Preoperative risk factors predict perioperative allogenic blood transfusion in patients undergoing primary lung cancer resections: a retrospective cohort study from a high-volume thoracic surgery center.

BACKGROUND: Our study aimed to identify preoperative predictors for perioperative allogenic blood transfusion (ABT) in patients undergoing major lung cancer resections in order to improve the perioperative management of patients at risk for ABT. METHODS: Patients admitted between 2014 and 2016 in a high-volume thoracic surgery clinic were retrospectively evaluated in a cohort study based on a control group without ABT and the ABT group requiring packed red blood cell units within 15 days postoperatively until discharge. The association of ABT with clinically established parameters (sex, preoperative anemia, liver and coagulation function, blood groups, multilobar resections) was analyzed by contingency tables, receiver operating characteristics (ROC) and logistic regression analysis, taking into account potential covariates. RESULTS: 60 out of 529 patients (11.3%) required ABT. N1 and non-T1 tumors, thoracotomy approach, multilobar resections, thoracic wall resections and Rhesus negativity were more frequent in the ABT group. In multivariable analyses, female sex, preoperative anemia, multilobar resections, as well as serum alanine-aminotransferase levels, thrombocyte counts and Rhesus negativity were identified as independent predictors of ABT, being associated with OR (95% Confidence interval, p-value) of 2.44 (1.23-4.88, p = 0.0112), 18.16 (8.73-37.78, p < 0.0001), 5.79 (2.50-13.38, p < 0.0001), 3.98 (1.73-9.16, p = 0.0012), 2.04 (1.04-4.02, p = 0.0390) and 2.84 (1.23-6.59, p = 0.0150), respectively. CONCLUSIONS: In patients undergoing major lung cancer resections, multiple independent risk factors for perioperative ABT apart from preoperative anemia and multilobar resections were identified. Assessment of these predictors might help to identify high risk patients preoperatively and to improve the strategies that reduce perioperative ABT.

Predicting Long-term Survival After Lung Metastasectomy in Patients With Malignant Germ-cell Tumors.

BACKGROUND/AIM: The aim of the study was to identify predictors of long-term survival and propose an improved risk stratification in patients with pulmonary germ-cell metastases admitted for pulmonary metastasectomy. PATIENTS AND METHODS: Thirty-four patients admitted to the Division of Thoracic Surgery Munich, Germany, from 04/1994 until 09/2017 were retrospectively analyzed. The impact of clinical parameters on survival was calculated using Kaplan-Meier, multivariate Cox regression analysis and receiver-operator curves. RESULTS: Ten-year overall survival was 75.3%. Elevated American Society of Anesthesiologists score, metachronous metastasis, embryonal histology, intrathoracic lymph node involvement, brain metastases and thoracic wall infiltration were significant predictors of reduced survival. With the independent predictors (embryonal histology, metachronous metastasis and thoracic wall infiltration), a germinal non-seminomatous lung metastasis risk of death score (GLUMER) was calculated, accurately predicting survival (area under curve=0.8839, p=0.0023). CONCLUSION: In patients with pulmonary germ-cell metastases, intrathoracic lymph node involvement, embryonal carcinoma, metachronous metastasis and thoracic wall infiltration represent negative predictors of long-term survival. The GLUMER score might represent a promising tool for use in adapted follow-up care in high-risk patients.

Prevention of COVID-19 in Thoracic Surgery Patients: Lessons Learned during the First Pandemic Wave.

BACKGROUND: The aim of this retrospective study was to investigate the implementation of measures to prevent perioperative COVID-19 in thoracic surgery during the first wave of the COVID-19 pandemic 2020 allowing a continued surgical treatment of patients. METHODS: The implemented preventive measures in patient management of the thoracic surgery department of the Asklepios Lung Clinic Munich-Gauting, Germany were retrospectively analyzed. Postoperative COVID-19 incidence before and after implementation of preventive measures was investigated. Patients admitted for thoracic surgical procedures between March and May 2020 were included in the study. Patient characteristics were analyzed. For the early detection of putative postoperative COVID-19 symptoms, typical post-discharge symptomatology of thoracic surgery patients was compared to non-surgical patients hospitalized for COVID-19. RESULTS: Thirty-five surgical procedures and fifty-seven surgical procedures were performed before and after implementation of the preventive measures, respectively. Three patients undergoing thoracic surgery before implementation of preventive measures developed a COVID-19 pneumonia post-discharge. After implementation of preventive measures, no postoperative COVID-19 cases were identified. Fever, dyspnea, dry cough and diarrhea were significantly more prevalent in COVID-19 patients compared to normally recovering thoracic surgery patients, while anosmia, phlegm, low energy levels, body ache and nausea were similarly frequent in both groups. CONCLUSIONS: Based on the lessons learned during the first pandemic wave, we here provide a blueprint for successful easily implementable preventive measures minimizing SARS-CoV-2 transmission to thoracic surgery patients perioperatively. While symptoms of COVID-19 and the normal postoperative course of thoracic surgery patients substantially overlap, we found dyspnea, fever, cough, and diarrhea significantly more prevalent in COVID-19 patients than in normally recovering thoracic surgery patients. These symptoms should trigger further diagnostic testing for postoperative COVID-19 in thoracic surgery patients.

Clinical Course of Three Postoperative Symptomatic COVID-19 Cases in Patients After Lung Lobectomy.

The novel coronavirus disease 2019 is a highly contagious viral infection caused by the severe acute respiratory syndrome coronavirus 2 virus. Its rapid spread and severe clinical presentation influence patient management in all specialties including thoracic surgery. We report 3 cases of coronavirus disease 2019 occurring in patients shortly after thoracotomy and thoracoscopy procedures, illustrating the imminent threat of severe acute respiratory syndrome coronavirus 2 infection for thoracic surgery patients.

[Expert Recommendation for the Implementation of Hyperthermic Intrathoracic Chemotherapy (HITOC) in Germany]. / Expertenempfehlung zur Anwendung der hyperthermen intrathorakalen Chemotherapie (HITOC) in Deutschland.

INTRODUCTION: During the last few years, hyperthermic intrathoracic chemotherapy (HITOC) has been performed in several departments for thoracic surgery in Germany. The objective of this expert recommendation is to provide elementary recommendations for a standardised HITOC treatment, which are based on clinical experiences and research data. METHODS: Between October and December 2018, a group of experts for thoracic surgery in five departments of thoracic surgery developed recommendations for the HITOC procedure in Germany. These experts were selected by the latest national survey for HITOC and had the most clinical experience with HITOC. All recommendations are based on clinical experience, the experts' research data and recent literature. RESULTS: All recommendations were evaluated by all participating departments in one consensus survey. Finally, a total of six main conclusions including a total of 17 recommendations were developed. For each recommendation, the strength of the consensus is presented in percentages. 100% agreement was established for nomenclature, technique, the chemotherapeutic agent, the perioperative management, the safety measures and the indications for HITOC. All experts recommended cisplatin as the first choice chemotherapeutic agent for HITOC. The dosage of cisplatin is specified in mg/m2 body surface area (BSA) and should be between 150 and 175 mg/m2 BSA. The volume of the perfusion fluid (approximately 4 - 5 l) seems to play a role for the concentration gradient of cisplatin and should therefore also be taken into account. CONCLUSIONS: These expert recommendations provide a standardised and consistent implementation of the HITOC procedure. On this basis, postoperative complications associated to HITOC should be reduced and comparison of the results should be improved.

Pleurectomy/decortication and hyperthermic intrathoracic chemoperfusion using cisplatin and doxorubicin for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITHOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITHOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. METHODS: From 2009 until 2013, 71 patients with localized pleural mesothelioma underwent pleurectomy and decortication followed by HITHOC with cisplatin and doxorubicin. We analyzed postoperative morbidity, age, overall survival and influence of macroscopic resection on survival. RESULTS: Median patient age was 70 years (range, 65-73 years). Patients having the sarcomatoid subtype of mesothelioma showed a poor median survival of 9.2 months. In contrast, patients having the epithelioid subtype had a median survival of 17.9 months. Patients following macroscopic complete resection had a significantly better survival with 28.2 months compared to 13.1 months in patients with incomplete resection of the mesothelioma (P<0.0001). HITHOC was performed in all patients after tumor resection using cisplatin and doxorubicin. CONCLUSIONS: Taken together, HITHOC following pleurectomy and decortication is supposed to be a safe therapeutic option for selected patients with localized epithelial pleural mesothelioma.

Tacrolimus preconditioning of rat liver allografts impacts glutathione homeostasis and early reperfusion injury.

OBJECTIVE: To characterize the immunosuppressant tacrolimus as a protective antioxidant in rat liver transplantation. METHODS: Livers of male Lewis rats underwent 24 h of hypothermic preservation in UW solution and were rinsed with tacrolimus or placebo directly before transplantation. Markers of liver injury, such as enzymes and bile flow, were determined during a 2 h reperfusion period. Concentrations of reduced (GSH) and oxidized (GSSG) glutathione were analyzed in plasma, bile, and liver tissue for estimation of oxidant stress caused by reactive oxygen species (ROS). RESULTS: Administration of tacrolimus (10 ng/mL) resulted in decreased ALT plasma levels (1740 ± 1169 U/l versus 3691 ± 1144 U/l; P < 0.05) at 2 h of reperfusion. While endogenous intracellular GSH concentrations remained unchanged, GSSG, the oxidation product of GSH, was markedly decreased at 2 h of reperfusion in preconditioned livers (47.0 ± 10.4 nm/g versus 71.8 ± 30.6 nm/g; P < 0.05). Correspondingly, GSSG bile concentrations (0.19 ± 0.04 mM versus 0.13 ± 0.04 mM; P < 0.05) as well as plasma GSSG levels (2.4 ± 0.3 mM versus 1.4 ± 0.2 mM; P < 0.05) were significantly increased upon reperfusion. These findings suggest that tacrolimus impacts post-ischemic GSH metabolism when administered as a rinse solution for liver allografts through an unknown pathway. CONCLUSION: Hepatocellular injury following transplantation was significantly decreased by preconditioning with tacrolimus. One possible mechanism of action is the detoxification of ROS through the preservation of cytosolic and extracellular GSH/GSSG ratios.

PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation.

AIM: To investigate the in vivo effect of atrial natriuretic peptide (ANP) and its signaling pathway during orthotopic rat liver transplantation. METHODS: Rats were infused with NaCl, ANP (5 microg/kg), wortmannin (WM, 16 microg/kg), or a combination of both for 20 min. Livers were stored in UW solution (4 degrees C) for 24 h, transplanted and reperfused. Apoptosis was examined by caspase-3 activity and TUNEL staining. Phosphorylation of Akt and Bad was visualized by Western blotting and phospho-Akt-localization by confocal microscopy. RESULTS: ANP-pretreatment decreased caspase-3 activity and TUNEL-positive cells after cold ischemia, indicating antiapoptotic effects of ANP in vivo. The antiapoptotic signaling of ANP was most likely caused by phosphorylation of Akt and Bad, since pretreatment with PI 3-kinase inhibitor WM abrogated the ANP-induced reduction of caspase-3 activity. Interestingly, analysis of liver tissue by confocal microscopy showed translocation of phosphorylated Akt to the plasma membrane of hepatocytes evoked by ANP. CONCLUSION: ANP activates the PI-3-kinase pathway in the liver in vivo leading to phosphorylation of Bad, an event triggering antiapoptotic signaling cascade in ischemic liver.

Hepatocyte cytoskeleton during ischemia and reperfusion--influence of ANP-mediated p38 MAPK activation.

AIM: To determine functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischemia and reperfusion. METHODS: For in vivo experiments, animals received ANP (5 microg/kg) intravenously. In a different experimental setting, isolated rat livers were perfused with KH-buffer+/-ANP (200 nmol/L) +/-SB203580 (2 micromol/L). Livers were then kept under ischemic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hsp27 were determined by Western blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin distribution was determined by confocal microscopy. RESULTS: We first confirmed that ANP preconditioning leads to an activation of p38 MAPK and observed alterations of the cytoskeleton in hepatocytes of ANP-preconditioned organs. ANP induced an increase of hepatic F-actin after ischemia, which could be prevented by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580. CONCLUSION: This study reveals that ANP-mediated p38 MAPK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first time shows functional consequences of ANP-induced hepatic p38 MAPK activation.

The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3beta in hepatocellular carcinoma.

BACKGROUND/AIMS: The organic anion transporting polypeptides (OATPs) mediate the uptake of numerous amphipathic compounds into hepatocytes. Our aim was to study the expression and regulation of OATP8 (OATP1B3, SLC21A8/SLCO1B3) and OATP-C (OATP1B1, SLC21A6/SLCO1B1) in hepatocellular carcinomas (HCC). METHODS: RNA and protein levels in 13 paired HCC and adjacent non-tumor liver samples were quantified by real-time polymerase chain reaction or Western blot, respectively. The OATP8 and OATP-C gene promoters were characterized by luciferase reporter assays and electrophoretic mobility shift assays (EMSA). RESULTS: The expression of OATP8 was decreased in 60% of HCC compared to surrounding non-tumor liver tissue, on both the mRNA and protein levels. Expression of the liver-enriched transcription factor hepatocyte nuclear factor 3beta (HNF3beta) was increased in 70% of HCC and correlated inversely with OATP8 mRNA (r=-0.75, P<0.05) and protein. In contrast to OATP8, expression of OATP-C was not significantly decreased in HCC. In transfected Huh7 cells, OATP8 promoter activity was inhibited by 70% when HNF3beta was cotransfected. An HNF3beta binding site was located at nt -39/-23 by EMSA. The OATP-C promoter was not inhibited by HNF3beta. CONCLUSIONS: HNF3beta represses transcription of the OATP8 but not the OATP-C gene, providing a mechanism for reduced expression of OATP8 in HCC.