David P. Mason

Should lung transplantation be performed for patients on mechanical respiratory support? The US experience

OBJECTIVE The study objectives were to (1) compare survival after lung transplantation in patients requiring pretransplant mechanical ventilation or extracorporeal membrane oxygenation with that of patients not requiring mechanical support and (2) identify risk factors for mortality. METHODS Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to January 2008. A total of 15,934 primary transplants were performed: 586 in patients on mechanical ventilation and 51 in patients on extracorporeal membrane oxygenation. Differences between nonsupport patients and those on mechanical ventilation or extracorporeal membrane oxygenation support were expressed as 2 propensity scores for use in comparing risk-adjusted survival. RESULTS Unadjusted survival at 1, 6, 12, and 24 months was 83%, 67%, 62%, and 57% for mechanical ventilation, respectively; 72%, 53%, 50%, and 45% for extracorporeal membrane oxygenation, respectively; and 93%, 85%, 79%, and 70% for unsupported patients, respectively (P < .0001). Recipients on mechanical ventilation were younger, had lower forced vital capacity, and had diagnoses other than emphysema. Recipients on extracorporeal membrane oxygenation were also younger, had higher body mass index, and had diagnoses other than cystic fibrosis/bronchiectasis. Once these variables, transplant year, and propensity for mechanical support were accounted for, survival remained worse after lung transplantation for patients on mechanical ventilation and extracorporeal membrane oxygenation. CONCLUSION Although survival after lung transplantation is markedly worse when preoperative mechanical support is necessary, it is not dismal. Thus, additional risk factors for mortality should be considered when selecting patients for lung transplantation to maximize survival. Reduced survival for this high-risk population raises the important issue of balancing maximal individual patient survival against benefit to the maximum number of patients.

Impact of Smoking Cessation Before Resection of Lung Cancer: A Society of Thoracic Surgeons General Thoracic Surgery Database Study

BACKGROUND Smoking cessation is presumed to be beneficial before resection of lung cancer. The effect of smoking cessation on outcome was investigated. METHODS From January 1999 to July 2007, in-hospital outcomes for 7990 primary resections for lung cancer in adults were reported to the Society of Thoracic Surgeons General Thoracic Surgery Database. Risk of hospital death and respiratory complications was assessed according to timing of smoking cessation, adjusted for clinical confounders. RESULTS Hospital mortality was 1.4% (n = 109), but 1.5% in patients who had smoked (105 of 6965) vs 0.39% in those who had not (4 of 1025). Compared with the latter, risk-adjusted odds ratios were 3.5 (p = 0.03), 4.6 (p = 0.03), 2.6 (p = 0.7), and 2.5 (p = 0.11) for those whose timing of smoking cessation was categorized as current smoker, quit from 14 days to 1 month, 1 to 12 months, or more than 12 months preoperatively, respectively. Prevalence of major pulmonary complications was 5.7% (456 of 7965) overall, but 6.2% in patients who had smoked (429 of 6941) vs 2.5%% in those who had not (27 of 1024). Compared with the latter, risk-adjusted odds ratios were 1.80 (p = 0.03), 1.62 (p = 0.14), 1.51 (p = 0.20), and 1.29 (p = 0.3) for those whose timing of smoking cessation was categorized as above. CONCLUSIONS Risks of hospital death and pulmonary complications after lung cancer resection were increased by smoking and mitigated slowly by preoperative cessation. No optimal interval of smoking cessation was identifiable. Patients should be counseled to stop smoking irrespective of surgical timing.

A Comparison of Two Stereotactic Body Radiation Fractionation Schedules for Medically Inoperable Stage I Non-small Cell Lung Cancer: The Cleveland Clinic Experience

Purpose: To assess the impact of fractionation upon tumor control and toxicity in medically inoperable early stage lung cancer patients treated with stereotactic body radiotherapy. Methods: We reviewed 94 consecutive stereotactic body radiotherapy treatments (86 patients) with medically inoperable stage I non-small cell lung cancer receiving either 50 Gy in five fractions (n = 56) or 60 Gy in three fractions (n = 38) from October 2003 to August 2007. Institutional practice was 10 Gy × 5 before March 1, 2006, when it changed to 20 Gy × 3 to conform to Radiation Therapy Oncology Group 0236 unless otherwise dictated clinically. Results: Median age was 73 years and median Karnofsky performance status 80. A total of 69 lesions were T1, 24 were T2 lung cancer. Median follow-up was 15.3 months. For the 50- and 60-Gy cohorts at 1 year, local control was 97.3% versus 100%, nodal failure 7.3% versus 3.4%, distant metastasis rate 21.8% versus 29.5%, and overall survival 83.1% versus 76.9% (p = 0.68, 0.54, 0.56, and 0.54, respectively). There was no difference in overall survival for patients with histologic (n = 61) compared with radiographic (n = 33) diagnosis. There was no impact of fractionation in the subset of T2 tumors. We observed two cases (2.2%) of clinical grade 2 pneumonitis. Mild late chest wall toxicity (grade 1 or 2) was seen in nine patients (10%) at a median of 8.4 months after treatment and was more common in the 60-Gy group (7 of 38 [18%] versus 2 of 56 [4%], p = 0.028). Conclusions: Local control, overall survival, nodal failure, and distant failure were not affected by fractionation. Chest wall toxicity was more common with 60-Gy group.

Should lung transplantation be performed using donation after cardiac death? The United States experience

OBJECTIVE We compared 1) survival after lung transplantation of recipients of donation after cardiac death (DCD) versus brain death donor organs in the United States and 2) recipient characteristics. METHODS Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to May 2007. Follow-up after DCD lung transplantation extended to 8.6 years, median 1 year. Differences among recipients of DCD versus brain death donor organs were expressed as a propensity score for use in comparing risk-adjusted survival. RESULTS A total of 14,939 transplants were performed, 36 with DCD organs (9 single, 27 double). Among the 36 patients, 3 have died after 1 day, 11 days, and 1.5 years. Unadjusted survival at 1, 6, 12, and 24 months was 94%, 94%, 94%, and 87%, respectively, for DCD donors versus 92%, 84%, 78%, and 69%, respectively, for brain death donors (P = .04). DCD recipients were more likely to undergo double lung transplantation and have diabetes, lower forced 1-second expiratory volume, and longer cold ischemic times. Once these were accounted for and propensity adjusted, survival was still better for DCD recipients, although the P value equals .06. CONCLUSION Concern about organ quality and ischemia-reperfusion injury has limited the application of lung DCD. However, DCD as practiced in the United States results in survival at least equivalent to that after brain death donation. It also demonstrates selection bias, particularly in performing double lung transplantation, making generalization regarding survival difficult. Nevertheless, the data support the expanded use of DCD.

Bridge to lung transplantation using short-term ambulatory extracorporeal membrane oxygenation

Severe respiratory failure refractory to mechanical ventilation can occur in patients awaiting lung transplantation (LTx). Use of extracorporeal membrane oxygen (ECMO) to bridge these patients to LTx is associated with considerable morbidity and mortality. Most techniques rely on femoral cannulation, thereby immobilizing patients. This in turn can lead to rapid deconditioning and predisposes patients to nosocomial pneumonia, deep venous thrombosis, and muscle wasting. This case highlights the use of upper-extremity ECMO, which was established without intubation in a critically ill transplant candidate, allowed ambulation, and ultimately served as a successful bridge to LTx.

Guidelines for Donor Lung Selection: Time for Revision?

BACKGROUND Few data support current guidelines for donor selection in lung transplantation. We determined degree of compliance with current donor guidelines, effect of these and variances on survival, and other donor factors predicting survival. METHODS From July 1999 to June 2008, 10,333 primary transplants were performed in the US, with United Network for Organ Sharing data available for age, ABO type, chest radiograph, arterial difference in partial pressure of oxygen (PaO(2)) greater than 300 on 100% fraction of inspired oxygen, smoking, absence of aspiration/sepsis, and purulent secretions. Multivariable survival methods were used to determine relevance of these and new variables, adjusted for recipient risk factors. RESULTS In 56% of transplants, variance from at least one guideline was observed: chest radiograph, 41%; smoking, 21%; and PaO(2), 18%; but rarely ABO compatibility (0.06%). Practice within guidelines was not associated with increased mortality. Common variances from guidelines; eg, PaO(2)/fraction of inspired oxygen down to 230, were not associated with increased mortality, but smoking (p = 0.02) was. New donor variables associated with increased mortality were diabetes (p = 0.001), presence of cytomegalovirus antibodies (p < 0.0001), recent smoking history (p = 0.02), African-American (p = 0.005), blood type A (p = 0.02), death other than from head trauma (p = 0.02), and gender (p = 0.02), race (p = 0.03), and size (p = 0.002) discordances. CONCLUSIONS Variance from current donor guidelines for lung transplantation is frequent; analysis suggests that donor PaO(2) ranges can be widened and a suspicious chest radiograph, evidence of sepsis, and purulent bronchial secretions ignored. Older age and smoking history appear to have a minor impact. New and possibly important factors identified suggest the need to better understand the impact of a wider range of donor variables on recipient outcomes.

Early Experience With Lung Transplantation Using Donors After Cardiac Death

Lung transplantations that utilize donor organs after cardiac death (DCD) can substantially increase the number of available allografts for waiting recipients. Unfortunately, reported clinical outcomes are limited and widespread acceptance is slow. To further examine the potential of this modality, the results of 4 patients transplanted with DCD organs, implementing a protocol of controlled organ retrieval (Maastricht Classification III), were reviewed. There were no operative deaths; extracorporeal membrane oxygenation was required in 1 patient secondary to severe primary graft dysfunction. Three patients are alive and well at 4, 15 and 21 months; 1 patient died at 34 months with bronchiolitis obliterans syndrome, in part attributable to medication non-compliance.

A critical evaluation of a percutaneous diagnostic and treatment strategy for chylothorax after thoracic surgery

OBJECTIVE Because chylothorax complicating thoracic surgery is difficult to diagnose and failure of nonoperative management necessitates further surgery, we critically evaluated an evolving percutaneous strategy for diagnosing and treating chylothorax. METHODS After thoracic surgery, 37 patients with a clinical diagnosis of chylothorax were referred for lymphangiography for definitive diagnosis and percutaneous treatment. Successful localization of the cisterna chyli by lymphangiogram facilitated percutaneous cannulation of the thoracic duct and its embolization. In patients in whom cannulation was not possible, the thoracic duct was percutaneously disrupted. RESULTS DIAGNOSIS Lymphangiography was successful in 36 of the 37 patients (97%). Contrast extravasation, confirming clinical diagnosis, was present in 21 of the 36 (58%). MANAGEMENT Twenty-one of 36 patients underwent 22 lymphangiographically directed percutaneous interventions: 12 embolizations and 10 disruptions. Mortality was zero, with two manageable complications. Patients without percutaneous intervention were discharged a median of 7 days (range 4-58) after first lymphangiography, 8 days (range 2-19) after percutaneous embolization, and 19 days (range 6-48) after first disruption. Eight patients had nine subsequent reoperations for chylothorax, two with negative lymphangiograms; no embolization patient required reoperation. CONCLUSIONS There is a discrepancy between the clinical diagnosis of chylothorax after thoracic surgery and the presumed gold standard of diagnosis, contrast extravasation at lymphangiogram. Percutaneous treatment by thoracic duct embolization or disruption is safe and may obviate reoperation, but embolization of the thoracic duct is preferable to its disruption.

International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report

BACKGROUND The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD). METHODS In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation. RESULTS There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category III, whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant [NS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11). CONCLUSION This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant.

A Phase II Study of Perioperative Concurrent Chemotherapy, Gefitinib, and Hyperfractionated Radiation Followed by Maintenance Gefitinib in Locoregionally Advanced Esophagus and Gastroesophageal Junction Cancer

Background: Concurrent chemoradiotherapy (CCRT) for locoregionally advanced esophageal or gastroesophageal junction cancer produces high locoregional control rates but suboptimal distant metastatic control (DMC) and overall survival. This phase II study added gefitinib (G) to our previously tested CCRT regimen in an effort to improve these outcomes. Methods: Eligibility required T3, N1, or M1a esophageal or gastroesophageal junction squamous cell or adenocarcinoma staged by esophageal ultrasound and positron emission tomography/computed tomography. Four-day continuous intravenous infusions of cisplatin (20 mg/m2/d) and fluorouracil (1000 mg/m2/d) began on day 1 of preoperative radiation (30 Gy and 1.5 Gy bid). Surgery followed in 4 to 6 weeks, and an identical course of CCRT 6 to 10 weeks postoperatively. G 250 mg/d was given with preoperative CCRT for 4 weeks and restarted with postoperative therapy for 2 years. Results were retrospectively compared with our historical series of 93 patients given CCRT without G. Results: Between April 2003 and July 2006, 80 patients were enrolled. Patient and tumor characteristics were similar to our historical series. G did not increase toxicity except for development of rash in 42 (53%) and diarrhea in 44 (55%) 3-year Kaplan-Meier estimates (G versus non-G treated patients) included: overall survival (42% versus 28%, p = 0.06), DMC (40% versus 32%, p = 0.33), and locoregional control (76% versus 77%, p = 0.74). Intolerance for G maintenance occurred in 48% of patients. Patients who experienced G related diarrhea appeared to have improved outcomes. Conclusions: Although G did not worsen CCRT toxicity, maintenance therapy proved difficult. This contemporary cohort of patients enjoyed superior survival, which does not solely reflect a decrease in DMC and merits further investigation.