotic leaks. METHODS: In 114 consecutive patients undergoing transhiatal esophagectomy, a functional side-to-side cervical esophagogastric anastomosis was constructed with the Auto Suture Endo-GIA II stapler (United States Surgical Corporation, Auto Suture Company Division, Norwalk, Conn) applied directly through the cervical wound. This side-to-side stapled anastomosis has 3 rows of staples. Early postoperative anastomotic morbidity, subsequent need for anastomotic dilatations, and patient satisfaction with swallowing were evaluated. RESULTS: Before the side-to-side stapled anastomosis, the incidence of cervical esophagogastric anastomosis leak in over 1000 patients undergoing transhiatal esophagectomy having a manually sewn anastomosis varied from 10% to 15%. Among the 111 survivors of transhiatal esophagectomy and a side-to-side stapled anastomosis, there were 3 (2.7%) clinically significant anastomotic leaks. This lowered incidence of leaks has contributed to reduction in the average length of stay after an uncomplicated transhiatal esophagectomy to 7 days and has provided more comfortable swallowing, ease of subsequent esophageal dilatations, and greater patient satisfaction. CONCLUSIONS: Construction of the cervical esophagogastric anastomosis with a side-to-side stapled anastomosis greatly reduces the frequency of anastomotic leaks and later strictures. The side-to-side stapled anastomosis is a major technical advance in the progression of refinements of transhiatal esophagectomy and a cervical esophagogastric anastomosis.

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.

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.

The regional effect of retrograde cardioplegia in areas of evolving ischemia.

Retrograde cardioplegia (RCP) is often used for myocardial protection during coronary bypass grafting, but the regional effect of RCP in areas of evolving ischemia is unknown. We examined the functional and metabolic indices of regional myocardial preservation following acute coronary occlusion with evolving ischemia in a canine model. Following the institution of 37 degrees C cardiopulmonary bypass in 14 dogs, the left anterior descending artery (LAD) was occluded for 15 min. The hearts were then subjected to 90 min of cardioplegic arrest (12 degrees C, 15 mL/kg every 30 min). Seven had antegrade cardioplegia (ACP) alone, while seven had ACP until arrest, then RCP. No topical cooling was used. The LAD occlusion was released after the first bolus of cardioplegia. Regional temperature and pH were measured in the LAD and circumflex (nonischemic) distributions. After 90 min of ischemia and 30 min of reperfusion, all dogs were weaned from bypass. Postischemic function was determined globally by the return of developed pressure (%dP/dt) and regionally by ultrasonic wall crystals. End-ischemic ATP preservation in the LAD distribution was assessed by HPLC (mm ATP/mg protein). Results show that regional functional and metabolic indices were better maintained with RCP in the ischemic LAD distribution. Although only moderate reduction of global function was seen with ACP, the severe reduction noted in LAD regional wall motion with ACP reflects poor regional protection that can be significantly improved in evolving ischemia with RCP.

The effect of intramyocardial pH on functional recovery in neonatal hearts receiving St. Thomas' Hospital cardioplegic solution during global ischemia.

The experiments in the present study were designed to address two issues: Is it possible to manipulate intramyocardial pH in neonatal hearts with different buffers in cardioplegic solution and, if so, do differences in intramyocardial pH during ischemia influence functional recovery? Isolated working hearts from 7- to 10-day-old rabbits underwent 60 minutes of cardioplegic arrest at 37 degrees C with cardioplegic washouts at the onset of ischemia and at 30 minutes. Hearts were reperfused with oxygenated physiologic saline solution (pH = 7.4), returned to the working mode for 30 minutes, and hemodynamic measurements were obtained to compare with baseline values. Intramyocardial pH was held constant during the ischemic interval by infusing cardioplegic solution containing different buffers: histidine (pK 6.0 at 37 degrees C), bicarbonate (pK 6.4), or tromethamine (pK 8.1). The intramyocardial pH was measured continuously with a Khuri glass electrode system (Vascular Technology, Inc., North Chelmsford, Mass.). Cardioplegic solutions buffered to pH values of 6.0 (histidine), 7.4 (bicarbonate), and 8.0 (tromethamine) were associated with ischemic intramyocardial pH values of 6.3 +/- 0.03, 7.02 +/- 0.05, and 7.88 +/- 0.06, respectively. Functional recovery was best in the acidic (histidine) and worst in the basic (tromethamine) groups. Recoveries of developed pressure, the rate of rise of pressure over time, and aortic flow were significantly better for each parameter in the bicarbonate-treated compared with the tromethamine-treated hearts (p less than 0.005). Recovery in the histidine group, however, was superior to that in both the bicarbonate-treated and the tromethamine-treated hearts (p less than 0.005). Regression analysis demonstrated that a significant inverse relationship existed between functional recovery and intramyocardial pH, supporting the conclusions that intramyocardial pH is an important determinant of functional recovery in the neonatal heart and that acidic conditions during normothermic ischemia optimize preservation of myocardial function.

Spectrum of Aspergillus infection in lung transplant recipients: case series and review of the literature.

STUDY OBJECTIVES: (1) To define the incidence and natural history of Aspergillus colonization and infection in lung transplant recipients, and (2) to assess the impact of prophylaxis, surveillance, and therapy on the incidence and outcome of the disease. DESIGN: Retrospective review of 133 consecutive single or bilateral lung transplantations performed at a single institution, and review of the published literature. RESULTS: Airway colonization, isolated tracheobronchitis, and invasive pneumonia due to Aspergillus species occurred in 29%, 5%, and 8% of our series, and in 26%, 4%, and 5% of the pooled published data (all series, including ours), respectively. Greater than 50% of all diagnoses were made in the first 6 months after transplantation in both our series and the published literature. Incidence of progression from airway colonization to invasive disease was 1 in 38 in our series and 3 of 97 (3%) in the pooled published data. In patients with isolated tracheobronchitis, all 6 patients in our series and 41 of 50 patients (82%) in all published series, including ours, responded to antifungal therapy and/or surgical debridement. Among patients with invasive pneumonia or disseminated disease, however, 5 of 10 patients in our series and 26 of 64 patients (41%) in the pooled series survived their infection. CONCLUSIONS: The role of antifungal therapy in Aspergillus airway colonization in lung transplant recipients is unclear. Data support a strategy of scheduled screening bronchoscopy followed by aggressive treatment for isolated Aspergillus tracheobronchitis in lung transplant recipients.

Recovery of the neonatal heart after normothermic ischemia. Effect of oxygen and catalase.

The objective of this study was to determine the effect of oxygen and the oxygen radical-scavenging enzyme catalase on the neonatal rabbit heart exposed to global ischemia. The experiments were performed with an isolated neonatal (7 to 10 days of age) working heart model in which normothermic (37 degrees C) ischemia was produced for 60 minutes. Left ventricular developed pressure, ratio of change of ventricular pressure to change in time, and aortic flow were measured before ischemia and 30 minutes after reperfusing the hearts with physiologic saline solution. In the control group (ischemia only), developed pressure and ratio of change of ventricular pressure to change in time recovered to 27% +/- 3% (mean +/- standard error of the mean) and 24% +/- 7% of baseline; the hearts were incapable of ejecting (aortic flow = 0). Treatment of hearts before and after ischemia with catalase (150 units/ml of perfusate) was studied in a second group (control plus catalase), but functional recovery (developed pressure = 32% +/- 1%; ratio of change of ventricular pressure to change in time = 24% +/- 2%, and aortic flow = 0) was not significantly different from the control group. The effect of washout midway through the ischemic period with a low oxygen (oxygen concentration less than 35 mm Hg) solution was measured in a third group (hypoxic physiologic saline solution). Functional recovery (developed pressure = 13% +/- 3%; ratio of change of ventricular su pressure to change in time = 13% + 2%; aortic flow = 0) was not significantly different from the control and control plus catalase groups. In marked contrast were the effects of washout with an oxygenated (oxygen concentration greater than 500 mm Hg) solution (oxygenated physiologic saline solution) in which functional recovery (developed pressure = 78% +/- 3%; ratio of change of ventricular pressure to change in time = 80% +/- 3%; aortic flow = 39% +/- 9%) was significantly better than in the control, control plus catalase, and hypoxic physiologic saline solution groups. Use of modified St. Thomas' Hospital cardioplegic solution (cardioplegic solution group) during the ischemic period also resulted in substantial functional recovery (developed pressure = 80% +/- 3%; ratio of change of ventricular pressure to change in time = 78% +/- 5%; aortic flow = 64% +/- 7%) that did not differ significantly from that in the oxygenated physiologic saline solution group.(ABSTRACT TRUNCATED AT 400 WORDS)

An artificial lung reduces pulmonary impedance and improves right ventricular efficiency in pulmonary hypertension.

OBJECTIVE: Artificial lungs may have a role in supporting patients with end-stage lung disease as a bridge or alternative to lung transplantation. This investigation was performed to determine the effect of an artificial lung, perfused by the right ventricle in parallel with the pulmonary circulation, on indices of right ventricular load in a model of pulmonary hypertension. METHODS: Seven adult male sheep were connected to a low-resistance membrane oxygenator through conduits anastomosed end to side to the pulmonary artery and left atrium. Banding of the distal pulmonary artery generated acute pulmonary hypertension. Data were obtained with and without flow through the device conduits. Outcome measures of right ventricular load included hemodynamic parameters, as well as analysis of impedance, power consumption, wave reflections, cardiac efficiency, and the tension-time index. RESULTS: The model of pulmonary hypertension increased all indices of right ventricular load and decreased ventricular efficiency. Allowing flow through the artificial lung significantly reduced mean pulmonary artery pressure, zero harmonic impedance, right ventricular power consumption, amplitude of reflected waves, and the tension-time index. Cardiac efficiency was significantly increased. CONCLUSIONS: An artificial lung perfused by the right ventricle and applied in parallel with the pulmonary circulation reduces ventricular load and improves cardiac efficiency in the setting of pulmonary hypertension. These data suggest that an artificial lung in this configuration may benefit patients with end-stage lung disease and pulmonary hypertension with right ventricular strain.

Improving results with first-stage palliation for hypoplastic left heart syndrome.

Between January 1990 and February 1993, 73 patients underwent first-stage reconstruction for hypoplastic left heart syndrome at the University of Michigan Medical Center. During this period, surgical reconstruction remained essentially constant and consisted of a pulmonary artery-to-aorta anastomosis with allograft augmentation of the ascending, transverse, and proximal descending aorta, restriction of pulmonary blood flow with a polytetrafluoroethylene shunt from the innominate artery to the central pulmonary artery confluence, and atrial septectomy. Hospital survival was 62 of 73 patients, 85% (70% confidence limits: 80% to 89%). These results stand in marked contrast to those obtained during the earlier years of our experience from 1986 to 1989 when only 21 of 50 patients (42%, 70% confidence limits: 35% to 49%) survived (p = 0.001). Among the most recent group of patients, only 2 of 7 patients older than 1 month of age at operation survived, whereas 60 of 66 (91%, 70% confidence limits: 87% to 94%) patients younger than 1 month of age survived (p = 0.0001). Anatomic subtype and ascending aortic diameter were not predictive of survival. Actuarial survivals for those patients younger than 1 month of age at the first-stage operation, including hospital deaths and subsequent operative procedures, were 81%, 74%, and 74% at 6 months, 1 year, and 2 years, respectively. These results indicate that survival for patients after first-stage reconstruction for hypoplastic left heart syndrome has significantly improved in recent years. Older age was a strong risk factor, with a hospital survival of 91% for those patients undergoing first-stage palliation within the first month of life. These data have important implications for the type of operative intervention and its timing.

Critical aortic stenosis in the neonate. A comparison of balloon valvuloplasty and transventricular dilation.

The optimal treatment of critical aortic stenosis in the neonate and infant remains controversial. We compared transventricular dilation using normothermic cardiopulmonary bypass and percutaneous balloon aortic valvuloplasty with respect to early and late survival, relief of aortic stenosis, degree of aortic insufficiency, left ventricular function, and freedom from reintervention. Between July 1987 and July 1993, 30 neonates and infants underwent transventricular dilation or balloon aortic valvuloplasty for critical aortic stenosis. The patients in the transventricular dilation group (n = 21) ranged in age from 1 to 59 days (mean age 18.0 days +/- 19.1 days) and the balloon aortic valvuloplasty group (n = 9) from 1 to 31 days (mean age 10.0 days +/- 9.0 days). There were no significant differences in weight, body surface area, or aortic anulus diameter between the two groups (p = 1.0). Associated cardiovascular anomalies were more common in the transventricular dilation group (48%) than in the balloon aortic valvuloplasty group (11%). After intervention, the degree of residual aortic stenosis and insufficiency was equivalent in the two groups as assessed by postprocedural Doppler echocardiography. Ejection fraction improved within both groups (transventricular dilation 39% +/- 20.2% versus 47% +/- 22.0%; balloon aortic valvuloplasty 51% +/- 16.1% versus 62% +/- 8.4%), and there was no significant difference between groups. The left ventricular mass/volume ratio increased within both groups (p < 0.05) but with no significant difference between groups (transventricular dilation 1.4 +/- 0.5 gm/ml versus 1.8 +/- 0.6 gm/ml; balloon aortic valvuloplasty 1.1 +/- 0.6 gm/ml versus 1.7 +/- 0.4 gm/ml). Early mortality in the transventricular dilation group was 9.5% and in the balloon aortic valvuloplasty group, 11.1%. There was one late death in the transventricular dilation group. Four patients from the transventricular dilation group (19%) and two patients from the balloon aortic valvuloplasty group (22%) required reintervention for further relief of aortic stenosis. We conclude that both transventricular dilation and balloon aortic valvuloplasty provide adequate and equivalent relief of critical aortic stenosis. The treatment strategy adopted should depend on other factors, including associated cardiovascular anomalies, vascular access, preoperative condition, and the technical expertise available at each institution.

Weight gain after lung volume reduction surgery is not correlated with improvement in pulmonary mechanics.

STUDY OBJECTIVES: Malnutrition and low body weight are common in patients with emphysema. Previous work has demonstrated correlation between severity of airflow obstruction and body weight. Lung volume reduction surgery (LVRS) is a recent advance in the treatment of patients with severe emphysema that results in improved pulmonary function. We formed the hypothesis that improved lung mechanics after LVRS would result in body weight gain. DESIGN: Retrospective chart review. PATIENTS: All patients who underwent bilateral LVRS for severe emphysema at the University of Michigan between January 1995 and April 1996 were eligible for the study. MEASUREMENTS AND RESULTS: Pulmonary function and body weight were measured preoperatively and at 3, 6, and 12 months postoperatively for patients who underwent bilateral LVRS between January 1995 and April 1996. The average weight gain in 38 patients returning for 12 months of follow-up was 3.8 +/- 0.9 kg, or 6.2% of the preoperative weight. Women gained significantly more weight than men (9.2 vs 2.2%, respectively) at 1 year. Interestingly, there was no correlation between change in weight and postoperative change in FEV(1), FVC, residual volume (RV), total lung capacity (TLC), or RV/TLC at 12 months. However, there was a statistically significant correlation between weight gained and improvement in diffusion of carbon monoxide measured 12 months postoperatively. CONCLUSIONS: This study shows that patients with severe emphysema gain weight after LVRS. These changes were independent of changes in pulmonary mechanics but may be a result of improved gas exchange. These findings provide further information about benefits of LVRS in patients with advance emphysema that are beyond simple changes in pulmonary function.

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.

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.

Primary amyloidoma of the chest wall.

Primary amyloidoma of the chest wall presents as an aggressive tumor that causes local destruction. It is best treated with wide local excision and reconstruction as required, which usually is curative. A search for occult systemic disease also is recommended.

Biomechanical study of sternal closure using rigid fixation techniques in human cadavers.

BACKGROUND: We believe rigid plate fixation may be superior to wire fixation in sternal closure, as rigid fixation used in the craniofacial skeleton has shown greater stability, lower postoperative pain, and accelerated bone healing. We hypothesize that sterna fixed with titanium plates are more stable mechanically than sterna fixed with wires. METHODS: The sterna from human cadavers were used in this two-phased study. Phase I compared wires to four-hole titanium straight plates. Phase II compared wires to four-hole titanium custom H plates. The sterna were tested biomechanically using all fixation methods. RESULTS: Phase I showed no statistically significant difference in the stiffness or lateral displacement between the wired and straight plated sterna. Phase II showed a statistically significant greater stiffness (p < 0.05) and less lateral displacement (p < 0.05) in the custom plated sterna over the wired sterna. CONCLUSIONS: Our results showed that custom titanium H plates were superior to wire fixation. Furthermore, our results established the importance of plate configuration in sternal fixation. Our study may have beneficial clinical implications, as decreased motion at the sternotomy site could mean less postoperative pain, a decreased incidence of infection, and accelerated bone healing.

Shone's anomaly: operative results and late outcome.

Shone's anomaly, a congenital cardiac malformation, consists of multiple levels of left heart obstruction including supravalvar mitral ring, parachute mitral valve, subaortic stenosis, and coarctation. The prognosis for patients with Shone's anomaly is poor. To assess operative results and late outcome, we reviewed the records of 30 consecutive patients seen with Shone's anomaly at our institution between 1966 and 1989. Anatomical diagnoses in these patients were supravalvar mitral ring (22 patients), mitral valve abnormalities including parachute mitral valve, fused chordae, or single papillary muscle (26 patients), subaortic gradients (26 patients), and coarctation (29 patients). Nineteen patients had all four lesions. Other common defects were bicuspid aortic valve (19 patients) and ventricular septal defect (20). Two patients were treated medically. The other 28 patients required 84 operative procedures with 18 patients undergoing more than one procedure. Operations included coarctation repair (28 patients), mitral valve repair or replacement (11), ventricular septal defect closure (8), subaortic resection (8), and complex left ventricular outflow tract reconstruction or bypass (4). Age at first operation ranged from 7 days to 7 years (median age, 3 months). There were no operative deaths at the first operation. However, mortality rose to 24% (4/17) after the second operation. All operative deaths were secondary to severe mitral valve disease. The survivors have been followed from 1 to 16 years (mean follow-up, 6 +/- 1 years). There were no late or sudden deaths. Morbidity has included stroke (1), gastrointestinal bleeding (2), permanent heart block (1), and persistent congestive heart failure (6).(ABSTRACT TRUNCATED AT 250 WORDS)