José Ramon Matilla

Extracorporeal Membrane Oxygenation Support for Resection of Locally Advanced Thoracic Tumors

BACKGROUND The international experience with resection of advanced thoracic malignancies performed with extracorporeal membrane oxygenation (ECMO) support is limited. We examined our results to assess the risks and benefits of this approach. METHODS We retrospectively analyzed all patients with thoracic malignancies who underwent tumor resection with ECMO support in our department between 2001 and 2010. RESULTS Nine patients (aged 21 to 71 years; mean, 54.8±7.5 years) underwent complex tracheobronchial resections (n=6) or resections of greater thoracic vessels (n=3) under venoarterial (VA) ECMO support. In 7 patients the underlying pathologic condition was non-small cell lung cancer, in 1 patient it was carcinoid tumor, and in 1 patient it was synovial sarcoma. The indication for extracorporeal support was complex tracheobronchial reconstruction (n=5), resection of the descending aorta (n=2), and resection of the inferior vena cava (n=1). ECMO cannulation was central (n=4), peripheral (n=4), or combined (n=1). Mean time on bypass was 110±19 minutes (range 40 to 135 minutes). A complete resection (R0) was achieved in 8 patients (89%). One patient died perioperatively as a result of hepatic necrosis. Eight patients were discharged from the hospital after 7 to 42 days (median, 10 days). Median time in the intensive care unit was 1 day (range, 0 to 36 days). The only complication related to the use of ECMO was a lymphatic fistula in the groin. Mean follow-up time was 38±42 months (range, 9 to 111 months). The actuarial 3-month survival was 88.9%, and the 1-year, 3-year, and 5-year survival was 76.7%. CONCLUSIONS Based on this experience, we consider VA ECMO support to be a safe alternative to cardiopulmonary bypass (CPB) for advanced general thoracic operations.

Extracorporeal membrane oxygenation support for complex tracheo-bronchial procedures

OBJECTIVES The published experience with advanced broncho-plastic procedures performed with extracorporeal membrane oxygenation (ECMO) support is very limited. We examined our results to assess the risks and benefits of this approach. METHODS We retrospectively analysed all patients with thoracic malignancies who underwent complex tracheo-bronchial reconstruction under ECMO support in our department between 2001 and 2013. RESULTS Ten patients (age range 21-81 years, mean 54 ± 11 years) underwent complex tracheo-bronchial reconstructions under veno-arterial ECMO support. In 7 patients, the underlying pathology was non-small-cell lung cancer, in 2 cases carcinoid tumour and in 1 case adenoid cystic carcinoma. ECMO cannulation was central (n = 7) or peripheral (n = 3). Mean time on bypass was 113 ± 17 min (range 70-135 min). A complete resection (R0) was achieved in 8 patients (80%). There was no perioperative mortality. Patients were discharged from the hospital after 7-52 days (median 11 days). Median time on ICU was 1 day (range 1-36 days). There was no complication related to the use of ECMO in this series. Mean follow-up time was 1694 ± 1385 days (range 12-4338). The 1-, 3- and 5-year Kaplan-Meier survival was 100, 74 and 56%, respectively. CONCLUSIONS Based on this experience, we consider veno-arterial ECMO support as a safe and valuable approach for complex airway surgery.

Standard donor lung procurement with normothermic ex vivo lung perfusion: A prospective randomized clinical trial

BACKGROUND Ex vivo lung perfusion (EVLP) was primarily developed for evaluation of impaired donor lungs. The good clinical results raise the question for its possible impact on lungs meeting standard criteria. Before application of EVLP on such lungs enters routine clinical practice, it must be demonstrated whether EVLP would affect or improve outcome when used in standard donor lungs. We performed a prospective randomized trial to investigate the role of EVLP in standard lung transplantation (Tx). METHODS This prospective randomized clinical trial compared patients who underwent Tx with ex vivo evaluated donor lungs with an equivalent patient population without previous EVLP. RESULTS From October 2013 to May 2015, 193 lung Tx were performed at the Medical University of Vienna. During this period, 80 recipient/donor pairs that met the inclusion criteria were included in this trial, 41 pairs in the control group, and 39 in the EVLP group. In the EVLP group, 4 lungs (10.2%) ultimately did not qualify for Tx and were rejected for lung Tx owing to technical reasons (n = 2) and quality criteria (n = 2). Donor and recipient characteristics were comparable in both groups. Total cold ischemic time in the EVLP group was significantly longer for both implanted lungs (first side, 372 minutes vs 291 minutes, p < 0.001; second side, 437 minutes vs 370 minutes, p = 0.001); median duration of surgery showed no differences (277 minutes vs 275 minutes). Median oxygen partial pressure/fraction of inspired oxygen ratio at 24 hours after Tx was 516 (range, 280-557) in the EVLP group and 491 (range, 352-575) in the control group (p = 0.63). Incidence of primary graft dysfunction >1 was lower in the EVLP group at all time points compared with the control group (24 hours, 5.7% vs 19.5%, p = 0.10), and need for post-operative prolonged extracorporeal membrane oxygenation was lower in the EVLP group (5.7% vs 12.2%, p = 0.44). Short-term clinical outcomes did not differ between recipients in the 2 groups. Patients remained intubated (1.6 days vs 1.6 days, p = 0.67), in the intensive care unit (6 days vs 6 days, p = 0.76), and in the hospital (23 days vs 19 days, p = 0.42) for a comparable period of time. The 30-day survival was 97.1% vs 100% (p = 0.46). CONCLUSIONS This study provides evidence that EVLP can safely be used in standard donor lungs. Functional results and perioperative outcome are comparable to those achieved with standard donor lung preservation techniques. As an evaluation tool, EVLP allows clinicians to identify and to possibly exclude lungs with functional impairment. Finally, EVLP can safely extend total preservation time.

Lobar lung transplantation--is it comparable with standard lung transplantation?

Lobar lung transplantation is used mainly for urgent small recipients who are less likely to obtain size matched lungs in due time. Only limited numbers have been published, and we herewith report the largest series of lobar‐LuTX. We analyzed our LuTX database from 1/2001 to 12/2012 and compared the outcome of lobar‐LuTX recipients with those receiving standard LuTX. Seven hundred and seventy‐eighty LuTX (group 1) were performed either in standard technique by implanting the whole lungs (n = 539) or with downsizing by wedge resection of the right middle lobe and/or the left lingula (n = 239). One hundred and thirty‐eight LuTX were performed in lobar technique (group 2) to overcome more pronounced size discrepancies. Patients in group 1 had a different spectrum of diagnoses and were less frequently bridged to LuTX (P < 0.001). Intubation time, ICU stay, and hospital stay were shorter in group 1 (P < 0.001). One‐year survival was 84.8% vs. 65.1%, and 5‐years survival 69.9% vs. 54.9% (P < 0.001). In multivariate analyzes, procedure, diagnosis, and pre‐operative bridging were shown to be significant prognostic factors in survival. Early postoperative outcome in Lobar LuTX was significantly inferior to standard LuTX recipients. However, survival rates of successfully dismissed patients were comparable with standard LuTX (P = 0.168); thereby, Lobar‐LuTX remains an important option in the management of urgent small recipients.

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.

Treatment of primary graft dysfunction after lung transplantation with orally inhaled AP301: A prospective, randomized pilot study

BACKGROUND Primary graft dysfunction (PGD) after lung transplantation (LTx) carries significant morbidity and mortality in the early post-operative period and is associated with the development of chronic lung allograft dysfunction. AP301, an activator of epithelial sodium channel-mediated Na+ uptake represents a new concept for prevention and treatment of pulmonary edema and has shown promising results in the pre-clinical setting. This pilot study investigated the clinical effect of inhaled AP301 on patients with development of PGD > 1 according to International Society of Heart and Lung Transplantation criteria after primary LTx in a high-volume center and was conducted as a randomized, placebo-controlled, single-center pilot-study including 20 patients. All consecutive patients fulfilling inclusion criteria were screened for PGD at arrival on the intensive care unit (ICU) after LTx. After randomization, inhaled AP301 or placebo was administered by nebulizer twice daily for 7 days or until extubation. Otherwise, patients were treated according to routine clinical protocol. Partial pressure of arterial oxygen (Pao2)/fraction of inspired oxygen (Fio2) values were obtained until extubation and assessed as a primary outcome parameter. Patients were monitored for 30 days within the study protocol. RESULTS From July 2013 to August 2014, 20 patients were randomized 1:1 to AP301 (Group 1) or placebo (Group 2). Both groups were comparable with regard to sex (40% women/60% men vs 50% women/50% men), mean age (55 ± 13 vs 54 ± 6 years), comorbidities, and diagnosis leading to LTx. The Pao2/Fio2 ratio at the time of inclusion was comparable in both groups, with a mean 235.65 ± 90.78 vs 214.2 ± 95.84 (p = 0.405), and there was no significant difference in the extravascular lung water index (13.88 ± 5.28 vs 16 ± 6.29 ml/kg, p = 0.476). The primary end point was mean Pao2/Fio2 ratio values between baseline and Day 3. In the AP301 group, only 1 patient was ventilated at Day 4 and no patients were ventilated after Day 4. In the placebo group, 5 patients were ventilated on Day 4 and 2 patients on Days 5, 6, and 7. The mean increase in the Pao2/Fio2 ratio was significantly higher in Group 1 patients, and the mean between baseline and at 72 hours was 365.6 ± 90.4 in Group 1 vs 335.2 ± 42.3 in Group 2 (p = 0.049). The duration of intubation was shorter in Group 1 than in Group 2 patients (2 ± 0.82 vs 3.7 ± 1.95 days; p = 0.02). ICU stay was 7.5 ± 3.13 days in Group 1 vs 10.8 ± 8.65 days in group 2 (p = 0.57). Survival at 30 days was 100%. No severe adverse events were recorded. CONCLUSIONS This study was designed as a proof-of-concept pilot study. Although it was not powered to achieve statistical significances, the study demonstrated relevant clinical effects of inhaled AP301 on patients with PGD after primary LTx. The improved gas exchange led to a significantly shorter duration of mechanical ventilation and a trend towards a shorter ICU stay. Further investigation of AP301 for treatment of PGD in larger studies is warranted. TRIAL REGISTRATION The trial is registered at https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000716-21/AT.

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

Abstract 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.

Chylothorax in a 32-Year-Old Patient with Lymphangioleiomyomatosis after Bilateral Lung Transplant

We report the case of a 32-year-old woman with persistent chylothorax after double-lung transplant for lymphangioleiomyomatosis. Dietary restrictions failed to decrease chylous effusions, making surgical revision necessary. The choice of an abdominal approach and postoperative treatment with somatostatin proved successful. The patient showed no recurrence of chylothorax at her 2-year follow up.

Initial experience with a combined sequential left-sided and subxiphoid video-assisted thoracic surgery approach for resection of large anterior mediastinal tumors

Background: There is no standard surgical approach to deal with anterior mediastinal disorders specially tumors with a diameter larger than 4 cm. Radical resection and speciment retrieval in minimally invasive surgery can be challenging. Methods: We describe the first 4 cases of our initial experience dealing with large anterior mediastinal masses in a minimally invasive way. We combined the left side video-assisted thoracic surgery (VATS) approach with a single subxiphoid incision to achieve radical resection and remove the specimen at the end of the procedure without rib spreading. Results: The operative time ranged from 117 to 151 minutes. Blood loss was less than 150 mL during the procedures. Patients were discharged at the third post-operative day with minimal discomfort at the subxiphoid region. No morbidity/mortality was observed. Conclusions: Such procedure offers a safe option to deal with lesions without apparent invasion of other organs (mainly thymic tumors), allowing a good exposure for safe radical resection and for preserving both phrenic nerves. In the future we will consider this combined approach for lesions with a diameter of more than 4 cm and no radiological signs of infiltration.

AB019. PS01.01. Diagnostic and prognostic implications of fibrinogen, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in thymic epithelial tumors

A total of 122 patients with thymic epithelial tumors (TET) were recruited for this cohort study in order to study the utility of serum fibrinogen concentrations and the use of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as prognostic indicators. There were 75.4% thymomas and 24.6% thymic carcinomas. Seventy percent presented in Masaoka-Koga stages I and II. Fibrinogen serum concentrations were significantly higher in patients with TETs (390.2±11.4 mg/dL) compared to healthy volunteers (314.8±10.7 mg/dL; P<0.001). We also detected significantly elevated NLR and PLR in patients with TETs (NLR 3.4±0.3 and PLR 179.8±12.1) compared to controls (NLR 1.8±0.1 and PLR 133.4±7.1; P<0.001 and P=0.010); respectively. After differentiating tumors into those with early tumor stage (stage I-II) and those with advanced tumor stage (stage IIIIV), we found significantly higher Fibrinogen levels, NLR and PLR in patients with advanced tumor stages compared to those with early tumor stages (P=0.002, P=0.040 and P=0.008; respectively). High Fibrinogen serum concentration was associated with significantly worse cause-specific survival (CSS) and freedom-from recurrence (FFR) in patients with TETs (P=0.001 and P=0.043). Patients with high NLR showed significantly worse FFR (P=0.008), while those with high PLR showed significantly worse CSS (P=0.032). Patients who developed tumor recurrence had significantly higher NLR (P=0.024) and PLR (P=0.042) at follow-up compared to patients without recurrence.