Outcomes with alemtuzumab induction therapy in lung transplantation: a comprehensive large-scale single-center analysis.

Alemtuzumab is a monoclonal antibody targeting CD52, increasingly used as induction therapy after transplantation. The aim of this study was to analyze the outcomes of alemtuzumab induction therapy followed by a low-dose maintenance immunosuppression in a large single-center cohort of lung transplant recipients. All patients, who received alemtuzumab induction followed by a low-dose maintenance immunosuppression were included in the analysis. Short- and long-term outcomes were analyzed. 721 lung transplant recipients, transplanted between January 2008 and June 2019, were included in this retrospective study. Freedom from higher-grade ACR at 1, 5, and 10 years was 98%, 96%, and 96%, respectively. Thirty-nine patients (5%) developed clinical AMR. Twenty-one percent of patients developed high-grade CKD. A total of 1488 infections were recorded. Sixteen percent were diagnosed within the first 3 months. Sixty-two patients (9%) developed a malignancy during follow-up. Freedom from CLAD at 1, 5, and 10 years was 94%, 72%, and 53%, respectively. Overall survival rates at 1, 5, and 10 years were 85%, 71%, and 61%, respectively. Alemtuzumab induction combined with a low-dose tacrolimus protocol is safe and associated with low rates of acute and chronic rejection, as well as an excellent long-term survival.

Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

OBJECTIVES: Lung transplantation for idiopathic pulmonary arterial hypertension has the highest reported postoperative mortality of all indications. Reasons lie in the complexity of treatment of these patients and the frequent occurrence of postoperative left ventricular failure. Transplantation on intraoperative extracorporeal membrane oxygenation support instead of cardiopulmonary bypass and even more the prolongation of extracorporeal membrane oxygenation into the postoperative period helps to overcome these problems. We reviewed our experience with this concept. METHODS: All patients undergoing bilateral lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative extracorporeal membrane oxygenation with or without prophylactic extracorporeal membrane oxygenation prolongation into the postoperative period between January 2000 and December 2014 were retrospectively analysed. RESULTS: Forty-one patients entered the study. Venoarterial extracorporeal membrane oxygenation support was prolonged into the postoperative period for a median of 2.5 days (range 1-40). Ninety-day, 1-, 3- and 5-year survival rates for the patient collective were 92.7%, 90.2%, 87.4% and 87.4%, respectively. When compared with 31 patients with idiopathic pulmonary arterial hypertension transplanted in the same period of time without prolongation of extracorporeal membrane oxygenation into the postoperative period, the results compared favourably (83.9%, 77.4%, 77.4%, and 77.4%; P = 0.189). Furthermore, these results are among the best results ever reported for this particularly difficult patient population. CONCLUSIONS: Bilateral lung transplantation for idiopathic pulmonary arterial hypertension with intraoperative venoarterial extracorporeal membrane oxygenation support seems to provide superior outcome compared with the results reported about the use of cardiopulmonary bypass. Prophylactic prolongation of venoarterial extracorporeal membrane oxygenation into the early postoperative period provides stable postoperative conditions and seems to further improve the results.

Thymomas and thymic carcinomas: prognostic factors and multimodal management.

BACKGROUND: Thymomas and thymic carcinomas are rare malignant tumors. We report the experience with the resection and multimodal treatment at a single department in Central Europe in the years 2001 to 2010. OBJECTIVE: We sought to determine prognostic factors in this patient population. METHODS: A 10-year retrospective analysis of 84 resections on 72 patients for thymomas/thymic carcinomas or their recurrences was performed. RESULTS: Patients admitted to a single thoracic surgery center presented with Masaoka-Koga stage I (29.2%), II (43.1%), III (13.9%), and IV (13.9%). In approximately 88.9% of cases, a complete resection could be reached. Using overall survival as an outcome measure, the 5-year survival rate was 87%. Of all the cases presented, 9.7% cases showed tumor recurrence and 6.9% cases showed tumor progression. There was decreased survival rate with increasing Masaoka-Koga stage (p = 0.017) and incomplete resection (p < 0.001). CONCLUSION: Completeness of resection and Masaoka-Koga stage were significant prognostic factors. Multidisciplinary treatments of patients with thymoma or thymic carcinoma result in good patient care, and global efforts with larger number of patients are needed to elucidate more about the biology, diagnosis, and treatment of these tumors.

Bronchial stump coverage with a pedicled pericardial flap: an effective method for prevention of postpneumonectomy bronchopleural fistula.

BACKGROUND: Bronchopleural fistula is a serious complication after pneumonectomy. The aim of this retrospective study was to investigate the efficacy of bronchial stump reinforcement with a pedicled flap of whole pericardium. METHODS: The bronchial stump of 93 consecutive patients who underwent pneumonectomy between July 1988 and March 2003 was covered with a pedicled pericardial flap. Pneumonectomy was performed for primary lung cancer in 89.2% of patients. The study patients received concomitant extensive mediastinal lymphadenectomy, resection of adjacent structures (aorta, vena cava, thoracic wall), and neoadjuvant or planned adjuvant chemotherapy or radiotherapy, or both. Operative and perioperative complications were recorded, and patients were followed up for a mean of 15 +/- 21.2 months (range, 9 to 126). RESULTS: Perioperative mortality was 4.3% (n = 4; pulmonary embolism, sepsis, cardiac arrest, and sudden death in 1 patient each). Perioperative complications occurred in 2 patients: renal failure and hemiplegia in 1 patient and cardiac tamponade in 1 patient. The latter complication, caused by tight reconstruction of the pericardium, was directly related to the applied method and required reoperation. No evidence of postpneumonectomy bronchopleural fistula was observed perioperatively and during the whole follow-up. One-year and 2-year survival was 65.7% and 44.8%, respectively. CONCLUSIONS: Bronchial stump reinforcement with a pericardial flap is a highly effective method for preventing postpneumonectomy bronchopleural fistula in selected patients.

Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.

Bilateral lung transplantation with intra- and postoperatively prolonged ECMO support in patients with pulmonary hypertension.

OBJECTIVE: Lung transplantation for pulmonary hypertension (PH) is usually performed on cardiopulmonary bypass, with the disadvantage of full systemic anticoagulation, uncontrolled allograft reperfusion and aggressive ventilation. These factors can be avoided with intra- and postoperatively prolonged extracorporeal membrane oxygenator (ECMO) support. PATIENTS AND METHODS: Between February 1999 and March 2001, 17 consecutive patients with PH (systolic pulmonary artery pressure >70 mmHg) of different etiologies underwent bilateral lung transplantation (BLTX). There were 11 females and six males in the age range from 7 to 50 years (mean age, 28.4+/-12.9 years). Six patients were preoperatively hospitalized, four in the intensive care unit (ICU), one was on ECMO for 3 weeks pretransplantation, and one was resuscitated and bridged with ECMO for 1 week until transplantation. Femoral venoarterial ECMO support with heparin-coated circuits was set up after induction of anesthesia and discontinued at the end of surgery (n=3) or extended for 12 h median into the postoperative period (n=14). Postoperative ventilation pressure was kept below 25 mmHg. Allograft function at 2 h after discontinuation of ECMO, outcome and adverse events were monitored in all patients. Mean follow up time was 18+/-11.4 months. RESULTS: The perioperative mortality was 5.9% (n=1). Arterial oxygen pressure measured 2 h after weaning from ECMO, and under standard mechanical ventilation with a peak pressure of 25 mmHg and inspired oxygen fraction of 0.4, was 157+/-28 mmHg. The mean pulmonary artery pressures were reduced to 29+/-3,4 from 66+/-15 mmHg before transplantation. Postoperative complications included rethoracotomy due to bleeding (n=4) and temporary left ventricular failure (n=4). Median ICU stay was 12 days. Incidence of rejection within the first 100 days was 0.4 per patient. CONCLUSION: BLTX with intraoperative and postoperatively prolonged ECMO support provides excellent initial organ function due to optimal controlled reperfusion and non-aggressive ventilation. This results in improved outcome even in advanced forms of PH.