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Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has expanded and spearheaded development in hepatobiliary surgery. Monosegment-ALPPS tests liver regeneration limits and may present as the last feasible curative treatment option. Methods Electronic databases (MEDLINE, Web of Science, Google Scholar, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on mono-ALPPS using a predefined strategy without date or language restrictions. Individual patient data was extracted and analyzed. Results 237 publications were identified. 19 patients were identified to have undergone mono-ALPPS. Primarily, mono-ALPPS has been utilized as curative treatment for CRLM (17 of 19 cases). Successful mono-ALPPS was possible in FLR above 8% SLV. All patients received either chemotherapy alone or in combination with radiotherapy prior to surgery. 8 of 19 patients experienced PHLF grade A or B. There was no in-hospital mortality described. Recurrent disease has occurred in 7 of 19 patients and 3 have died during follow-up. Conclusion Mono-ALPPS is an experimental procedure that provides a reasonably safe opportunity to curatively treat extensive liver malignancies in patients with FLR as low as 8% SLV. PHLF is the most prevalent complication in mono-ALPPS. Mono-ALPPS should be evaluated in a multicentral study setting.

Background Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. Methods In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. Results Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. Conclusions Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population., Tracing of SARS-CoV-2 population transmission chains is still a major challenge. We present an integrated system of genomic surveillance and show it to be capable of detecting infection chains in a large city during ongoing community transmission.

Portal vein arterialization (PVA) is a possible option when hepatic artery reconstruction is impossible during liver resection. The aim of this study was to review the literature on the clinical application of PVA in hepatopancreatobiliary (HPB) surgery.We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched the PubMed, Embase and Web of Science databases until December 2019. Experimental (animal) studies, review articles and letters were excluded.Twenty studies involving 57 patients were included. Cholangiocarcinoma was the most common indication for surgery (40 patients [74%]). An end-to-side anastomosis between a celiac trunk branch and the portal vein was the main PVA technique (35 patients [59%]). Portal hypertension was the most common longterm complication (12 patients [21%] after a mean of 4.1 mo). The median followup period was 12 (range 1-87) months. The 1-, 3- and 5-year survival rates were 64%, 27% and 20%, respectively.Portal vein arterialization can be considered as a rescue option to improve the outcome in patients with acute liver de-arterialization when arterial reconstruction is not possible. To prevent portal hypertension and liver injuries due to thrombosis or overarterialization, vessel calibre adjustment and timely closure of the anastomosis should be considered. Further prospective experimental and clinical studies are needed to investigate the potential of this procedure in patients whose liver is suddenly de-arterialized during HPB procedures.L’artérialisation de la veine porte (AVP) est une option envisageable lorsqu’il est impossible de reconstruire l’artère hépatique au moment d’une résection du foie. Le but de cette étude était de faire le point sur la littérature concernant l’application clinique de l’AVP en cours de chirurgie hépatopancréatobiliaire (HPB).Nous avons procédé à une revue systématique selon les directives PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons interrogé systématiquement les bases de données PubMed, Embase et Web of Science jusqu’à décembre 2019. Les études expérimentales (chez l’animal), les articles de synthèse et les lettres ont été exclus.Vingt études regroupant 57 patients ont été incluses. Le cholangiocarcinome était la plus fréquente indication de la chirurgie (40 patients [74 %]). L’anastomose terminolatérale d’une branche du tronc cæliaque avec la veine porte a été la principale technique d’AVP (35 patients [59 %]). L’hypertension portale a été la plus fréquente complication (12 patients [21 %] après une moyenne de 4,1 mois). Le suivi médian a été de 12 mois (éventail, 1–87 mois). Les taux de survie moyens à 1, 3 et 5 ans ont été de 64 %, 27 % et 20 %, respectivement.L’artérialisation de la veine porte peut être considérée comme une option de dernier ressort pour améliorer l’état des patients victimes d’une désartérialisation hépatique aiguë lorsque la reconstruction artérielle est impossible. Pour prévenir l’hypertension portale et les lésions au foie dues à la thrombose ou à l’hyperartérialisation, il faut veiller à ajuster le calibre vasculaire et fermer rapidement l’anastomose. D’autres études expérimentales et cliniques prospectives s’imposent afin d’analyser le potentiel de cette intervention chez les patients dont le foie se trouve subitement désartérialisé durant une chirurgie HPB.

BackgroundPatient-related risk factors such as diabetes mellitus and obesity are increasing in western countries. At the same time the indications for liver resection in both benign and malignant diseases have been significantly extended in recent years. Major liver resection is performed more frequently in a patient population of old age, comorbidity and high rates of neoadjuvant chemotherapy. The aim of this study was to evaluate whether diabetes mellitus, obesity and overweight are risk factors for the short-term post-operative outcome after major liver resection.MethodsFour hundred seventeen major liver resections (≥ 3 segments) were selected from a prospective database. Exclusion criteria were prior liver resection in patient’s history and synchronous major intra-abdominal procedures. Overweight was defined as BMI ≥ 25 kg/m2and 2and obesity as BMI ≥ 30 kg/m2. Primary end point was 90-day mortality and logistic regression was used for multivariate analysis. Secondary end points included morbidity, complications according to Clavien–Dindo classification, unplanned readmission, bile leakage, and liver failure. Morbidity was defined as occurrence of a post-operative complication during hospital stay or within 90 days postoperatively.ResultsFifty-nine patients had diabetes mellitus (14.1%), 48 were obese (11.6%) and 147 were overweight (35.5%). There were no statistically significant differences in mortality rates between the groups. In the multivariate analysis, diabetes was an independent predictor of morbidity (OR = 2.44, p = 0.02), Clavien–Dindo grade IV complications (OR = 3.6, p = 0.004), unplanned readmission (OR = 2.44, p = 0.04) and bile leakage (OR = 2.06, p = 0.046). Obese and overweight patients did not have an impaired post-operative outcome compared patients with normal weight.ConclusionsDiabetes has direct influence on the short-term postoperative outcome with an increased risk of morbidity but not mortality. Preoperative identification of high-risk patients will potentially decrease complication rates and allow for individual patient counseling as part of a shared decision-making process. For obese and overweight patients, major liver resection is a safe procedure.

BackgroundPost-hepatectomy liver failure contributes significantly to postoperative mortality after liver resection. The prediction of the individual risk for liver failure is challenging. This review aimed to provide an overview of cytokine and growth factor triggered signaling pathways involved in liver regeneration after resection.MethodsMEDLINE and Cochrane databases were searched without language restrictions for articles from the time of inception of the databases till March 2019. All studies with comparative data on the effect of cytokines and growth factors on liver regeneration in animals and humans were included.ResultsOverall 3.353 articles comprising 40 studies involving 1.498 patients and 101 animal studies were identified and met the inclusion criteria. All included trials on humans were retrospective cohort/observational studies. There was substantial heterogeneity across all included studies with respect to the analyzed cytokines and growth factors and the described endpoints.ConclusionHigh-level evidence on serial measurements of growth factors and cytokines in blood samples used to predict liver regeneration after resection is still lacking. To address the heterogeneity of patients and potential markers, high throughput serial analyses may offer a method to predict an individual’s regenerative potential in the future.

International audience; Semiconductor quantum dots (QDs) embedded into polymer microbeads are known to be very attractive emitters for spectral multiplexing and colour encoding. Their luminescence lifetimes or decay kinetics have been, however, rarely exploited as encoding parameter, although they cover time ranges which are not easily accessible with other luminophores. We demonstrate here the potential of QDs made from II/VI semiconductors with luminescence lifetimes of several 10 ns to expand the lifetime range of organic encoding luminophores in multiplexing applications using time-resolved flow cytometry (LT-FCM). For this purpose, two different types of QD-loaded beads were prepared and characterized by photoluminescence measurements on the ensemble level and by single-particle confocal laser scanning microscopy. Subsequently, these lifetime-encoded microbeads were combined with dye-encoded microparticles in systematic studies to demonstrate the potential of these QDs to increase the number of lifetime codes for lifetime multiplexing and combined multiplexing in the time and colour domain (tempo-spectral multiplexing). These studies were done with a recently developed novel luminescence lifetime flow cytometer (LT-FCM setup) operating in the time-domain, that presents an alternative to reports on phase-sensitive lifetime detection in flow cytometry. Flow cytometry (FCM), where either single cells or particles are optically detected in a flow, is an established and widespread multiparametric fluorescence technique used for many routine and research applications in biology, medical diagnostics, and food analysis 1-5. FCM typically relies on organic luminophores for optical encoding and multiplexing as well as analyte quantification 6-10. State-of-the-art FCM instruments are designed to detect spectral and/or intensity codes and can distinguish a large number of different colour and intensity codes, e.g. in the case of bead-based assays 5,11-13. Commonly applied spectral multiplexing approaches utilizing organic lumi-nophores are, however, limited by the spectral overlap of the emission bands of the different encoding dyes which limits the number of distinguishable codes and can require signal compensation and cross talk correction 6,14,15. The exploitation of the luminophore-characteristic luminescence lifetime (LT) as additional encoding parameter could in principle increase the number of accessible codes in flow cytometry analysis, thereby increasing the degree of multiplexing 6,7,14,16-21. Time-resolved fluorescence measurements in flow cytometry and lifetime encoding have been discussed for decades 8,22-28. The concept of lifetime multiplexing in a flow, however, has not been adopted in routine applications up to now due to the limited measurement time per object resulting in reduced photon count numbers 27,29. Moreover, the vast majority of reports on lifetime detection in flow cytometry relies on frequency-domain techniques (phase fluorometry), which used to be less expensive as fast detectors required for photon counting-based detection in the time domain, and present specific applications 8,9,14,18,28,30-32. This has been highlighted e.g., in a recently published comprehensive review article from J.P. Houston et al. 8 , revealing only a very small number of research articles related to cytometry studies in the time domain, mostly associated

Background Indications for liver surgery are expanding fast and complexity of procedures increases. Preoperative mortality risk assessment by scoring systems is debatable. A previously published externally validated Mortality Risk Score allowed easy applicable and precise prediction of postoperative mortality. Aim of the study was to compare the performance of the Mortality Risk Score with the standard scores MELD and P-POSSUM. Methods Data of 529 patients undergoing liver resection were analysed. Mortality Risk Score, the labMELD Score and the P-POSSUM Scores (PS, OS, P-POSSUM mortality %) were calculated. The ROC curves of the three scoring systems were computed and the areas under the curve (C-index) were calculated using logistic regression models. Comparisons between the ROC curves were performed using the corresponding Wald tests. Results Internal validation confirmed that the risk model was predictive for a 90-day mortality rate with a C-index of 0.8421. The labMELD Score had a C-index of 0.7352 and the P-POSSUM system 0.6795 (PS 0.6953, OS 0.5413). The 90-day mortality rate increased with increasing labMELD values (p Conclusions By accurately predicting the risk of postoperative mortality after liver surgery the Mortality Risk Score should be useful at the selection stage. Prediction can be adjusted by use of the well-established labMELD Score. In contrast, the performance of standard P-POSSUM Scores is limited.

Background: Choice of the fraction of inspiratory oxygen (FiO2) is controversial. The objective of this analysis was to evaluate whether intraoperative FiO2 was associated with recurrence-free survival after elective cancer surgery.Methods and Analysis: In this single-center, retrospective study, we analyzed 1,084 patients undergoing elective resection of pancreatic (n = 652), colorectal (n = 405), or hepatic cancer (n = 27) at Heidelberg University Hospital between 2009 and 2016. Intraoperative mean FiO2 values were calculated. For unstratified analyses, the study cohort was equally divided into a low- and a high-FiO2 group. For cancer-stratified analyses, this division was done within cancer-strata. The primary outcome measure was recurrence-free survival until the last known follow-up. Groups were compared using Kaplan–Meier analysis. A stratified log rank test was used to control for different FiO2 levels and survival times between the cancer strata. Cox-regression analyses were used to control for covariates. Sepsis, reoperations, surgical-site infections, and cardiovascular events during hospital stay and overall survival were secondary outcomes.Results: Median FiO2 was 40.9% (Q1–Q3, 38.3–42.9) in the low vs. 50.4% (Q1–Q3, 47.4–54.7) in the high-FiO2 group. Median follow-up was 3.28 (Q1–Q3, 1.68–4.97) years. Recurrence-free survival was considerable higher in the high-FiO2 group (p < 0.001). This effect was also confirmed when stratified for the different tumor entities (p = 0.007). In colorectal cancer surgery, increased FiO2 was independently associated with increased recurrence-free survival. The hazard for the primary outcome decreased by 3.5% with every 1% increase in FiO2. The effect was not seen in pancreatic cancer surgery and we did not find differences in any of the secondary endpoints.Conclusions: Until definite evidence from large-scale trials is available and in the absence of relevant clinical conditions warranting specific FiO2 values, perioperative care givers should aim for an intraoperative FiO2 of 50% in abdominal cancer surgery as this might benefit oncological outcomes.

Importance Comparability of morbidity and mortality rates after total pancreatectomy (TP) reported by different surgical centers is limited. Procedure-specific differences, such as the extent of resection, including additional vascular or multivisceral resections, are rarely acknowledged when postoperative outcomes are reported. Objectives To evaluate postoperative outcomes after TP and categorize different types of TP based on the extent, complexity, and technical aspects of each procedure. Design, Setting, and Participants This single-center study included a retrospective cohort of 1451 patients who had undergone TP between October 1, 2001, and December 31, 2020. Each patient was assigned to 1 of the following 4 categories that reflect increasing levels of procedure-related difficulty: standard TP (type 1), TP with venous resection (type 2), TP with multivisceral resection (type 3), and TP with arterial resection (type 4). Postoperative outcomes among the groups were compared. Main Outcomes and Measures Categorization of different types of TP based on the procedure-related difficulty and differing postoperative outcomes. Results Of the 1451 patients who had undergone TP and were included in the analysis, 840 were men (57.9%); median age was 64.9 (IQR, 56.7-71.7) years. A total of 676 patients (46.6%) were assigned to type 1, 296 patients (20.4%) to type 2, 314 patients (21.6%) to type 3, and 165 patients (11.4%) to type 4 TP. A gradual increase in surgical morbidity was noted by TP type (type 1: 255 [37.7%], type 2: 137 [46.3%], type 3: 178 [56.7%], and type 4: 98 [59.4%]; P

BackgroundThe biliary tree is a rare location of pediatric rhabdomyosarcoma. Due to the low incidence, there is a lack of evidence concerning therapeutic guidelines for this tumor location. In particular, the impact of surgery is discussed controversially.PurposeObjective is to generate evidence-based treatment guidelines for pediatric biliary rhabdomyosarcoma (BRMS). All available published data on therapeutic regimens and important prognostic factors are investigated with a focus on the role of surgery.MethodsA systematic literature search of MEDLINE, Web of Science, and CENTRAL was performed. Patient data were entered individually. Data was pooled and qualitative and quantitative analyses of demographic data, therapy, postoperative/interventional outcomes, relapse, and survival were conducted. In an individual patient data analysis, cox regression was applied to identify key factors predicting the outcome of patients with BRMS.Results65 studies met the inclusion criteria, providing data on 176 patients with BRMS. Individual patient data analysis showed a 5-year overall survival and progression-free survival of 51% and 50% for the total study population. For patients treated after 2000, 5-year OS and PFS was 65% and 59%, respectively. Absence of surgical tumor resection was an independent risk factor for death (Hazard ratio 8.9, 95%-CI 1.8-43.6, p = 0.007) and significantly associated with recurrent disease and disease-related death.ConclusionThis analysis provides comprehensive information on the largest number of patients hitherto reported in the literature. BRMS is still associated with high morbidity and mortality. Surgical tumor resection is essential for appropriate oncological treatment of BRMS. International cooperation studies are needed to enhance evidence and improve the outcome of this orphan disease.Protocol RegistrationPROSPERO (CRD42021228911) https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228911.

Anastasia Murtha-Lemekhova,1,2 Juri Fuchs,1,2 Erik Schulz,1,2 Anthe Suzan Sterkenburg,1 Philipp Mayer,2,3 Jan Pfeiffenberger,2,4 Katrin Hoffmann1,2 1Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany; 2RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany; 3Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Heidelberg, Germany; 4Department of Gastroenterology and Hepatology, Heidelberg University Hospital, Heidelberg, GermanyCorrespondence: Katrin HoffmannDepartment of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, Heidelberg, 69120, GermanyTel +49 6221 56 6110Fax +49 6221 56 5450Email katrin.hoffmann@med.uni-heidelberg.deBackground: Aberrant subtypes of hepatocellular carcinoma (HCC) account for 20– 30% of all HCCs and habitually present a challenge in diagnosis and treatment. Scirrhous hepatocellular carcinoma (s-HCC) is often misdiagnosed as cholangiocarcinoma, fibrolamellar hepatocellular carcinoma, or metastasis.Methods: Electronic databases (PubMed, Web of Knowledge, Google Scholar, Cochrane Library, and WHO International Clinical Trials Registry Platform) were searched for publications on scirrhous hepatocellular carcinoma without date or language restrictions. Quality assessment was performed using a tool proposed by Murad et al for case reports and series. For observational studies, MINORS quality assessment tool was used. This study was registered at PROSPERO (CRD42020212323).Results: S-HCC arises in patients with chronic hepatitis (hepatitis B in 60% and hepatitis C in 21%). S-HCC primarily affects men with a mean age of 55.8 years. Serum AFP is elevated above 20IU/mL in 66.7% of the patients. On ultrasound, s-HCC presents as hypoechoic or mosaic pattern lesions (47.6% each) and causes a retraction of the liver surface (70%) when near the capsule. Delayed enhancement of the tumor is evident in 87.0%. On MRI, 65.0% of s-HCCs show a target appearance. Histopathologic pattern is mostly irregular (97.6%). Lesions show a bulging appearance (100%), septae (85.6%) and a central scar (63.5%), and usually lack central necrosis (75%). Immunohistochemistry shows HepPar 1 positivity in 64.6%, CK7 in 40.7%, and EMA in 41.9%. The 5-year overall survival rate estimates 45.2% and 45.5% of the patients experience a recurrence after hepatectomy.Conclusion: S-HCC is a rare subtype of HCC primarily arising in hepatitis- or cirrhosis-afflicted livers and incorporates atypical radiological and histopathological HCC features. Despite lower recurrence rates, overall survival of patients with s-HCC is poorer than generally for HCC, underlining the need for individualized treatment. Patients with atypical lesions of the liver should be referred to tertiary hospitals for interdisciplinary assessment and treatment.Keywords: scirrhous HCC, s-HCC, rare liver tumors, RELIVE initiative

The pathophysiology of post-hepatectomy liver failure is not entirely understood but is rooted in the disruption of normal hepatocyte regeneration and homeostasis. Current investigations of post-hepatectomy liver failure and regeneration are focused on evaluation of circulating hepatic function parameters (transaminases, cholestasis, and coagulation parameters), volumetry and hepatic hemodynamics. However, identification of biochemical factors associated with regeneration and post hepatectomy liver failure is crucial for understanding the pathophysiology and identification of patients at risk. The objective of the present systematic review was to identify circulating factors associated with liver regeneration and post hepatectomy liver failure in patients undergoing hepatectomy. The quantitative analysis was intended if studies provided sufficient data. Electronic databases (MEDLINE via PubMed, Web of Knowledge, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on cell signaling factors in liver regeneration and post-hepatectomy liver failure following liver resection in clinical setting. No date restriction was given. No language restriction was used. Studies were assessed using MINORS. This study was registered at PROSPERO (CRD42020165384) prior to data extraction. In total 1953 publications were evaluated for titles and abstracts after exclusion of duplicates. Full texts of 167 studies were further evaluated for inclusion. 26 articles were included in the review and 6 publications were included in the meta-analyses. High levels of serum hyaluronic acid even preoperatively are associated with PHLF but especially increased levels early after resection are predictive of PHLF with high sensitivity and specificity. Postoperative elevation of HA to levels between 100 and 500 ng/ml is increased the risk for PHLF ([OR] = 246.28, 95% [CI]: 11.82 to 5131.83; p = 0.0004) Inteleukin-6 levels show contradicting result in association with organ dysfunction. HGF positively correlates with liver regeneration. Overall, due to heterogeneity, scarcity, observational study design and largely retrospective analysis, the certainty of evidence, assessed with GRADE, is very low. High levels of serum hyaluronic acid show a strong association with PHLF and increased levels after resection are predictive of PHLF with high sensitivity and specificity, even on POD1. Interleukin-6 levels need to be studied further due to contradictive results in association with organ dysfunction. For HGF, no quantitative analysis could be made. Yet, most studies find positive correlation between high HGF levels and regeneration. Prospective studies investigating HGF and other growth factors, hyaluronic acid and interleukins 1 and 6 in correlation with liver regeneration measured sequentially through e.g. volumetry, and liver function parameters, preferably expanding the analysis to include dynamic liver function tests, are needed to sufficiently illustrate the connection between biomolecule levels and clinical outcomes.

Purpose: To establish comparable reporting of surgical results in pediatric liver surgery, the recently introduced composite outcome measures Textbook Outcome (TO) and Comprehensive Complication Index (CCI) are applied and validated in a pediatric surgery context for the first time. In a representative cohort of pediatric patients undergoing liver resection, predictive factors for TO and CCI are investigated, and outcomes are compared to available literature on surgical outcomes of pediatric liver resection.Methods: All liver resections for patients under 21 years of age performed at the Department of General, Visceral, Transplantation and Pediatric Surgery of the University of Heidelberg between 2009 and 2020 were included in the analysis. Criteria for TO were defined prior to the analysis. Univariate and Multivariate regression was applied to identify factors associated with TO and CCI.Results: Fifty-three pediatric patients underwent liver resections during the observation period. No 30- or 90-day mortality occurred. Twenty-three patients (43.4%) had a TO. CCI and TO showed highly significant correlation (b = −30.33, 95% CI [−37.44; −23.22], p < 0.001). Multivariate analyses revealed significant association between intraoperative blood loss (adjusted for circulating blood volume) and CCI (b = 0.70, 95%CI [0.22; 1.32], p = 0.008) and failure to achieve TO (OR = 0.85, 95%CI [0.69; 0.97], p = 0.048).Conclusion: TO and CCI are suited outcome measures in pediatric surgical studies and offer objective comparability of results. Their application in clinical studies will be a major step forward to establish evidence-based therapies in pediatric surgery. Systematic utilization of TO and CCI can aid in generating comparable studies on surgical techniques and outcomes in pediatric liver resection.

Zusammenfassung Einleitung Das Lynch-Syndrom (LS) ist die häufigste Form des erblichen Darmkrebses und verursacht ca. 3 % aller kolorektalen Karzinome (KRK). Ursächlich ist eine pathogene Sequenzvariante in einem Mismatch-Reparaturgen (MLH1, MSH2, MSH6, PMS2, EPCAM). Nach aktueller Schätzung ist ca. eine von 300 Personen Anlageträger für LS (ca. 300 000 Mutationsträger/Deutschland). Anlageträger haben ein erhöhtes Lebenszeitrisiko für ein KRK mit einer kumulativen Inzidenz von 15 bis 46 % bis zum 75. Lebensjahr. Weiterhin ist auch das Risiko für extrakolonische Tumoren wie Endometrium-, Dünndarm-, Magen-, Urothel- und andere Karzinome erhöht. Methoden Das Deutsche Konsortium Familiärer Darmkrebs besteht aus 14 universitären Zentren in Deutschland. Das Ziel des Konsortiums ist es, geeignete Vorsorgeprogramme zu entwickeln und zu evaluieren, damit diese später in die allgemeine Patientenversorgung übernommen werden können. Wir haben aktuell die Empfehlung zur klinischen Betreuung von LS-Patienten überarbeitet. Ergebnis Eine Koloskopie sollte ab dem 25. Lebensjahr alle 12–24 Monate erfolgen. Bei Diagnose eines KRK ist eine onkologische Resektion notwendig, eine Kolektomie mit ileorektaler Anastomose sollte individuell mit dem Patienten besprochen werden. Das Lebenszeitrisiko für ein Magenkarzinom liegt bei 0,2–13 %. Im Rahmen der endoskopischen Überwachung können signifikant mehr Magenkarzinome in früheren Tumorstadien entdeckt werden im Vergleich zur symptomgetriggerten Endoskopie. Das Lebenszeitrisiko für ein Dünndarmkarzinom liegt bei 4–8 %. Dünndarmkarzinome treten zur Hälfte im Duodenum auf, in 10 % der Fälle vor dem 35. Lebensjahr. Eine ÖGD sollte deshalb ab dem 25. Lebensjahr alle 12–36 Monate erfolgen. Schlussfolgerung Die Früherkennung, Vorsorge und Behandlung von kolonischen und extrakolonischen Karzinomen bei Patienten mit LS reduziert die Mortalität und Morbidität, ist aber komplex und in verschiedenen Aspekten noch nicht umfassend evaluiert. Weitere gen- und geschlechtsspezifische Vorsorgeempfehlungen sind wünschenswert und sollen in prospektiven Studien evaluiert werden.

This study aims to examine the health-related quality of life in patients with hepatocellular carcinoma. 181 patients attending a tertiary center outpatient clinic were interviewed and completed the short form 36 (SF36) questionnaire. The SF36 was used to assess health-related QoL. Cross-sectional analyses by group (age, gender, clinical scores, systemic, and local interventions) as well sequel questionnaires were conducted. Participants included were 79% (143/181) men [mean age at first SF36: 63.8 (± 12.3; 18.4–85.8) years]. Barcelona Clinic Liver Cancer (BCLC) stadium C was associated with significantly lower SF36 total scores, and elevated initial alpha-fetoprotein (AFP) concentrations were associated with lower SF36 functional and mental health sum scores throughout the course of the third questionnaire. Patients treated with sorafenib had within the sub-dimension scores a significantly lower result for role limitations due to physical health compared to patients without sorafenib treatment. Patients who underwent a transarterial chemoembolization (TACE) had within the sub-dimension scores a significantly higher result for control of pain compared to patients without TACE. Kaplan–Meier analysis revealed significant survival benefits for patients who underwent any intervention at the first SF36 (mean survival in years 4.3 vs. 1.6; P

Prophylactic drainage after major liver resection remains controversial. This systematic review and meta-analysis evaluate the value of prophylactic drainage after major liver resection. PubMed, Web of Science, and Cochrane Central were searched. Postoperative bile leak, bleeding, interventional drainage, wound infection, total complications, and length of hospital stay were the outcomes of interest. Dichotomous outcomes were presented as odds ratios (OR) and for continuous outcomes, weighted mean differences (MDs) were computed by the inverse variance method. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach, which was mostly moderate for evaluated outcomes. Three randomized controlled trials and five non-randomized trials including 5,050 patients were included. Bile leakage rate was higher in the drain group (OR: 2.32; 95% CI 1.18–4.55; p = 0.01) and interventional drains were inserted more frequently in this group (OR: 1.53; 95% CI 1.11–2.10; p = 0.009). Total complications were higher (OR: 1.71; 95% CI 1.45–2.03; p

Simple Summary Gallbladder cancer (GBC) is an aggressive malignancy with poor prognosis. Currently, therapeutic options are mostly limited to palliative chemotherapy. Considering the advances of immunotherapy, we assessed the expression of the programmed cell death ligand-1 (PD-L1) as the most widely used predictive marker for immunotherapy response in a large Western-world GBC cohort. Additionally, we quantified the expression of the T-cell immunoreceptor with Ig and ITIM domains TIGIT/CD155 axis as an emerging immune checkpoint. Our results indicate that PD-L1 is heterogeneously expressed in Western-world GBC and associated with distinct histomorphological tumor subtypes and increased immune cell densities. We show that a high tumoral PD-L1 expression is a significant negative prognosticator. In a subset of patients, we identified expression of TIGIT in scattered immune cells, which correlated with tumoral expression of its ligand CD155. Our results suggest a subset of GBC patients to be candidates for immunotherapy via (combined) PD-L1 and TIGIT/CD155 inhibition. Abstract Inhibition of the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) axis has opened a new era in the treatment of solid cancers. However, there is no data on the expression and relevance of PD-L1 in Western gallbladder cancer (GBC). We assessed PD-L1 immunohistochemically in 131 GBC patients as Tumor Proportion Score (TPS), Immune Cell Score (IC) and Combined Positivity Score (CPS). Tumor cells expressed PD-L1 in a subset of 14.7% GBC patients at a TPS cut-off of 1%. Higher PD-L1 levels above 10% and 25% TPS were reached in 4.7% and 3.1% of GBC cases, respectively. At a 10% cut-off, TPS was associated with distinct histomorphological subtypes and correlated with poor tumor differentiation. Survival analysis revealed a TPS above 10% to be a highly significant and independent negative prognosticator in GBC. PD-L1 expression was associated with increased CD4+, CD8+ and PD-1+ immune cell densities. In 14.8% of the cases, scattered immune cells expressed T-cell immunoreceptor with Ig and ITIM domains (TIGIT), which was correlated to tumoral expression of its ligand CD155. We here show that a high PD-L1 expression confers a negative prognostic value in Western-world GBC and highlight the TIGIT/CD155 immune checkpoint as a potential new target for GBC immunotherapy.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and features various tumor escape mechanisms from treatment-induced stress. HSP70 plays a critical role in cell protection under stress. eIF4G physiologically regulates the formation of the protein-ribosomal complex and maintains cellular protein synthesis. However, the precise cooperation of both in HCC remains poorly understood. In this study, we demonstrate that HSP70 expression is positively correlated with eIF4G in tumor specimens from 25 HCC patients, in contrast to the adjacent non-tumorous tissues, and that both influence the survival of HCC patients. Mechanistically, this study indicates that HSP70 and eIF4G interact with each other in vitro. We further show that the HSP70-eIF4G interaction contributes to promoting cellular protein synthesis, enhancing cell proliferation, and inhibiting cell apoptosis. Collectively, this study reveals the pivotal role of HSP70-eIF4G interaction as an escape mechanism in HCC. Therefore, modulation of the HSP70-eIF4G interaction might be a potential novel therapeutic target of HCC treatment.

Pancreatoduodenectomy is the standard treatment for pathologies of the pancreatic head and is performed routinely worldwide. The aim of the study was to analyze this procedure in terms of extent of surgery, technical difficulty, and clinical outcomes and thereby provide a standardized surgical categorization of pancreatoduodenectomies for future reference.For this cohort study, all patients who underwent pancreatoduodenectomy at a single center within an 18-year period (October 2001 to December 2019) were identified in a prospectively maintained database. Based on technical difficulty and extent of surgery, 4 pancreatoduodenectomy types were proposed: (1) standard pancreatoduodenectomy; (2) pancreatoduodenectomy with portal vein/superior mesenteric vein resection; (3) pancreatoduodenectomy with multivisceral resection; and (4) pancreatoduodenectomy with arterial resection. Patient characteristics, surgical parameters, and perioperative morbidity and mortality were analyzed. The 4 types were compared with regard to their surgical outcomes.A total of 3,953 pancreatoduodenectomies were performed in the study period. Standard pancreatoduodenectomy (type 1) was the most frequent procedure (n = 2,931, 74.1%), followed by pancreatoduodenectomy with portal vein/superior mesenteric vein resection (type 2: n = 568, 14.4%), pancreatoduodenectomy with multivisceral resection (type 3: n = 415, 10.5%), and pancreatoduodenectomy with arterial resection (type 4: n = 39, 1.0%). Demographic baseline characteristics were clinically comparable among pancreatoduodenectomy types. Mortality within 90-days correlated with the type of pancreatoduodenectomy (type 1: 2.9%; type 2: 4.2%; type 3: 6.3%; type 4: 10.3%; P = .0007). Overall surgical morbidity was 41.7% (type 1), 40.8% (type 2), 52.5% (type 3), and 59.0% (type 4) (P.0001), including postoperative pancreatic fistula type B/C (type 1: 11.9%; type 2: 7.7%; type 3: 14.7%; type 4: 15.4; P = .0031) and delayed gastric emptying (type 1: 19.4%; type 2: 22.5%; type 3: 22.0%; type 4: 25.6%; P = .187) as the most frequent complications. Relaparotomies were more frequent in type 4 (20.5%) and type 3 (20.6%) than in type 2 (12.0%) or type 1 (10.4%) pancreatoduodenectomy (P.0001). Intensive care unit stay ≥2 days was more frequent in type 4 (48.7%) compared with type 3 (25.7%) or type 2 (27.1%) and type 1 (18.6%) (P.0001).The results show different clinical outcomes for the 4 types of pancreatoduodenectomy. Morbidity and mortality correlate with pancreatoduodenectomy type. The proposed pancreatoduodenectomy classification is useful for reporting pancreatoduodenectomy procedures, enhances the comparability of future studies, may be used for training purposes, and may guide intra and postoperative decision-making.

Background: There is little population-based data on hepatocellular carcinoma (HCC) with brain metastases at initial diagnosis published. This study aimed to estimate incidence of brain metastases in initial metastatic HCC and its impact on prognosis.Methods: Newly diagnosed HCC cases from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were screened for the presence of brain metastases. Data were stratified by age and ethnicity. Multivariable logistic and Cox regression were used to identify factors associated with brain metastases and factors associated with overall survival (OS) and cancer-specific survival (CSS), respectively. Kaplan-Meier method and log-rank test were used for survival analysis.Results: 141 cases presenting with brain metastases were identified, accounting for 0.35% of all HCC cases and 2.37% of cases with metastatic HCC disease. The incidence rate was highest among cases with age 50-59 (2.74%), respectively. Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African American patients presented significantly lower disease-specific survival (median time: 1month; interquartile range (IQR):0-3.0 months). Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases (odds ratio (OR) 12.62, 95%CI 8.40-18.97), but not associated with worse OS and CSS among brain metastases cases. Conclusions: The study shows population-based incidence and survival of brain metastases at diagnosis of HCC. Brain metastases are most prevalent in initial metastatic HCC patients with lung or bone metastasis. The results may contribute to consider screening of the brain among HCC with initial lung or bone metastasis.

The aim of this study was to assess and compare the discriminatory performance of well-known risk assessment scores in predicting mortality risk after extended hepatectomy (EH). A series of 250 patients who underwent EH (≥5 segments resection) were evaluated. Aspartate aminotransferase-to-platelet ratio index (APRI), albumin to bilirubin (ALBI) grade, predictive score developed by Breitenstein et al., liver fibrosis (FIB-4) index, and Heidelberg reference lines charting were used to compute cut-off values, and the sensitivity and specificity of each risk assessment score for predicting mortality were also calculated. Major morbidity and 90-day mortality after EH increased with increasing risk scores. APRI (86%), ALBI (86%), Heidelberg score (81%), and FIB-4 index (79%) had the highest sensitivity for 90-day mortality. However, only the FIB-4 index and Heidelberg score had an acceptable specificity (70% and 65%, respectively). A two-stage risk assessment strategy (Heidelberg–FIB-4 model) with a sensitivity of 70% and a specificity 86% for 90-day mortality was proposed. There is no single specific risk assessment score for patients who undergo EH. A two-stage screening strategy using Heidelberg score and FIB-4 index was proposed to predict mortality after major liver resection.

Background Non-alcoholic steatohepatitis (NASH) associated hepatocellular carcinomas (NASH-HCC) are increasing. NASH-HCC often develops in the fibrotic liver. Several analyses report conflicting results regarding the outcome of non-cirrhotic NASH-HCC. Furthermore, type 2 diabetes (T2D) is considered a risk factor for poor survival. The aim of this study was to investigate oncological outcomes of non-cirrhotic NASH-HCC and the impact of T2D. Methods Patients with non-cirrhotic NASH-HCC with T2D as determined by an expert pathologist conducting histological slide review were matched for risks factors for poor outcome (age, gender, body mass index) with patients with NASH-HCC without T2D. These patients were then matched 1:1 with HCCs of other underlying liver diseases with and without T2D. Oncological outcomes were assessed using Kaplan-Meier curves. Results Out of 365 HCCs resected between 2001 and 2017, 34 patients with non-cirrhotic NASH-HCC were selected (17 with T2D, 17 without T2D) and matched with 26 patients with hepatitis-HCC and 28 patients with alcohol-related HCC. Oncological risk factors such as tumor size, resection margin, and vessel invasion were comparable. There was no difference in overall survival (5-year survival 71.3% for NASH-HCC, 60.4% for hepatitis-HCC, 79.9% for alcohol-HCC). NASH-HCC was associated with longer disease-specific survival than hepatitis-HCC (5-year 87.5% vs. 63.7%, p = 0.048), while recurrence-free survival was identical. T2D had no impact on oncological outcomes in either liver disease. Conclusion Non-cirrhotic NASH-HCC has outcomes comparable with other underling etiologies. Despite a lack of cirrhosis, patients with non-cirrhotic NASH-HCC have the same risks of HCC recurrence as patients with cirrhotic liver disease of other etiologies.

SARS-CoV-2 utilizes the ACE2 transmembrane peptidase as essential cellular entry receptor. Several studies have suggested abundant ACE2 expression in the human lung, inferring strong permissiveness to SARS-CoV-2 infection with resultant alveolar damage and lung injury. Against this expectation, we provide evidence that ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation in the human alveolus. Instead, spectral imaging of ex vivo infected human lungs and COVID-19 autopsy samples depicted that alveolar macrophages were frequently positive for SARS-CoV-2, indicating viral phagocytosis. Single-cell transcriptomics of SARS-CoV-2 infected human lung tissue further revealed strong inflammatory and anti-viral activation responses in macrophages and monocytes, comparable to those induced by MERS-CoV, but with virus-specific gene expression profiles. Collectively, our findings indicate that severe lung injury in COVID-19 likely results from an overwhelming immune activation rather than direct viral damage of the alveolar compartment. Funding: ACH, LES, SH were supported by Berlin University Alliance GC2 Global Health (Corona Virus Pre-Exploration Project). ACH, SH, TW and CD were supported by BMBF (RAPID) and ACH, SH by BMBF (alvBarriereCOVID-19). KH, LB, SL, SH, CD, TW, ACH were funded by BMBF (NFN-COVID 19, Organo-Strat). KH, NS, LES, MW, SH, ADG, CD, TW and ACH were supported by DFG (SFB-TR 84). ACH was supported by BIH, Charite 3R, and Charite-Zeiss MultiDim. KH was supported by BMBF (Camo-COVID-19). MW, NS and SH was supported by BMBF (PROVID). MW and NS was supported by BIH and BMBF (SYMPATH, CAPSyS, NAPKON). BO and DB were funded through the BIH Clinical Single Cell Bioinformatics Pipeline. LB was supported by the BMBF (CoIMMUNE), the DFG (KFO 342) and the IZKF of the Medical Faculty of the WWU. Conflict of Interest: The authors declare no competing interests. Ethical Approval: The study was approved by the ethics committee at the Charite clinic (projects EA2/079/13) and Arztekammer Westfalen-Lippe and of the Westfalischen Wilhelms-Universitat (AZ: 2016-265-f-S). Written informed consent was obtained from all patients.

In recent years, the profile for patients undergoing complex liver resections has changed, with mortality rates remaining generally stable. With these factors in mind, the objective of this study was to evaluate the variables associated with surgical outcomes after hepatectomy and identify groups at high risk for postoperative mortality.The records of 1,796 patients who underwent liver resection of more than one liver segment at the Department of General and Transplantation Surgery, University Hospital Heidelberg, Germany, were analyzed. The primary end point was a 90-day in-hospital mortality. Logistic regression analyses were performed to identify risk factors associated with mortality. A risk score was created in accordance with weighted points based on the odds ratios obtained from multivariate logistic regression analyses. External validation of the score was performed, using data derived from 281 patients at the board-certified center for liver surgery in Karlsruhe, Germany.The overall patient morbidity rate (Clavien-Dindo Grade II or greater) was 32%. The 30- and 90-day mortality rates were 3.0% and 4.5%, respectively. In multivariate analysis, factors independently associated with risk for 90-day in-hospital mortality were age ≥60 years (OR 3.71), ASA classification III (OR 2.94), ASA IV (15.66), perihilar cholangiocarcinoma (OR 5.65), intrahepatic cholangiocarcinoma (OR 3.08), INR ≥ 1.1 (OR 2.43), g-GT ≥ 60 U/L (OR 2.86), platelet count ≤ 120/nL (OR 5.52), creatinine ≥ 2 mg/dL (OR 9.85), and right trisectionectomy (OR 2.88). The 90-day mortality-risk score that was created based on these factors effectively stratified patients into very low risk (0-1 points, 0.2% mortality rate in 662 patients), low risk (2-3 points, 2.9% mortality rate in 769 patients), medium risk (4-5 points, 14.7% mortality rate in 232 patients), and high risk (≥6 points, 33% mortality rate in 57 patients) groups (P.0001). As a performance metric, the C-index for the proposed risk score for 90-day mortality was 0.86; whereas external validation revealed that this C-index was 0.89 (P = .0002).Based on patient-related factors and procedure-specific variables, the proposed preoperative-risk score can be used to identify high-risk patients to determine 90-day mortality after liver resection.

Objectives To determine the inpatient management for patients with acute idiopathic facial palsy (IFP) in Thuringia, Germany. Design Population-based study. Setting All inpatients with IFP in all hospitals with departments of otolaryngology and neurology in 2012 in the German federal state Thuringia. Main outcome measures Patients’ characteristics and treatment were compared between departments, and the probability of recovery was tested. Results 291 patients were mainly treated in departments of otolaryngology (55%) and neurology (36%). Corticosteroid treatment was the predominant therapy (84.5%). The probability to receive a facial nerve grading (Odds ratio [OR] =12.939; 95% confidence interval [CI] = 3.599 to 46.516), gustatory testing (OR = 6.878; CI =1.064 to 44.474), and audiometry (OR = 32.505; CI = 1.485 to 711.257) was significantly higher in otolaryngology departments, but lower for cranial CT (OR = 0.192; CI = 0.061 to 0.602), CSF examination (OR = 0.024; CI = 0.006 to 0.102). 131 patients (45%) showed a recovery to House-Brackmann grade ≤II. A pathological stapedial reflex test (Hazard ratio [HR] = 0.416; CI = 0.180 to 0.959) was the only independent diagnostic predictor of worse outcome. Prednisolone dose >500 mg (HR = 0.579; CI 0.400 to 0.838), and no adjuvant physiotherapy (HR = 0.568; CI = 0.407 to 0.794) were treatment-related predictors of worse outcome. Conclusions Inpatient treatment of IFP seems to be highly variable in daily practice, partly depending on the treating discipline, and despite the availability of evidence-based guidelines. The population-based recovery rate was worse than reported in clinical trials. This article is protected by copyright. All rights reserved.

Background: Hepatocellular carcinoma (HCC) has a poor prognosis. Selective internal radiation therapy (SIRT) with microspheres is a treatment option for HCC. This study aimed to assess safety and survival (OS) in patients with HCC treated with SIRT, to stratify patients with tumor vascularization and analyze the impact of sequential sorafenib treatment. Methods: Thirty-nine patients who received SIRT for HCC between 2010 and 2013 at our center were included in this retrospective analysis. Tumor vascularization was assessed using a combination of MRI, MAA-scintigraphy and angiography. Tumor vascularization was correlated with survival. Subgroups are treated with two commercially available 90Y-labeled products SIR-Spheres (n = 16) and TheraSpheres (n = 23) and sequential therapy with sorafenib compared to SIRT only was analyzed. Results: Adverse events occurred in 49% of patients with only four grade 3 and no grade 4 event. Median survival for all patients was 12.5 months (95% CI: 8.7 - 16.3). No significant differences were detectable between Thera Spheres or SIR Spheres. Survival was shorter in patients with low tumor vascularization score (OS: 3.8 months (95% CI 0 - 15.0), p = 0.043). Survival was longer with sorafenib upon progression after SIRT (n=16) with an OS of 17.4 months (95% CI: 12.1 – 22.7) compared to no sorafenib (n = 13; 9.1 months; 95% CI: 3.0 - 15.1) or progression upon sorafenib before SIRT (n = 10; 8.6 months; 95% CI: 5.5 - 11.7). Conclusions: SIRT is safe in HCC patients. Tumor vascularization by radiography and scintigraphy may predict survival benefit. Sorafenib is active after SIRT and significantly prolongs survival.

We present here the design and characterization of a set of spectral calibration beads. These calibration beads are intended for the determination and regular control of the spectral characteristics of fluorescence microscopes and other fluorescence measuring devices for the readout of bead-based assays. This set consists of micrometer-sized polymer beads loaded with dyes from the liquid Calibration Kit Spectral Fluorescence Standards developed and certified by BAM for the wavelength-dependent determination of the spectral responsivity of fluorescence measuring devices like spectrofluorometers. To cover the wavelength region from 400 to 800 nm, two new near-infrared emissive dyes were included, which were spectroscopically characterized in solution and encapsulated in the beads. The resulting set of beads presents the first step towards a new platform of spectral calibration beads for the determination of the spectral characteristics of fluorescence instruments like fluorescence microscopes, FCM setups, and microtiter plate readers, thereby meeting the increasing demand for reliable and comparable fluorescence data especially in strongly regulated areas, e.g., medical diagnostics. This will eventually provide the basis for standardized calibration procedures for imaging systems as an alternative to microchannel slides containing dye solutions previously reported by us. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00216-020-02664-y) contains supplementary material, which is available to authorized users.

Modeling and predicting load courses and HR responses enables individually optimal training control. In HR controlled endurance training, load is expected to gradually decrease to keep HR levels constant due to cardiac drift. This paper analyzes if gender, time under load or progress of training influences characteristics of load controlled by HR in continuous exercise during a long-term training intervention. Nine healthy adults performed a twelve-week training intervention on a bike ergometer. During the Intensive Continuous Method, load was automatically adjusted (ALC) to keep individual HR in the range of 75% HRmax ± 5 bpm.

IntroductionLiver resection is the only curative treatment for primary and secondary hepatic tumours. Improvements in perioperative preparation of patients and new surgical developments have made complex liver resections possible. However, small for size and flow syndrome (SFSF) is still a challenging issue, rendering patients inoperable and causing postoperative morbidity and mortality. Although the role of transhepatic flow in the postoperative outcome has been shown in small partial liver transplantation and experimental studies of SFSF, this has never been studied in the clinical setting following liver resection. The aim of this study is to systematically evaluate transhepatic flow changes following major liver resection and its correlation with postoperative outcomes.Methods and analysisThe TransHEpatic FLOW (THEFLOW) study is a single-centre, non-interventional cohort study, and aims to enrol 50 patients undergoing major hepatectomy (defined as hemihepatectomy or extended hepatectomy based on the Brisbane classification) with or without prior chemotherapy. The portal venous flow, hepatic artery flow and portal venous pressure are measured before and after each resection. All patients are followed-up for 3 months after the operation. During each evaluation, standard clinical data, posthepatectomy liver failure and overall morbidity and mortality will be recorded. THEFLOW study was initiated on 25 March 2018 and is expected to progress for 2 years.Ethics and disseminationThis protocol study received approval from the Ethics Committee of the University of Heidelberg (registration number: S576/2017). The results of this study will be published in a peer-reviewed journal, and will also be presented at medical meetings.Trial registration numberNCT03762876.

The major extended donor criteria (maEDC, steatosis &gt, 40%, age &gt, 65 years, and cold ischemia time &gt, 14 h) influence graft and patient outcomes after liver transplantation. Despite organ shortages, maEDC organs are often considered unsuitable for transplantation. We investigated the outcomes of maEDC organ liver transplantation in patients with hepatocellular carcinoma (HCC). Two hundred and sixty-four HCC liver transplant patients were eligible for analysis. Risk factor analysis was performed for early allograft dysfunction, primary nonfunction, 30-day and 90-day graft failure, and 30-day, 90-day, and 1-year patient mortality. One-year graft survival was higher in recipients of no-maEDC grafts. One-year patient survival did not differ between the recipients of no-maEDC and maEDC organs. The univariate and multivariate analyses revealed no association between maEDC grafts and one-year patient mortality. Graft survival differed between the recipients of no-maEDC and maEDC organs after correcting for a laboratory model of end-stage liver disease (labMELD) score with a cut-off value of 20, but patient survival did not. Patient survival did not differ between recipients who did and did not meet the Milan criteria and who received grafts with and without maEDC. Instead of being discarded, maEDC grafts may expand the organ pool for patients with HCC without impairing patient survival or recurrence-free survival.

Context Studies on the surgical outcome in living kidney donors mainly report perioperative complications with short follow-up. Objective The objectives of this study are to evaluate the long-term surgical outcome in living kidney donors and to identify donors with an increased risk for a complicated postoperative course. Basic Procedures A prospectively collected database of 496 living kidney donors at the Department of General, Visceral, and Transplantation Surgery of the Ruprecht Karls University Heidelberg was retrospectively analyzed in a retrospective, observational single-center study. Results The median follow-up time was 37 months. The perioperative severe complication (Clavien-Dindo IIIb) rate was 2.8%, the early postoperative (PO) severe complication rate (1-3 months post operation) was 0.7%, and the late PO severe complication rate (> 3 months post operation) was 8.4%. In multivariate analyses, male sex was associated with higher overall perioperative complication rate (odds ratio [OR], 1.930; P = .005) as well as higher rate of late PO complications (OR, 2.243; P = .014). An increased body mass index was associated with a higher late and severe (Clavien-Dindo ≥ IIIb) PO complication rate (OR, 1.107; P = .009 and OR, 1.105; P = .008, respectively). Conclusions and Relevance Long-term surgery-associated severe complications occur in 8.4% of kidney donors. Older age is associated with an increased operative time, greater intraoperative blood loss, and longer PO hospital stay. Male donors and donors with an increased body mass index have a higher risk for a complicated PO course after kidney donation. Within a shared decision-making process before living kidney donation, special awareness should be brought to these facts.

BACKGROUND The pre-procurement pancreas suitability score (P-PASS) and the pancreas donor risk index (pDRI) are established predictive scores for graft survival and patient outcome following pancreatic transplantation. This retrospective study aimed to evaluate the predictive value of P-PASS and pDRI following simultaneous pancreas and kidney (SPK) transplantation, or pancreas after kidney (PAK) transplantation, and the clinical impact of donor-specific factors on the postoperative graft and recipient outcome at a single transplant center. MATERIAL AND METHODS The study included 105 patients who underwent SPK (n=104) or PAK (n=4) between 2000 and 2017. Donor-specific and recipient-specific parameters were recorded. Kaplan-Meier analysis and Cox regression analysis were used to assess the outcome after transplantation. RESULTS Overall, the mean 1-year and 5-year pancreas graft survival and patient survival rates were 78.7% and 93.2%, and 76.9% and 90.0%, respectively. The postoperative outcome in patients with a P-PASS score of

Background Two surgical options are available for cystic echinococcosis (CE). The two principal approaches are radical (resection of the cyst) and conservative (evacuation of the cyst content and partial removal of the cyst capsule). Here, we describe a standardized endocystectomy technique for hepatic echinococcosis. Subjects and methods Twenty-one patients (male/female: 4/3; median age: 28 years) with uncomplicated, isolated hepatic CE (cyst stages WHO CE1, 2, 3a, and 3b) that were treated with the standardized endocystectomy described in this paper. Before the operation and during the follow-up period (mean: 33.8 months, median: 24 months), patients underwent clinical and sonographical and/or magnetic resonance imaging assessment during regular visits managed by an interdisciplinary team. Results Forty-seven cysts were treated with the standardized endocystectomy technique. The median number of cysts per patient was two (range: 1–8). Nine patients (43%) had a single cystic lesion. The median operation time was 165 minutes and the median intraoperative bleeding volume was 200 mL. The median hospital stay was nine days (range: 6–28 days). Morbidity (Clavien-Dindo III) occurred in four patients (19%). No mortality and no recurrence were found during the median follow-up time of 24 months. Conclusions The standardized endocystectomy technique presented is a safe procedure with acceptable morbidity, no mortality, and without recurrences in our patient series. Important components of our CE management are interdisciplinary patient care, adequate diagnostic work-ups, and regular pre- and postoperative visits, including long-term follow-up for early and reliable capture of recurrences., Author summary Cystic echinococcosis (CE) is a parasitic disease caused by ingestion of the larval stage of Echinococcus granulosus. The liver is the most commonly infected organ. There are currently four treatments for CE: surgery, percutaneous treatment, medical treatment (benzimidazoles), and watch-and-wait strategy. Treatment is decided based on the WHO cyst staging. The surgical techniques employed depend on the cyst location and related complications (e.g. cyst-biliary fistulas, rupture, and secondary bacterial infection). The two principal surgical approaches are radical (resection of the cyst) and conservative (evacuation of the cyst content and partial removal of the cyst capsule) surgeries. In this study, we presented a conservative surgical approach, a standardized endocystectomy technique, that is suitable for surgical residents. This standardized endocystectomy technique is a safe procedure with acceptable morbidity, no mortality, and without recurrences in our patient series. Important components of CE management are interdisciplinary patient care, adequate diagnostic work-ups, and regular pre- and postoperative visits, including long-term follow-up for early and reliable capture of recurrences.

A 37-year-old male patient with Crohn's disease and multiple liver hemangiomas was referred to our hospital for an atypical hypervascular hepatic lesion detected on an external magnetic resonance imaging (MRI) scan. The patient was otherwise well and had no history of any liver disease. Liver values and tumor markers were normal. Contrast-enhanced ultrasound confirmed multiple hemangiomas in different liver segments and a hypervascular tumor with a hypovascular rim in segment II/IV. Repeat MRI showed a strongly enhancing neoplasm of 2.6 cm with a texture distinctly different from the otherwise relatively uniform hemangiomas, without evidence of interim growth. Ultrasound-guided biopsy revealed a hepatic small vessel neoplasm. Due to the unknown malignant potential, atypical segmental surgical resection was performed. Final histopathological analysis confirmed the complete resection of the lesion. The postoperative course was uneventful.Ein 37-jähriger M.-Crohn-Patient mit bekannten Leberhämangiomen wurde uns zur weiteren Abklärung einer unklaren, unscharf begrenzten Leberläsion zugewiesen. Vorerkrankungen der Leber bestanden nicht. Die Leberwerte und Tumormarker waren unauffällig. Ein Kontrastmittelultraschall bestätigte mehrere Hämangiome in der Leber und charakterisierte die Läsion in Segment II/IV als hypervaskularisiert mit einem hypovaskulären Randsaum. Das wiederholte MRT zeigte einen stark Kontrastmittel aufnehmenden 2,6 cm großen Tumor, der sich in der Textur deutlich von den ansonsten uniform aussehenden Hämangiomen unterschied und kein zwischenzeitliches Wachstum aufwies. Die sonografisch gesteuerte Biopsie ergab eine Gefäßneoplasie (“hepatic small vessel neoplasm”). Aufgrund der unbekannten Entartungstendenz dieser Entität wurde eine atypische Segmentresektion durchgeführt. Die endgültige Histopathologie bestätigte die Diagnose der vorherigen Biopsie und die vollständige Entfernung der Läsion. Der postoperative Verlauf war komplikationslos.

Background Primary Hepatic Epithelioid Hemangioendothelioma is an extremely rare tumor of vascular origin. Patients In this work we present clinical data and long term results of eight patients who were surgically treated in our institution. Liver transplantation was performed in five patients (four cadaveric and one living related) and major liver resection in three patients. Three patients are alive with recurrent tumor. After a median follow-up of 100 months (48–266) all patients are alive. Conclusions Only surgery can provide cure in HEH. If the extent of the disease prohibits primary resection liver transplantation might offer the most valuable option., Highlights • Primary Hepatic Epithelioid Hemangioendothelioma is an extremely rare tumor of vascular origin. In this work we present clinical data and long term results of eight patients who were surgically treated in our institution. • Liver transplantation was performed in five patients (four cadaveric and one living related) and major liver resection in three patients. After a median follow up of 100 months (48–266) all eight patients are alive. During follow up, three patients developed recurrent tumor, one in the lung and the liver, one only in the liver, and one patient developed systemic metastases.

Purpose A systematic review was performed to evaluate the effect of preoperative biliary drainage (PBD) on outcomes after liver resection in perihilar cholangiocarcinoma (PHCC) patients. Method MEDLINE and Web of Science were searched up to March 2019. All studies assessing morbidity, mortality, or recurrence in patients who received PBD and hepatectomy for PHCC were included. Mantel–Haenszel tests with a random-effects model were used for meta-analysis. Results Sixteen studies involving 2162 patients were included. PBD was associated with higher major morbidity odds ratio [OR] = 1.51; 95 % confidence interval [CI] = 1.14–2.00). Selecting patients for PBD based on simple selection criteria was associated with significantly higher major morbidity (OR = 1.57; 95 % CI = 1.10–2.25). In contrast, selecting patients for PBD according to strict criteria resulted in lower major morbidity compared with patients without PBD (OR = 0.51; 95 % CI = 0.18–1.42). PBD did not influence mortality (OR = 1.06; 95 % CI = 0.70–1.61). Tumor recurrence was significantly higher in the PBD group (OR = 2.07; 95 % CI = 1.38–3.11). To decrease PBD-related complications, the duration between PBD and hepatectomy should be shorter than two weeks. Most reports described PBD on the future liver remnant side. Conclusions Routine PBD cannot be recommended but it may be useful in highly selected patients suffering from cholangitis, malnutrition, and long lasting jaundice, for whom an extended hepatectomy is planned. However, However, routine PBD cannot be recommended due to higher morbidity rate after hepatectomy clear patient selection criteria can be defined for PBD in future multicenter randomized controlled studies.

Individuals affected with autosomal recessive cutis laxa type 2B and 3 usually show translucent skin with visible veins and abnormal elastic fibers, intrauterine and/or postnatal growth restriction and a typical triangular facial gestalt. Here we describe three unrelated individuals in whom such a cutis laxa syndrome was suspected, especially after electron microscopy revealed immature and less dense dermal elastic fibers in one of them. However, one of these children also displayed optic atrophy and two hypogammaglobulinemia. All had elevated liver enzymes and acute liver failure during febrile episodes leading to early demise in two of them. The only surviving patient had been treated with immunoglobulins. Through exome sequencing we identified mutations in NBAS, coding for a protein involved in Golgi-to-ER transport. NBAS deficiency causes several rare conditions ranging from isolated recurrent acute liver failure to a multisystem disorder mainly characterized by short stature, optic nerve atrophy and Pelger-Huet anomaly (SOPH). Since we subsequently verified Pelger-Huet anomaly in two of the patients the diagnosis SOPH syndrome was unequivocally proven. Our data show that SOPH syndrome can be regarded as a differential diagnosis for the progeroid forms of cutis laxa in early infancy and that possibly treatment of the hypogammaglobulinemia can be of high relevance for the prognosis.

There are diverse approaches to parenchymal transection and the preferred approach remains controversial among liver surgeons. Stapling devices, which were initially established for vascular control, have been the standard parenchymal transection technique in many departments for more than 15 years. This article describes the technical aspects, tips, and tricks of stapled hepatectomy using right hemihepatectomy as an example. The existing literature on this topic is also reviewed.

BackgroundDelirium affects 25% of older inpatients and is associated with long-term cognitive impairment and future dementia. However, no population studies have systematically ascertained cognitive function before, cognitive deficits during, and cognitive impairment after delirium. Therefore, there is a need to address the following question: does delirium, and its features (including severity, duration, and presumed aetiologies), predict long-term cognitive impairment, independent of cognitive impairment at baseline?MethodsThe Delirium and Population Health Informatics Cohort (DELPHIC) study is an observational population-based cohort study based in the London Borough of Camden. It is recruiting 2000 individuals aged ≥70 years and prospectively following them for two years, including daily ascertainment of all inpatient episodes for delirium. Daily inpatient assessments include the Memorial Delirium Assessment Scale, the Observational Scale for Level of Arousal, and the Hierarchical Assessment of Balance and Mobility. Data on delirium aetiology is also collected. The primary outcome is the change in the modified Telephone Interview for Cognitive Status at two years.DiscussionDELPHIC is the first population sample to assess older persons before, during and after hospitalisation. The cumulative incidence of delirium in the general population aged ≥70 will be described. DELPHIC offers the opportunity to quantify the impact of delirium on cognitive and functional outcomes. Overall, DELPHIC will provide a real-time public health observatory whereby information from primary, secondary, intermediate and social care can be integrated to understand how acute illness is linked to health and social care outcomes.

Background. It is a novel idea that platelet counts may be associated with postoperative outcome following liver surgery. This may help in planning an extended hepatectomy (EH), which is a surgical procedure with high morbidity and mortality. Aim. The aim of this study was to evaluate the predictive potential of platelet counts on the outcome of EH in patients without portal hypertension, splenomegaly, or cirrhosis. Methods. A series of 213 consecutive patients underwent EH (resection of ≥ five liver segments) between 2001 and 2016. The association of preoperative platelet counts with posthepatectomy liver failure (PHLF), morbidity (based on Clavien-Dindo classification), and 30-day mortality was evaluated using multivariate analysis. Results. PHLF was detected in 26.3% of patients, major complications in 26.8%, and 30-day mortality in 11.3% of patients. Multivariate analysis revealed that the preoperative platelet count is an independent predictor of PHLF (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.3–15.0, p=0.020) and 30-day mortality (OR 4.4, 95% CI 1.1–18.8, p=0.043). Conclusions. Preoperative platelet count is associated with PHLF and mortality following extended liver resection. This association was independent of other related parameters. Prospective studies are needed to evaluate the predictive role and to determine the impact of preoperative correction of platelet count on postoperative outcomes after EH.

BackgroundBenign liver tumours represent a challenge in clinical management. There is considerable controversy with respect to the indications for surgery as the evidence for surgical treatment is variable. The aim of this retrospective study was to analyse the indication and outcome after resection of benign, solid liver lesions.MethodsData of 79 patients, who underwent liver resection between 2001 and 2012, were analysed for demographic and outcome parameters.ResultsThirty‐eight patients with focal nodular hyperplasia (48%), 23 patients with haemangioma (29%) and 18 patients with hepatocellular adenoma (23%) underwent a hepatic resection. A major hepatic resection was performed in 23 patients (29%) and a minor resection in 56 patients (71%). The post‐operative mortality rate was zero and the 30‐day morbidity rate 13.9%. After a median follow‐up of 64 months, 75 patients (95%) were alive, and no patient had developed recurrent disease. Fifty‐four patients (68%) were pre‐operatively symptomatic, of which, 87% had complete or partial relief of symptoms after a liver resection. The incidence of symptoms increased with the lesions' size.DiscussionThe management of benign liver lesions necessitates an individualized therapy within a multidisciplinary, evidence‐based, treatment algorithm. Resection of benign liver lesions can be performed safely in well‐selected patients without mortality and low post‐operative morbidity.

Discussions about the benefit of liver resection (LRx) for non-colorectal, non-neuroendocrine metastases are controversial. This study aimed to analyze the outcome of LRx for these patients and validate a previously published prognostic risk model. The study analyzed 150 patients who underwent LRx for non-colorectal non-neuroendocrine (NCNN) metastases. Patients’ demographics, tumor characteristics, treatment options, and postoperative outcome were investigated. The Kaplan–Meier method and Cox regression models were used to assess survival and prognostic variables. After a median follow-up period of 61 months, 39 % of the patients were alive. The 30-day mortality rate was 0.7 %. The overall, disease-free, and intrahepatic recurrence-free survival rates were respectively 42, 29, and 51 % at 5 years and 28, 23, and 47 % at 10 years. The negative prognostic factors identified in the multivariate analysis were melanoma (p = 0.04), squamous tumors (p = 0.01), and a primary tumor liver metastasis, with an interval shorter than 2 years (p = 0.02), whereas the predictive prognostic factors identified were breast cancer (p = 0.04), stromal tumors (p = 0.03), and major LRx (p = 0.04). The prognostic risk score stratified patients into low risk (0–3 points: n = 50; 5-year overall survival [OS] 58 %), medium risk (4–6 points: n = 91; 5-year OS 35 %), and high risk (≥7 points: n = 9; 5-year OS, 33 %) groups (p = 0.01). Liver resection for patients with NCNN metastases is a safe treatment option. More than 25 % of patients can achieve a long-term survival of 10 years when the histology of the primary tumor and the surrogates for the individual biologic tumor behavior are taken into account. Exclusion of patients with NCNN liver metastases from surgical therapy is no longer justified.

The development of a lanthanum-phosphate glass doped with several rare-earth-ions for use as solid fluorescence standard is described. The cuvette-shaped reference material which shows a characteristic emission intensity pattern upon excitation at 365 nm consisting of a multitude of relatively narrow emission bands in the wavelength region between 450 and 700 nm is intended for the day-to-day performance validation of fluorescence measuring devices. Evaluation of the fluorescent glass includes the determination of all properties which can affect its relative emission intensity profile or contribute to the uncertainty of the certified values like absorption spectra, fluorescence anisotropy, excitation wavelength, and temperature dependence of the spectroscopic features, homogeneity of fluorophore distribution, and photo- and long-term stability. Moreover, a certification procedure was developed including the normalization of the intensity profile consisting of several narrow emission bands and the calculation of wavelength-dependent uncertainties. Criteria for the design, characterization, and working principle of the new reference material BAM-F012 are presented, and possible applications of this ready-to-use fluorescence standard are discussed.