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Background: Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. Methods: Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). Results: Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P=0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P<0.001). Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC (mean overall survival 6.2 versus 6.6 years respectively; P=0.030). Conclusion: Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival. Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria.

Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). Summary and Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov:NCT00355862), the effect of sirolimus on the recurrence of HCC after LTwas investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. Patients and Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. Results: Sirolimus use for >= 3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) >= 10 ng/mL and having used sirolimus for >= 3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49- 0.59, P = 0.0079- 0.0245). Conclusions: mTOR-inhibitor treatment with sirolimus for >= 3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. Clinical Trial Registration: EudraCT: 2005-005362-36 Clinicaltrials.gov: NCT00355862.

Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV+ subgroup of patients from the randomized controlled, international SiLVER Study. We performed a post hoc analysis of 166 HCV+ SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A: n = 88) received mTOR inhibitor (mTORi)-free, calcineurin inhibitor (CNI)-based versus sirolimus-based immunosuppression (group B: n = 78). We found no significant difference regarding HCV-RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus-based immunosuppression + CNIs for >50% (B1; n = 44) or <50% (B2; n = 34) of the time. While there remained no difference in HCV-RNA titer between groups, HCC recurrence-free survival in group B1 (81.8%) was markedly better versus both group A (62.7%; P = 0.0136) and group B2 (64.7%; P = 0.0326); Interestingly, further subgroup analysis revealed an increase (P = 0.0012) in liver enzyme values in group B2. Taken together, in HCV-infected patients with HCC and LTx, mTORi immunosuppression + CNIs yields excellent outcomes. Unexpectedly, higher levels of liver inflammation and poorer outcomes occur with mTORi monotherapy in the HCV+ subgroup.

Background: The corona pandemic is changing the framework conditions for medical studies and continuing education as well as the work with patients and within teams. Systematic reflection and communication about experiences and ways of dealing with them forms the basis for successful learning in and out of the crisis. Therefore, we designed a 90-minute workshop "Corona-Debriefing" for students and physicians in specialist-training in family medicine (ÄiW) using three successive moderated interaction phases: Questionnaire survey via tele-dialogue voting (TED) with immediate presentation of results and discussion, moderated experience reports on the categories risk/assessment/support/coping and finally moderated group discussions in small groups to collect "best practice" examples of crisis management. Objective: We tested "Corona-Debriefing" as a pilot test with 48 participants (TN) in July 2020 (30 present, 14 online) in order to assess mental stress and risk perception of participants plus formative/brief summative evaluation of the workshop. Methods: The PHQ-4 with its subscales GAD-2 (anxiety) and PHQ-2 (depression) was used to assess mental stress; risk assessments were made by means of self-constructed 5-point Likert-scales for the dimensions person/society/health/economy. A formative evaluation was carried out by means of a questionnaire at the end of the event; the brief summative assessment was asked for by means of a school grading scale. Results: 37 complete TED questionnaires and 22 evaluations were obtained. TN showed a low personal risk assessment, but considerable fears about social and economic developments. Needs are seen mainly in improvements regarding organization, protective equipment and technical communication (e.g. official recommendations for action). The workshop was rated "good" or "very good" in 95% of the evaluations. Criticism was directed at the limited time available, the narrowing of topics by moderators and the desire for (even) more, Hintergrund: Die Corona-Pandemie verändert die Rahmenbedingungen von Studium und Weiterbildung in der Medizin ebenso wie die Arbeit am Patienten und im Team. Eine systematische Reflektion und Kommunikation über Erfahrungen und Umgangsweisen bildet die Grundlage für ein erfolgreiches Lernen in und aus der Krise. Wir konzipierten daher einen 90-Minuten Workshop "Corona-Debriefing" für Studierende und Ärzt*innen in Weiterbildung (ÄiW) mittels drei aufeinanderfolgenden moderierten Interaktionsphasen: Fragebogenerhebung per Tele-Dialog-Voting (TED) mit unmittelbarer Ergebnisvorstellung und Diskussion, moderierte Erlebnisberichte zu den Kategorien Gefährdung / Bewertung / Unterstützung / Bewältigung und schließlich moderierte Gruppendiskussionen in Kleingruppen zur Sammlung von "Best-Practice" - Beispielen zur Krisenbewältigung. Ziele: Wir erprobten "Corona-Debriefing" als Pilottest mit 48 ÄiW als Teilnehmern (TN) im Juli 2020 (30 präsent, 14 online) mit den Auswertungszielen psychische Belastung / Gefährdungseinschätzung der TN, inhaltliche Schwerpunkte, technische Umsetzung, Gesamtbewertung und Kritik am Format. Methoden: Zur Erfassung der psychischen Belastung diente der PHQ-4 mit seinen Subskalen GAD-2 (Ängstlichkeit) und PHQ-2 (Depressivität); Gefährdungseinschätzungen wurden mit selbstkonstruierten 5-Punkt-Likert-Skalen zu den Dimensionen Person/Gesellschaft/Gesundheit/Ökonomie erhoben. Eine formative und Evaluation erfolgte mittels Fragebogen am Veranstaltungsende, die Gesamtbewertung wurde mittels Schulnotenskala erfragt. Ergebnisse: Ausgewertet werden konnten 37 komplette TED-Fragebögen und 22 Evaluationen. TN zeigten eine geringe persönliche Gefährdungseinschätzung, jedoch erhebliche Befürchtungen zu gesellschaftlichen und ökonomischen Entwicklungen. Bedarfe werden v.a. in Organisation, Schutzausrüstung und fachlicher Kommunikation (z.B. offiziellen Handlungsempfehlungen) gesehen. Der Workshop wurde in 95% der Evaluationen "gut" oder "sehr gut" bewertet. Kritik

Background.We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods. In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-To-Treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results. Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most fromsirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions. Sirolimus in LTx recipients with HCC does not improve long-Term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

Background: Primary health care in rural regions is currently undergoing a global crisis in respect of the next generation of practitioners. National and international recommendations advise placing greater emphasis upon practical skills and competences in medical studies. It is also in the interest of training the next generation to include mentoring and longitudinal integration of contact to teaching practices for general medicine in an early stage. Consequently, the General Practice Class (KAM) was introduced in Halle in 2011 as an elective with 20 individually mentored students per year, beginning with the first subject-related semester. We are now reporting on the results of the evaluation for the first two years. Method: A standardised online survey was carried out with all students who took part in the KAM in the two years 2011 and 2012 (N=38). For both years the survey was made at the end of the first summer semester on the basis of an adapted version of the Heidelberger Inventar zur Lehrevaluation (Heidelberg Inventory for the Evaluation of Teaching, HILVE-II) and the Berliner Evaluationsinstrument für selbsteingeschätzte, studentische Kompetenzen (Berlin Evaluation Instrument for the self-assessment of student competences, BEvaKomp) . Furthermore, each year the preference for the choice of specialty and location of a medical practice was queried. Predictors for the preference of the chosen specialty and the location of a medical practice were estimated by binary logistic regression analysis. Via univariate evaluations the number of students who reported an increase in knowledge in different areas of competence as a result of the KAM was counted. Correlations between the intention to remain in the KAM and the quality of teaching were evaluated on the basis of bivariate correlations. Results: 48% of the students agreed partly or fully that the KAM seminars enhanced their specialist competence. This individual acquiring of competence in the model project repr, Hintergrund: Die medizinische Grundversorgung in ländlichen Regionen befindet sich weltweit in einer Nachwuchskrise. Internationale und nationale Empfehlungen raten zur Stärkung praktischer Fertigkeiten und Kompetenzen im Medizinstudium. Dazu gehört, auch im Interesse der Nachwuchsbindung, den Kontakt zu allgemeinmedizinischen Lehrpraxen frühzeitig, mentoriert und longitudinal zu integrieren. Dazu wird die Klasse Allgemeinmedizin (KAM) in Halle seit 2011 als Wahlpflichtfach mit 20 individuell mentorierten Studierenden pro Jahr beginnend mit dem ersten Fachsemester durchgeführt. Wir berichten über die Evaluationsergebnisse der ersten zwei Jahre.Methodik: Eine standardisierte Online-Befragung wurde mit allen Teilnehmern der KAM in zwei Jahrgängen 2011 bis 2012 (N=38) durchgeführt. Die Befragung erfolgte jeweils zum Ende des ersten Sommersemesters und nutzte eine adaptierte Version des Heidelberger Inventars zur Lehrevaluation (HILVE-II) und das Berliner Evaluationsinstrument für selbsteingeschätzte, studentische Kompetenzen (BEvaKomp). Ferner wurde jährlich die Präferenz zu Fachgebietswahl und Ort der Niederlassung erfragt. Mittels binär-logistischer Regression wurden Prädiktoren für die Präferenz zur Fachgebietswahl Allgemeinmedizin und Ort der Niederlassung geschätzt. Durch univariate Auswertungen wurden die Anteile der Studierenden ausgezählt, die in verschiedenen Kompetenzbereichen einen Wissenszuwachs durch die KAM berichteten. Zusammenhänge zwischen den beabsichtigten Verbleib in der KAM und der Lehrqualität wurden anhand bivariater Korrelationen ausgewertet. Ergebnisse: 48% der Studierenden stimmten der Aussage eher oder völlig zu, dass die Seminare der KAM bei ihnen zu einer Steigerung der Fachkompetenz geführt haben. Dieser individuelle Kompetenzerwerb im Modellprojekt stellte einen signifikanten Prädiktor für die Präferenz zur Fachgebietswahl Allgemeinmedizin dar (OR 7,98; 95%-KI [1,27-50,27], p= 0,027). Studierende, die das Engagement (r=0,504), die Betreuu

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between “high-” and “low-benefit” patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors (“no-benefit group”; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor (“large-benefit group”; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months. Conclusion: The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910–1919).