Robbin G. Cohen

Living-donor lobar lung transplantation experience: Intermediate results

OBJECTIVE Living-donor lobar lung transplantation offers an alternative for patients with a life expectancy of less than a few months. We report on our intermediate results with respect to recipient survival, complications, pulmonary function, and hemodynamic reserve. METHODS Thirty-eight living-donor lobar lung transplants were performed in 27 adult and 10 pediatric patients for cystic fibrosis (32), pulmonary hypertension (two), pulmonary fibrosis (one), viral bronchiolitis (one), bronchopulmonary dysplasia (one), and posttransplantation obliterative bronchiolitis (one). Seventy-six donors underwent donor lobectomies. RESULTS There were 14 deaths among the 37 patients, with an average follow-up of 14 months. Predominant cause of death was infection, consistent with the large percentage of patients with cystic fibrosis in our population. The overall incidence of rejection was 0.07 episodes/patient-month, representing 0.8 episodes/patient. Postoperative pulmonary function testing generally showed a steady improvement that plateaued by postoperative months 9 to 12. Fourteen patients who were followed up for at least 1 year underwent right heart catheterization; pressures and pulmonary vascular resistances were within normal ranges. Bronchiolitis obliterans was definitively diagnosed in three patients. Among the 76 donors, complications in the postoperative period included postpericardiotomy syndrome (three), atrial fibrillation (one), and surgical reexploration (three). CONCLUSIONS We believe that these data support an expanded role for living-donor lobar lung transplantation. Our intermediate data are encouraging with respect to the functional outcome and survival of these critically ill patients, who would have died without this option.

Lobar transplantation: Indications, technique, and outcome

Lobar transplantation represents a therapeutic option for children and some adults with severe end-stage pulmonary disease. Six patients including two neonates, three children, and one adult underwent lobar transplantation. Ages ranged from 17 days to 21 years. Transplant procedures were unilateral in the neonates and two of the children and bilateral in the child and adult who had cystic fibrosis. The donor lobes were from cadavers in the two neonates and living related donors in the children and the adult. Unilateral grafts involved use of the right upper lobe in the 12-year-old patient with bronchopulmonary dysplasia; right middle lobe with a ventricular septal defect repair in the 4-year-old patient with Eisenmengers syndrome, left upper lobe in the 28-day-old patient with primary pulmonary hypertension, and the right upper and middle lobes in the 17-day-old patient with diaphragmatic hernia. Bilateral lobar transplantations were performed with the right lower and left lower lobes in the two patients with cystic fibrosis (aged 13 and 21 years). The two neonates underwent emergency transplantation with the use of extracorporeal membrane oxygenation as a bridge. Perioperative survival was 83%, with only the 4-year-old patient with ventricular septal defect/Eisenmengers syndrome dying early. No airway complications were observed. The unilateral grafts received most of the blood flow as shown by perfusion scanning (range 74% to 99%). Living related donor complications included prolonged air leaks (> 6 days) in two patients. In urgent situations, such as an infant requiring extracorporeal membrane oxygenation, and in the existing milieu of donor shortage, lobar transplantation (living related or cadaveric) is a surgically feasible procedure and can provide a donor source in the limited time frame of these clinical situations. Bilateral lobe transplantation may be a viable option for patients with cystic fibrosis and life-threatening respiratory decompensation.

Living-related donor iobectomy for bilateral lobar transplantation in patients with cystic fibrosis

Donor lobectomy has been performed in 14 patients enabling 7 recipients with cystic fibrosis to undergo bilateral living-related lobar pulmonary transplantation. Donors included 11 patients, 2 brothers, and 1 uncle. Donor mean age was 43 years (range 24 to 55 years). Their mean height and weight was 170 cm (range, 169 to 180 cm) and 72.4 kg (range, 55 to 90 kg), respectively, compared with 161 cm (range, 140 to 175 cm) and 42.4 kg (range, 27 to 55 kg), respectively, in the recipient group. Donor pulmonary evaluation consisted of a history and physical examination, chest roentgenogram and computed tomographic scan, spirometry with arterial blood gas measurement, echocardiography, and perfusion scanning. From each pair of donors, one was selected for right lower lobectomy and the other for left lower lobectomy. Standard lobectomy techniques were modified to facilitate implantation and optimize preservation of the donor lobes. On the right side, the middle lobe was removed and discarded in the first three donors to provide an adequate cuff of pulmonary artery and bronchus for implantation. With increased experience, this has proved not to be necessary. There have been no deaths and no long-term complications in the donor group. Prolonged postoperative air leaks occurred in the 3 patients who underwent right lower and middle lobectomies. All donors have been able to resume their previous lifestyles. Living-related donor lobectomy provides an alternative to cadaveric organs in select patients in need of pulmonary transplantation.

Experience with living-donor lobar transplantation for indications other than cystic fibrosis.

OBJECTIVE Since development of a living donor bilateral lobar transplantation protocol for patients with cystic fibrosis, our indications have expanded to include recipients with other diagnoses. METHODS We report on our experience in eight patients with primary pulmonary hypertension, postchemotherapy pulmonary fibrosis, bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and obliterative bronchiolitis. The average age of the eight patients was 19.1 years (range 9 to 40). The mean preoperative carbon dioxide tension for the four patients who did not have primary pulmonary hypertension was 92 mm Hg (range 64 to 120 mm Hg), and the two patients with pulmonary fibrosis were intubated (one on high-frequency jet ventilation). Each recipient received a right lower lobe (n = 7) or middle lobe (n = 1) and a left lower lobe (n = 8) from a total of 16 donors representing various combinations of the recipients family (n = 15) and an unrelated friend (n = 1). RESULTS With an average follow-up of 1 year the overall survival is 75%. For the five patients followed up for at least 1 year, mean forced vital capacity was 80.6%, forced expiratory volume in 1 second was 75.6%, mid-forced expiratory flow was 64%, and diffusing lung capacity corrected for alveolar volume was 73% of predicted. For those patients with primary pulmonary hypertension, preoperative hemodynamics revealed mean pressures as follows: blood pressure 84.8 mm Hg, right atrial pressure 7.8 mm Hg, pulmonary artery pressure 71.3 mm Hg, pulmonary capillary wedge pressure 9.5 mm Hg, cardiac index 2.9 L/min per square meter, and pulmonary vascular resistance index 22.8 Wood units. Postoperative hemodynamics revealed a mean blood pressure of 84.3 mm Hg, right atrial pressure of 2.7 mm Hg, pulmonary artery pressure of 16 mm Hg, pulmonary capillary wedge pressure of 7.3 mm Hg, cardiac index of 4.2 L/min per square meter, and pulmonary vascular resistance index of 1.9 Wood units. CONCLUSIONS Early results of living-donor bilateral lobar transplantation for diseases other than cystic fibrosis have resulted in satisfactory survival and pulmonary function. Additionally, patients with severe primary pulmonary hypertension have had dramatic normalization of their hemodynamics despite the limited amount of lung tissue transplanted. We believe that the data from this small cohort experience compares favorably with our larger series with cystic fibrosis and supports an expanded role for living-donor lobar transplantation in patients with alternate indications.

Occult Metastases in Lymph Nodes Predict Survival in Resectable Non–Small-Cell Lung Cancer: Report of the ACOSOG Z0040 Trial

PURPOSE The survival of patients with non-small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. PATIENTS AND METHODS Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. RESULTS From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). CONCLUSION In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.

Living Donor Lung Transplantation

Since 1993 a total of 101 living-donor bilateral lung transplants have been performed with acceptable results when compared with those utilizing cadaveric lung grafts. Though most recipients were patients with cystic fibrosis who were rapidly deteriorating, the indications for livedonor lung transplantation have been expanded to include some cystic fibrosis patients in a more elective setting, as well as select patients with other end-stage pulmonary diseases. One-year Kaplan-Meier recipient survival is 72%. Seventy-six percent of deaths occur within the first 2 months after transplantation. The most common cause of death is infection, which accounts for 62% of the 1-year mortality rate. The incidence of rejection is 0.8 episodes per patient. Thirty percent of rejection episodes are unilateral, and most tend to be mild. Altogether, 203 patients have undergone donor lobectomy, with a mean age of 37 ± 12 years (range 18–56 years). Operations included left lower lobectomy (102 patents), right lower lobectomy (97 patients), and right middle and lower lobectomy (4 patients). There has been no donor mortality. Postoperative Rand 36 Question Quality of Life scores, rating physical function, social functioning, and role limitation due to physical and emotional health, are well over 92 (of a possible score of 100). Eighty-five percent of donors said that their health was no different or improved since donation.

Arch and visceral/renal debranching combined with endovascular repair for thoracic and thoracoabdominal aortic aneurysms

OBJECTIVE We report a single-center experience using the hybrid procedure, consisting of open debranching, followed by endovascular aortic repair, for treatment of arch/proximal descending thoracic/thoracoabdominal aortic aneurysms (TAAA). METHODS From 2005 to 2010, 51 patients (33 men; mean age, 70 years) underwent a hybrid procedure for arch/proximal descending thoracic/TAAA. The 30-day and in-hospital morbidity and mortality rates, and late endoleak, graft patency, and survival were analyzed. Graft patency was assessed by computed tomography, angiography, or duplex ultrasound imaging. RESULTS Hybrid procedures were used to treat 27 thoracic (16 arch, 11 proximal descending thoracic) and 24 TAAA (Crawford/Safi types I to III: 3; type IV: 12; type V: 9). The hybrid procedure involved debranching 47 arch vessels or 77 visceral/renal vessels using bypass grafts, followed by endovascular repair. Seventy-five percent of debranching and endovascular repair procedures were staged, with an average interval of 28 days. Major 30-day and in-hospital complications occurred in 39% of patients and included bypass graft occlusion in four, endoleak reintervention in two, and paraplegia in one. Mortality was 3.9%. During a mean follow-up of 13 months, three additional type II endoleaks required intervention, and one bypass graft occluded. No aneurysm rupture occurred during follow-up. Primary bypass graft patency was 95.3%. Actuarial survival was 86% at 1 year and 67% at 3 years. CONCLUSION The hybrid procedure is associated with acceptable rates of mortality and paraplegia when used for treatment of arch/proximal descending thoracic/TAAA. These results support this procedure as a reasonable approach to a difficult surgical problem; however, longer follow-up is required to appraise its ultimate clinical utility.

Regional topical hypothermia of the beating heart: preservation of function and tissue

BACKGROUND Protection of the myocardium during beating heart operations is paramount. The goal of this study is to determine if regional topical hypothermia (RTH) preserves myocardial viability and function during periods of temporary coronary artery occlusion. METHODS Sixteen pigs were divided into two groups (RTH and control). Each group received 40 minutes of midleft anterior descending coronary occlusion followed by 3 hours of reperfusion. The RTH group (n = 10) received RTH and the control group (n = 6) received no cooling. Myocardial and core temperatures were measured with thermistors. Sonomicrometers and micromonameters were used to determine load independent indices of myocardial function. These indices were measured at base line, during coronary occlusion, and at 3 hours of reperfusion. The myocardium at risk and the infarct area were determined with monastral blue dye and triphenyl tetrazolium chloride staining. RESULTS The mean myocardial temperature in the risk zone during coronary occlusion was significantly less in the RTH group (29.4 degrees C +/- 5.6 degrees C versus 35.7 degrees C +/- 1.1 degrees C, p < 0.05). After 40 minutes of coronary occlusion, both the RTH group and control had a significant reduction in regional elastance (9.38 +/- 3.54 and 11.05 +/- 1.67 mm Hg/mm) compared with base line measurements (14.70 +/- 2.42 and 16.80 +/- 4.79 mm Hg/mm), p < 0.05. However, after 3 hours of reperfusion, the elastance returned to base line levels in the RTH group (15.83 +/- 3.06 mm Hg/mm) but remained significantly depressed in the control group (9.97 +/- 3.63 mm Hg/mm, p < 0.04). Myocardial necrosis as a percentage of the risk zone was significantly less in the hypothermia group (25% +/- 2% versus 62% +/- 5%, p < 0.001). CONCLUSIONS Regional topical hypothermia during isolated temporary coronary occlusion provides regional myocardial protection expressed as a return of function and decreased necrosis. Regional topical hypothermia may be clinically applicable to myocardial preservation during beating heart operations.

Talc pleurodesis: Talc slurry versus thoracoscopic talc insufflation in a porcine model

BACKGROUND Pleurodesis using both talc slurry and thoracoscopic talc insufflation has been shown to be clinically effective. This study compares these two modalities of pleural talc instillation in an animal model. METHODS Eleven immature pigs underwent general endotracheal anesthesia. On one side, a slurry of 5 g sterile United States Pharmacopeia talc in 50 mL of saline solution was instilled through a thoracostomy tube. On the other side, the lung was deflated and 5 g of dry talc was insufflated under thoracoscopic visualization. The animals were sacrificed 30 days later, and the quality of pleural adhesions was graded from 0 to 2 (0 = absent; 1 = light; 2 = dense) in each of six regions of each hemithorax. The distribution of adhesions on each side was graded from 0 to 6, according to the number of areas that contained adhesions. RESULTS One animal died of anesthetic complications. Among the survivors, adhesions produced by both methods were dense and diffuse in 8 of 10 animals, and light and diffuse in 1 animal. One animal had light or absent adhesions on the talc slurry side, and dense and diffuse adhesions on the thoracoscopic talc insufflation side. There was no difference between the techniques for density of adhesion scores (talc slurry, 9.9 +/- 2.2; thoracoscopic talc insufflation, 10.0 +/- 2.5) or distribution of adhesion scores (talc slurry, 5.5 +/- 1.0; thoracoscopic talc insufflation, 5.8 +/- 0.4) (p > 0.1). CONCLUSIONS Effective pleurodesis in a porcine model can be obtained with either talc slurry or thoracoscopic talc insufflation.

A comparison of aortic valve replacement via an anterior right minithoracotomy with standard sternotomy: a propensity score analysis of 492 patients

OBJECTIVES Right anterior minithoracotomy with central arterial cannulation is our preferred technique of minimally invasive aortic valve replacement (AVR). We compared perioperative outcomes with this technique to those via sternotomy. METHODS Between March 1999 and December 2013, 492 patients underwent isolated AVR via either sternotomy (SAVR, n = 198) or minimally invasive right anterior thoracotomy (MIAVR, n = 294) in our institution. Univariate comparisons between groups were made to evaluate overall outcomes and adverse events. To control treatment selection bias, propensity scores were constructed from core patient characteristics. A propensity score-stratified analysis of outcome and adverse events was then performed. RESULTS Overall mortality was 2.5 and 1.0% in the SAVR and MIAVR groups, respectively. Hospital and ICU stays were shorter, there was less intraoperative blood product usage, and fewer wound infections in the MIAVR group. There were no differences in other adverse events, including strokes. The composite end-point of alive and adverse event-free was significantly more common in the MIAVR group (83 vs 74%, P = 0.002). After adjusting for the propensity score, hospital and ICU stays remained shorter and intraoperative blood product usage remained less in the MIAVR group. There was no difference in mortality, stroke or other adverse events between groups. CONCLUSION Minimally invasive AVR via an anterior right thoracotomy with predominately central cannulation can be performed with morbidity and mortality similar to that of a sternotomy approach. There appear to be advantages to this minimally invasive approach when compared with sternotomy in terms of less intraoperative blood product usage, lower wound infection rates and decreased hospital stays. If mortality and the occurrence of adverse events are taken together, MIAVR may be associated with better outcomes. As minimally invasive AVR becomes more common, further long-term follow-up is needed and a prospective multicentre randomized trial would be warranted.