Normothermic machine perfusion is clinically used to assess the quality of marginal donor lungs. Although subnormothermic temperatures have proven beneficial for other solid organ transplants, subnormothermia-related benefits of ex vivo lung perfusion (EVLP) still need to be investigated. Material and Methods: In a rat model, we evaluated the effects of 28 °C temperature on 4-h EVLPs with subsequent left lung transplantation. The recipients were observed for 2 h postoperatively. Lung physiology data were recorded and metabolic parameters were assessed. Results: During the 4-h subnormothermic EVLP, the lung oxygenation was significantly higher (p < 0.001), pulmonary vascular resistance (PVR) lower and dynamic compliance (Cdyn) higher when compared to the 37 °C EVLP. During an end-of-EVLP stress test, we recorded significantly higher flow (p < 0.05), lower PVR (p < 0.05) and higher Cdyn (p < 0.01) in the 28 °C group when compared to the 37 °C group. After the left lung transplantation, Cdyn and oxygenation improved in the 28 °C group, which were comparable to the 37 °C group. Chemokines RANTES, MIP-3α, MIP-1α MCP-1 GRO/KC and pro-inflammatory mediators GM-CSF, G-CSF and TNFα were significantly lower after the 28 °C EVLP and remained low in the plasma of the recipient rats after transplantation. The lungs of the 28 °C group showed significantly lowered myeloperoxidase activity and lowered levels of TNFα and IL-1β. Conclusions: Compared to the normothermic perfusion, the 28 °C EVLP improved Cdyn and PVR and reduced both the release of pro-inflammatory cytokines and myeloperoxidase activity in lung tissue. These observations were also observed after the left lung transplantation in the subnormothermic group. The 28 °C EVLP significantly improved biochemical, physiological and inflammatory parameters in lung donors.

Background: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We hypothesized that perfluorocarbon-based oxygen carrier, a novel reconditioning strategy instilled during EVLP would improve graft function. Methods: We utilized perfluorocarbon-based oxygen carrier (PFCOC) during EVLP to recondition and improve lung graft function in a pig model of EVLP and lung transplantation. Lungs were retrieved and stored for 24 h at 4 °C. EVLP was done for 6 h with or without PFCOC. In the transplantation groups, left lung transplantation was done after EVLP with or without PFCOC. Allograft function was assessed by means of pulmonary gas exchange, lung mechanics and vascular pressures, histology and transmission electron microscopy (TEM). Results: In the EVLP only groups, physiological and biochemical markers during the 6-h perfusion period were comparable. However, perfusate lactate potassium levels were lower and ATP levels were higher in the PFCOC group. Radiologic assessment revealed significantly more lung infiltrates in the controls than in the PFCOC group (p = 0.04). In transplantation groups, perfusate glucose consumption was higher in the control group. Lactate levels were significantly lower in the PFCOC group (p = 0.02). Perfusate flavin mononucleotide (FMN) was significantly higher in the controls (p = 0.008). Post-transplant gas exchange was significantly better during the 4-h reperfusion period in the PFCOC group (p = 0.01). Plasma IL-8 and IL-12 levels were significantly lower in the PFCOC group (p = 0.01, p = 0.03, respectively). ATP lung tissue levels at the end of the transplantation were higher and myeloperoxidase (MPO) levels in lung tissue were lower in the PFCOC group compared to the control group. In the PFCOC group, TEM showed better tissue preservation and cellular viability. Conclusion: PFCOC application is safe during EVLP in lungs preserved 24 h at 4 °C. Although this strategy did not significantly affect the EVLP physiology, metabolic markers of the donor quality such as lactate production, glucose consumption, neutrophil infiltration and preservation of mitochondrial function were better in the PFCOC group. Following transplantation, PFCOC resulted in better graft function and TEM showed better tissue preservation, cellular viability and improved gas transport.

The quality of marginal donor lungs is clinically assessed with normothermic machine perfusion. Although subnormothermic temperature and perfluorocarbon-based oxygen carriers (PFCOC) have proven favourable for other organ transplants, their beneficial use for ex vivo lung perfusion (EVLP) still requires further investigation. In a rat model, we evaluated on a 4 h EVLP time the effects of PFCOC with either 28 °C or 37 °C perfusion temperatures. During EVLP at 28 °C with PFCOC, we recorded significantly lower lung pulmonary vascular resistance (PVR), higher dynamic compliance (Cdyn), significantly lower potassium and lactate levels, higher lung tissue ATP content, and significantly lower myeloperoxidase tissue activity when compared to the 37 °C EVLP with PFCOC. In the subnormothermic EVLP with or without PFCOC, the pro-inflammatory mediator TNFα, the cytokines IL-6 and IL-7, the chemokines MIP-3α, MIP-1α, MCP-1, GRO/KC as well as GM-CSF, G-CSF and the anti-inflammatory cytokines IL-4 and IL-10 were significantly lower. The 28 °C EVLP improved both Cdyn and PVR and decreased pro-inflammatory cytokines and pCO2 levels compared to the 37 °C EVLP. In addition, the 28 °C EVLP with PFCOC produced a significantly lower level of myeloperoxidase activity in lung tissue. Subnormothermic EVLP with PFCOC significantly improves lung donor physiology and ameliorates lung tissue biochemical and inflammatory parameters.

Objectives We aimed to compare the currently used nodal staging system (pN) with the number of metastatic lymph node (LN) stations (sN) and the number of metastatic LNs (nN) on survival in patients with NSCLC. Methods Between 2010 and 2017, 1038 patients resected for NSCLC were analyzed. We performed three-different stratifications of LN status assessment: pN-category (pN0, pN1 and pN2); sN-category (sN0, sN1; one station metastasis, sN2; two-three stations metastases, and sN3; ≥ 4 stations metastasis); nN-category (nN0, nN1; one-three LNs metastasis, nN2; four-six Lns metastasis, and nN3; ≥ 7 LNs metastasis). Results Five-year survival rate was 70.1% for N0 in all classifications. It was 54.3% for pN1, and 26.4% for pN2 (p < 0.0001). Five-year survival rates for N1, N2, and N3 categories were 54.1%, 42.4% and 16.1% according to sN, and 51.4%, 36.1%, and 7.9% according to nN, respectively (p < 0.0001). In multivariate analysis, sN and nN were independent risk factors such as pN (p < 0.0001). Hazard ratios versus N0 for N1, N2, and N3 were more significant for sN and nN than pN (1.597, 2.176, and, 3.883 for sN, 1.645, 2.658, and, 4.118 for nN, and 1.576, 3.222 for pN, respectively). When the subcategories of sN and nN were divided into pN1 and pN2 subgroups, the anatomic location of the LN involvement lost importance as tumor burden and tumor spreading increased. Conclusion The number of metastatic LN stations and the number of metastatic LNs are better prognostic factors than currently used nodal classification in NSCLC. Ziele Die Anzahl der metastasierten LN-Stationen und die Anzahl der metastasierten LNs sind bessere prognostische Faktoren als die derzeit verwendete nodale Klassifikation in NSCLC. Methoden Zwischen 2010 und 2017 wurden 1038 resezierte Patienten für NSCLC analysiert. Wir haben 3 verschiedene Schichten für die LN-Zustandsbewertung durchgeführt: pN-Kategorie (pN0, pN1 und pN2); sN-Kategorie (sN0, sN1; 1. Station der Metastase, sN2; die 2. und 3. Station der Metastasen und sN3; ≥ 4. Station der Metastasen); die nN-Kategorie (nN0, nN1; 3 LNs Metastase, nN2; Metastasen in 4 – 6 LNs und nN3; Metastasen in ≥ 7 LNs). Ergebnisse Die 5-Jahres-Überlebensrate betrug 70,1% für N0 in allen Klassifikationen. Sie lag bei 54,3% für pN1 und 26,4% für pN2 (p < 0,0001). Die 5-Jahres-Überlebensrate für die Kategorien N1, N2 und N3 betrug 54,1%, 42,4% und 16,1% nach sN und 51,4%, 36,1% und 7,9% nach nN (p < 0,0001). In der multivariaten Analyse waren sN und nN unabhängige Risikofaktoren wie pN (p < 0,0001). Die Gefahrenverhältnisse gegenüber N0 für N1, N2 und N3 waren für sN und nN signifikanter als für pN (1,597, 2,176 und 3,883 für sN; 1,645, 2,658 und 4,118 für nN bzw. 1,576, 3,222 für pN). Bei der Einteilung der Unterkategorien von sN und nN in den pN1- und pN2-Subgruppen verloren die anatomische Lage der LN-Beteiligung mit zunehmender Tumorbelastung und Tumorausbreitung an Bedeutung. Fazit Die Anzahl der metastasierten LN-Stationen und die Anzahl der metastasierten LNs sind bessere prognostische Faktoren als die derzeit verwendete nodale Klassifikation in NSCLC. ^* Presentation: Presented at the Oral Presentation Session of the 26th European Conference on General Thoracic Surgery, Ljubljana/Slovenia/2018; winner of the ESTS/the Deutsche Gesellschaft für Thoraxchirurgie Travel Grant Award

OBJECTIVES: The newly proposed N subclassification (new-N) was compared with the combined anatomical location and ratio of the number of metastatic lymph nodes to the total number of resected lymph nodes (anatomic-LNR) in terms of prognosis in resected lung cancer patients. METHODS: Between 2005 and 2018, 961 patients who underwent lung cancer resection were catergorized into the pN1-single (N1a; n = 281), pN1-multiple (N1b; n = 182), pN2-single with skip metastasis (N2a1; n = 116), pN2-single with N1 metastasis (N2a2; n = 222) and pN2-multiple (N2b; n = 160) groups based on new-N. The optimal cut-off points for survival in pN1 and pN2 patients were determined using the best sensitivity and specificity scores, calculated using receiver operating characteristic analysis. RESULTS: The difference in survival between N1a and N1b patients was statistically significant (P = 0.001), but there was no significant difference in the survival rates of N1b and N2a1 (P = 0.52). The survival curves for N2a1 and N2a2 patients almost overlapped (P = 0.143). N2a2 patients showed a better survival rate than N2b patients, with no significant difference (P = 0.132). The cut-off points for LNR were 0.10 and 0.25 for pN1 and pN2 patients, respectively, according to receiver operating characteristic analysis for survival. Based on receiver operating characteristic analysis, pN patients were categorized into the N1-lowLNR (n = 232), N1-highLNR (n = 231), N2-lowLNR (n = 266) and N2-highLNR (n = 232) groups. The 5-year survival rate was 62.9%, 49.8%, 41.1% and 27.1% for N1-lowLNR, N1-highLNR, N2-lowLNR and N2-highLNR, respectively (P < 0.001). CONCLUSIONS: LowLNR is associated with better survival than highLNR in resected lung cancer patients. Anatomic-LNR shows a high discriminatory power for prognosis.

Blood gas analysis,epidural analgesia,opioid analgesics,respiratory function tests,thoracotomy