Tumour immune microenvironment in resected thymic carcinomas as a predictor of clinical outcome.

BACKGROUND: The spatial distribution of tumour-infiltrating lymphocytes (TILs) is a novel descriptor characterising the tumour immune microenvironment (TIME). The aim of our study was to assess whether a specific TIME of surgically resected thymic carcinoma (TC) can predict tumour invasiveness, recurrence or survival. METHODS: Digital microscopy was performed on 39 TCs immunohistochemically stained to investigate the activation of the immune checkpoint pathway (PD-L1/PD-1), along with density and spatial distribution of TILs phenotypes (CD3+, CD4+, CD8+, FOXP3+, CD56+). The impact of PD-L1 and TIL density considering the intratumoural (iTILs) and stromal (sTILs) distribution on pathological characteristics and clinical outcomes were analysed. RESULTS: In early TC stages, we observed a higher total density of CD3+ (p = 0.05) and CD8+ (p = 0.02) TILs. PD-L1 was expressed in 71.8% of TCs. In advanced TC stages, we observed a lower density of CD3+ (p = 0.04) and CD8+ (p = 0.01) iTILs compared to early stages. Serum concentrations of PD-L1 were significantly higher in TCs compared to healthy controls: 134.43 ± 18.51 vs. 82.01 ± 6.34 pg/ml (p = 0.001), respectively. High densities of stromal CD4+ TILs (54 vs. 32%, p = 0.043) and CD8+ TILs (65 vs. 17%, p = 0.048) were associated with improved freedom from recurrence (FFR) and cause-specific survival (CSS). High density of FoxP3+ TILs were associated with improved FFR (p = 0.03) and CSS (p = 0.003). DISCUSSION: Mapping TIL subpopulations complement the armamentarium for prognostication of TC outcomes. The improved outcome in patients with high density of TILs supports the use of immune checkpoint inhibitors in TC patients.

Short-term and sustained clinical response following thymectomy in patients with myasthenia gravis.

BACKGROUND AND PURPOSE: This study was undertaken to investigate short- and long-term outcome following thymectomy in patients with acetylcholine receptor antibody (AChR-Ab)-positive myasthenia gravis (MG). METHODS: Rates of clinical response (defined as minimal manifestation, pharmacological remission, or complete stable remission) lasting for at least 1 year were retrospectively analyzed using Cox proportional hazard models. The occurrence of relapses was recorded during follow-up. Clinical factors associated with achieving an initial or a sustained response were analyzed. RESULTS: Ninety-four patients with a median age of 33 years (interquartile range [IQR] = 22-51), 68% with nonthymomatous MG and 32% with thymoma-associated MG, were included. An initial clinical response was reached in 72% (68/94). Neither sex, age at onset, thymus histology, delay to surgery after disease onset, surgical approach, corticosteroid treatment, nor clinical severity before thymectomy was significantly associated with achieving this endpoint. During long-term follow-up (median = 89.5 months, IQR = 46-189.5), only half of the patients with an initial response (34/68) had a sustained response without relapses. No clinical factors predicted whether the response would become sustained. In patients without immunosuppressive treatment before thymectomy (n = 24), a high AChR-Ab reduction rate after thymectomy was associated with a higher likelihood of achieving an initial response (p = 0.03). CONCLUSIONS: Sustained long-term clinical response of MG patients after thymectomy is significantly lower than the initial response rates would suggest. The observation that none of the evaluated clinical factors was associated with a worse outcome supports the current clinical practice of patient selection for thymectomy. The relative decline of AChR-Abs after surgery appears to be a promising prognostic marker.

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.

Donor ventilation parameters as predictors for length of mechanical ventilation after lung transplantation: Results of a prospective multicenter study.

BACKGROUND: The evaluation of donor lungs heavily depends on the subjective judgment of the retrieval surgeon. As a consequence, acceptance rates vary significantly among transplant centers. We aimed to determine donor ventilation parameters in a prospective study and test if they could be used as objective quality criteria during organ retrieval. METHODS: A prospective evaluation of lung donors was performed in 3 transplant centers. Ventilation parameters were collected at the time of retrieval using a standardized ventilation protocol. Recipient length of mechanical ventilation (LMV) was defined as the primary end point, and collected data was used to build linear models predicting LMV. RESULTS: In total, 166 donors were included in this study. Median LMV after transplantation was 32 hours (interquartile range: 20-63 hours). Peak inspiratory pressure and dynamic compliance (Cdyn) at the time of retrieval, but not the partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio, correlated with recipient LMV in Spearman correlations (r = 0.280, p = 0.002; r = -0.245, p = 0.003; and r = 0.064, p = 0.432, respectively). Linear models were built to further evaluate the impact of donor ventilation parameters on LMV. The first model was based on donor P/F ratio, donor age, donor intubation time, donor smoking history, donor partial pressure of carbon dioxide, aspiration, chest trauma, and pathologic chest X-ray. This model performed poorly (multiple R-squared = 0.063). In a second model, donor ventilation parameters were included, and Cdyn was identified as the strongest predictor for LMV. The third model was extended by recipient factors, which significantly improved the robustness of the model (multiple R-squared = 0.293). CONCLUSION: In this prospective evaluation of donor lung parameters, currently used donor quality criteria poorly predicted recipient LMV. Our data suggest that Cdyn is a strong donor-bound parameter to predict short-term graft performance; however, recipient factors are similarly relevant.

Ventilation parameters and early graft function in double lung transplantation.

BACKGROUND: Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post-lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU). METHODS: A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (PIP), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest. RESULTS: In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16-47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27-50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5-78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27-86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (PIP, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679. CONCLUSIONS: The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.

Thymic minimally invasive surgery: state of the art across the world-Europe.

In this brief review of selected peer-reviewed literature on thymic minimally-invasive surgery (MIS) we sought to identify if there is a unique approach to thymic MIS on the European continent.

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.

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.