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Simple Summary: Long-term immunosuppressive therapy following liver transplantation is associated with an increased risk for the development of de novo lung carcinoma. However, data on the management of the immunosuppression following the diagnosis of lung cancer are missing to the present day. In this retrospective analysis, we investigate factors associated with improved survival of liver transplant recipients with diagnosis of de novo lung carcinoma with a particular emphasis on the impact of immunosuppression. Our findings suggest that strict reduction of immunosuppression has a beneficial effect on survival in this particular situation and, thus, should be an early intervention following diagnosis. Liver transplant recipients with the diagnosis of de novo lung cancer should be offered surgical treatment if technically feasible as a potential curative therapeutic option to improve limited prognosis. Further investigations concerning dosage findings and reduction of immunosuppression in organ recipients should be the targets of subsequent studies. Abstract: (1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution's register of liver allograft recipients (Charite-Universitatsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7-27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0-196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.

Safak Gül-Klein,1 Henriette Hegermann,1 Robert Röhle,2– 4 Moritz Schmelzle,1 Frank Tacke,5 Wenzel Schöning,1 Robert Öllinger,1 Tomasz Dziodzio,1 Patrick Maier,1 Julius M Plewe,1 David Horst,6 Igor Maximilian Sauer,2 Johann Pratschke,1 Nils Lachmann,7 Dennis Eurich1 1Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany; 2Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany; 3Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Coordinating Center for Clinical Studies, Berlin, Germany; 4Berlin Institute of Health (BIH), Berlin, Germany; 5Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Hepatology & Gastroenterology, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany; 6Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology, Charité – Universitätsmedizin Berlin, Berlin, Germany; 7Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, HLA Laboratory, Institute of Transfusion Medicine, Histocompatibility and Immunogenetics, Charité - Universitätsmedizin, Berlin, GermanyCorrespondence: Safak Gül-KleinDepartment of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, GermanyTel +49 30 450 652 195Fax +49 30 450 552 900Email safak.guel@charite.deBackground: Donor-specific antibodies (DSA) against donor human leukocyte antigen after liver transplantation, which are associated with histological changes, have been widely studied with respect to their sustained impact on transplant function. However, their long-term impact after liver transplantation remains unclear.Methods: We performed a cross-sectional analysis from June 2016 to July 2017 that included all patients who presented themselves for scheduled follow-up after receiving a liver transplantation between September 1989 and December 2016. In addition to a liver protocol biopsy, patients were screened for human leukocyte antigen antibodies (HLAab) and donor-specific antibodies. Subsequently, the association between human leukocyte antigen antibodies, donor-specific antibodies, histologic and clinical features, and immunosuppression was analyzed.Results: Analysis for human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was performed for 291 and 271 patients. A significant association between higher inflammation grades and the presence of human leukocyte antigen antibodies and donor-specific antibodies was detected, while fibrosis stages remained unaffected. These results were confirmed by multivariate logistic regression for inflammation showing a significant increase for presence of human leukocyte antigen antibodies and donor-specific antibodies (OR: 4.43; 95% CI: 1.67– 12.6; p=0.0035). Furthermore, the use of everolimus in combination with tacrolimus was significantly associated with the status of negative human leukocyte antigen antibodies and donor-specific antibodies. Viral etiology for liver disease, hepatocellular carcinoma (HCC) and higher steatosis grades of the graft were significantly associated with a lower rate of human leukocyte antigen antibodies. The impact of human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was associated with higher levels of laboratory parameters, such as transaminases and bilirubin.Conclusion: Donor-specific antibodies against donor human leukocyte antigen are associated with histological and biochemical graft inflammation after liver transplantation, while fibrosis seems to be unaffected. Future studies should validate these findings for longer observation periods and specific subgroups.Keywords: human leukocyte antigen antibodies, donor-specific antibodies, liver biopsy, liver transplantation

The COVID-19 pandemic challenges international and national healthcare systems. In the field of thoracic surgery, procedures may be deferred due to mandatory constraints of the access to diagnostics, staff and follow-up facilities. There is a lack of prospective data on the management of benign and malignant thoracic conditions in the pandemic. Therefore, we derived recommendations from 14 thoracic societies to address key questions on the topic of COVID-19 in the field of thoracic surgery. Respective recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found to temporarily suspend non-critical elective procedures or procedures for benign conditions and to prioritize patients with symptomatic or advanced cancer. Prior to hospitalization, patients should be screened for respiratory symptoms indicating possible COVID-19 infection and most societies recommended to screen all patients for COVID-19 prior to admission. There was a weak consensus on the usage of serology tests and CT scans for COVID-19 diagnostics. Nearly all societies suggested to postpone elective procedures in patients with suspected or confirmed COVID-19 and recommended constant reevaluation of these patients. Additionally, we summarized recommendations focusing on precautions in the theater and the management of chest drains. This study provides a novel approach to informed guidance for thoracic surgeons during the COVID-19 pandemic in the absence of scientific evidence-based data.

Additional file 1. Pathogens and detailed antibiotic therapy.

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients &lt, 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p &lt, 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%, p = 0.692, hepatic 3.5% vs. 2.7%, p = 0.788, malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.

DSA characteristics of 113 DSA-positive patients who underwent LT from deceased donors between January 1, 2008 and December 31, 2015.

The Model for End-Stage Liver Disease (MELD)-based allocation system was implemented in Germany in 2006 in order to reduce waiting list mortality. The purpose of this study was to evaluate post-transplant results and waiting list mortality since the introduction of MELD-based allocation in our center and in Germany. Adult liver transplantation at the Charit&eacute, &mdash, Universit&auml, tsmedizin Berlin was assessed retrospectively between 2005 and 2012. In addition, open access data from Eurotransplant (ET) and the German Organ Transplantation Foundation (DSO) were evaluated. In our department, 861 liver transplantations were performed from 2005 to 2012. The mean MELD score calculated with the laboratory values last transmitted to ET before organ offer (labMELD) at time of transplantation increased to 20.1 from 15.8 (Pearson&rsquo, s R = 0.121, p &lt, 0.001, confidence interval (CI) = 0.053&ndash, 0.187). Simultaneously, the number of transplantations per year decreased from 139 in 2005 to 68 in 2012. In order to overcome this organ shortage the relative number of utilized liver donors in Germany has increased (85% versus 75% in non-German ET countries). Concomitantly, 5-year patient survival decreased from 79.9% in 2005 to 60.3% in 2012 (p = 0.048). At the same time, the ratio of waiting list mortality vs. active-listed patients nearly doubled in Germany (Spearman&rsquo, s rho = 0.903, p &lt, 0.001, CI = 0.634&ndash, 0.977). In low-donation areas, MELD-based liver allocation may require reconsideration and inclusion of prognostic outcome factors.

BACKGROUND Pleural effusions represent a common complication after liver transplantation (LT) and chest drain (CD) placement is frequently necessary. MATERIAL AND METHODS In this retrospective cohort study, adult LT recipients between 2009 and 2016 were analyzed for pleural effusion formation and its treatment within the first 10 postoperative days. The aim of the study was to compare different settings of CD placement with regard to intervention-related complications. RESULTS Overall, 597 patients met the inclusion criteria, of which 361 patients (60.5%) received at least 1 CD within the study period. Patients with a MELD >25 were more frequently affected (75.7% versus 56.0%, P

Although more than one million liver transplantations have been carried out worldwide, the literature on liver resections in transplanted livers is scarce. We herein report a total number of fourteen patients, who underwent liver resection after liver transplantation (LT) between September 2004 and 2017. Hepatocellular carcinomas and biliary tree pathologies were the predominant indications for liver resection (n = 5 each), other indications were abscesses (n = 2), post-transplant lymphoproliferative disease (n = 1) and one benign tumor. Liver resection was performed at a median of 120 months (interquartile range (IQR): 56.5&ndash, 199.25) after LT with a preoperative Model for End-Stage Liver Disease (MELD) score of 11 (IQR: 6.75&ndash, 21). Severe complications greater than Clavien&ndash, Dindo Grade III occurred in 5 out of 14 patients (36%). We compared liver resection patients, who had a treatment option of retransplantation (ReLT), with actual ReLTs (excluding early graft failure or rejection, n = 44). Bearing in mind that late ReLT was carried out at a median of 117 months after first transplantation and a median of MELD of 32 (IQR: 17.5&ndash, 37), three-year survival following liver resection after LT was similar to late ReLT (50.0% vs. 59.1%, p = 0.733). Compared to ReLT, liver resection after LT is a rare surgical procedure with significantly shorter hospital (mean 25, IQR: 8.75&ndash, 49, p = 0.034) and ICU stays (mean 2, IQR: 1&ndash, 8, p &lt, 0.001), acceptable complications and survival rates.