Michael R. Mill

Improved results of lung transplantation for patients with cystic fibrosis

Patients with cystic fibrosis pose particular challenges for lung transplant surgeons. Earlier reports from North American centers suggested that patients with cystic fibrosis were at greater risk for heart-lung or isolated lung transplantation than other patients with end-stage pulmonary disease. During a 3 1/2 year period, 44 patients with end-stage lung disease resulting from cystic fibrosis underwent double lung transplantation at this institution. During the same interval, 18 patients with cystic fibrosis died while waiting for lung transplantation. The ages of the recipients ranged from 8 to 45 years, and mean forced expiratory volume in 1 second was 21% predicted. Seven patients had Pseudomonas cepacia bacteria before transplantation. Bilateral sequential implantation with omentopexy was used in all patients. There were no operative deaths, although two patients required urgent retransplantation because of graft failure. Cardiopulmonary bypass was necessary in six procedures in five patients and was associated with an increased blood transfusion requirement, longer postoperative ventilation, and longer hospital stay. Actuarial survival was 85% at 1 year and 67% at 2 years. Infection was the most common cause of death within 6 months of transplantation (Pseudomonas cepacia pneumonia was the cause of death in two patients), and bronchiolitis obliterans was the most common cause of death after 6 months. Actuarial freedom from development of clinically significant bronchiolitis obliterans was 59% at 2 years. Results of pulmonary function tests improved substantially in survivors, with forced expiratory volume in 1 second averaging 78% predicted 2 years after transplantation. Double lung transplantation can be accomplished with acceptable morbidity and mortality in patients with cystic fibrosis.

Long term results of lung transplantation for cystic fibrosis.

OBJECTIVES We reviewed our experience with lung transplant for cystic fibrosis (CF) over a 10-year period to identify factors influencing long-term survival. METHODS One hundred and twenty-three patients with CF have undergone 131 lung transplant procedures at our institution; 114 have had bilateral sequential lung transplants (DLTX) and nine have had bilateral lower lobe transplants from living donors. Three patients had retransplant for acute graft failure, and five had late retransplant for bronchiolitis obliterans syndrome (BOS). Kaplan-Meier survival was calculated for the entire cohort and for subsets at higher risk of death to determine factors predicting a better outcome. RESULTS Actuarial survival for the entire group of DLTX CF patients was 81% at 1 year, 59% at 5 years, and 38% at 10 years. Lobar transplant was associated with a poorer survival (37.5% at 1 and 5 years). Among DLTX patients, colonization with Burkholderia cepacia was present in 22 patients and was associated with poorer outcome (1- and 5-year survival 60 and 36% in B. cepacia patients vs. 86 and 64% in non-cepacia patients). DLTX patients younger than age 20 (n=22) had a similar survival to patients age 20 or older (n=90). Being on a ventilator at the time of transplant was not associated with poorer survival (n=8). BOS affects increasing numbers of survivors with time. Five CF patients have been retransplanted due to BOS with one operative death and 1-year survival of 60%. CONCLUSIONS DLTX has acceptable long term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but transplantation is still warranted.

Anatomically sound, simplified approach to repair of “complete” atrioventricular septal defect

BACKGROUND There are few congenital anomalies of the heart that have benefited more from thorough anatomic analysis than the complex anomaly known as atrioventricular septal defect in the setting of common atrioventricular junction. Recent advances in understanding the anatomy of this lesion have led to alternative methods of repairing these defects. METHODS The medical records of 21 consecutive patients undergoing repair of complete atrioventricular septal defect have been reviewed. Nine of these patients had a standard one- or two-patch repair, and 12 had direct closure of the ventricular element of the defect. RESULTS Direct closure resulted in significantly shorter pump and cross-clamp times. Follow-up for an average of 34 months suggests that when direct closure can be performed, the results are comparable with those of the more standard technique. CONCLUSIONS Our initial success with this approach is encouraging; however, longer follow-up is required to establish whether it will be broadly applicable.

Isolated lung transplantation for end-stage lung disease: A viable therapy

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred consecutive thymectomies for myasthenia gravis

BACKGROUND Between June 1997 and November 1993, 100 consecutive thymectomies for myasthenia gravis were performed at University of North Carolina Hospitals in Chapel Hill. METHODS A consistent, planned protocol involving preoperative, intraoperative, and postoperative care was followed. All thymectomies were performed through a median sternotomy with removal of all visible thymus and perithymic fat in the anterior mediastinum. RESULTS There was no perioperative mortality or longterm morbidity. Mean postoperative hospital stay was 6.3 days (range, 3 to 18 days). Ninety-six percent of the patients were extubated the day of the operation, and all patients were extubated within 24 hours. Mean postoperative intensive care unit stay was 1.2 days (range, 1 to 4 days). After a mean follow-up of 65 months (range, 1 to 199 months), 78% of all patients are improved by at least one modified Osserman classification when their current status is compared with their worst preoperative disease severity. In fact, 69% of patients with mild disease preoperatively (class I, II, or III maximal severity) are in pharmacologic remission (asymptomatic without regular medication), whereas 29% of patients with severe disease (class IV or V) are in remission (p = 0.0001). CONCLUSIONS Our programmatic approach to thymectomy through a sternotomy has shown minimal morbidity and mortality. It is beneficial to myasthenics at both ends of the age and severity spectrum.

Lung Transplantation After Previous Thoracic Surgical Procedures

BACKGROUND This study examined results of lung transplantation after previous thoracic surgical procedures. METHODS Twenty percent of the 69 isolated lung transplantations performed at the University of North Carolina between January 1990 and June 1993 were in patients who had undergone a previous thoracic surgical procedure, and an additional 10% had undergone a previous chest tube placement. RESULTS No statistically significant increase in morbidity or mortality was observed between those having undergone a previous procedure or chest tube placement and all other patients. Specifically, the length of intubation, length of hospital stay, hospital mortality, or the number of patients who experienced major early complications was not significantly different between these groups. A statistically significant increase in the number of blood products used was observed in the patients with previous thoracic surgical procedures but not with patient having had previous chest tube placements. However, when the data were reanalyzed with respect to the use of cardiopulmonary bypass, those patients requiring bypass had a markedly poorer outcome that reached statistical significance in all of the parameters studied: hospital death, incidence of major complications, length of intubation, hospital stay, incidence of bleeding, and number of blood products used. CONCLUSIONS We conclude that although increased bleeding may be encountered, lung transplantation can be performed successfully in patients who have had previous thoracic surgical procedures without increased major morbidity or mortality; however, the use of cardiopulmonary bypass has been associated with significantly increased morbidity and mortality in our patient population.

Lung transplantation for cystic fibrosis: effective and durable therapy in a high-risk group

BACKGROUND The purpose of this study was to review our experience with lung transplantation in patients with end-stage cystic fibrosis. METHODS Eight-two patients with cystic fibrosis have undergone bilateral lung transplantation (n=76) or bilateral lower lobe transplantation (n=6) since October 1990. RESULTS Actuarial survival for the entire cohort is 79% at 1 year and 57% at 5 years. The development of bronchiolitis obliterans syndrome is the leading cause of death after the first year. Freedom from bronchiolitis obliterans syndrome is 84% at 1 year and 51% at 3 years. Pulmonary function tests improve dramatically in recipients. There was no association between death within 1 year and recipient age, weight, graft ischemic time, cytomegalovirus seronegativity, or the presence of pan-resistant organisms. Similarly, there was no association between the development of bronchiolitis obliterans syndrome within 2 years and ischemic time, number of rejection episodes, cytomegalovirus seronegativity, or the presence of panresistant organisms. CONCLUSIONS Despite their poor nutritional status and the presence of multiply resistant organisms, patients with cystic fibrosis can undergo bilateral lung transplantation with acceptable morbidity and mortality.

Anomalous course of the left brachiocephalic vein

An anomalous course of the left brachiocephalic vein beneath the aortic arch was identified in 7 patients undergoing surgical repair of congenital cardiac malformations. Six of these patients had the morphologic features of tetralogy of Fallot including severe obstruction to the right ventricular outflow tract and a right aortic arch. A review of the literature reveals this to be an uncommon anomaly. When it is present, however, it is frequently associated with a ventricular septal defect, obstruction of the right ventricular outflow, and aortic arch anomalies. This anomaly can be documented by echocardiography, at cardiac catheterization, or intraoperatively. The presence of a subaortic left brachiocephalic vein may have implications for the conduct of surgical procedures, especially in the setting of tetralogy of Fallot.

Determination of salivary digoxin with a dry strip immunometric assay

Analysis of salivary digoxin using a rapid dry chemistry, enzyme-labeled immunometric assay (ELIA) was compared with fluorescence polarization immunoassay (FPIA). Saliva and serum samples were obtained from 40 hospitalized patients who were taking digoxin chronically and from 8 patients just prior to treatment with digoxin. Unstimulated saliva samples were collected from 20 patients; however, saliva volumes from 10 pediatric patients were inadequate to permit analysis by FPIA, and 1 other had unmeasurable concentrations by both methods. Stimulated saliva was collected by having patients chew a small piece of Parafilm for 1–2 min. Salivary digoxin was analyzed using the same procedure recommended for serum digoxin by each manufacturer. There were no significant differences found between ELIA and FPIA determinations of unstimulated or stimulated salivary digoxin, serum digoxin, or saliva/serum concentration ratios. The saliva/serum ratio of the unstimulated group was approximately twice that of the stimulated group (p < 0.01) by both methods, suggesting that salivary digoxin concentration decreases with increased saliva production rate. Excellent correlations were found between ELIA and FPIA salivary digoxin concentrations and between stimulated saliva and serum concentrations by both assays. Weaker correlations were observed between unstimulated saliva and serum concentrations. There was no evidence of assay interference with either method in eight non-digitalized patients, each taking an average of 6.5 medications. The ELIA appears to provide equivalent results compared with the FPIA for the determination of salivary digoxin concentration. Further investigations are needed before salivary digoxin concentration monitoring can be recommended as an acceptable alternative to serum monitoring.

Single lung transplantation for eosinophilic granulomatosis

A 26-year-old woman with end-stage lung disease due to eosinophilic granulomatosis had single right lung transplantation with an excellent function result that persists beyond 9 months of follow-up. Single lung transplantation offers excellent palliation to selected patients with end-stage lung disease.