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Context The LMU University Hospital is among the largest healthcare facilities in Germany. The measures implemented prior to and during the first pandemic wave of COVID-19, were evaluated in preparation of a second pandemic wave. This paper presents the pandemic management concept, evaluation and adaptation of LMU University Hospital. Methods Between July and September 2020 the disaster management team of LMU University Hospital conducted a mixed-method evaluation of the hospital’s pandemic management. A workshop series based on the After Action Review working group format was organized to examine the management structure, decision-making processes, documentation, and crisis preparedness response for a second COVID-19 wave. Further, the satisfaction of employees with the hospital’s COVID-19 management was examined through an anonymous survey. Results The workshop series highlighted a need for structural and operational adaptation of the COVID-19 management at LMU University Hospital. The results of the employee survey ( N = 2182) provided positive feedback for the measures taken during the first pandemic wave. Specific actions were derived concerning the availability of personal protective equipment and emergency childcare services. A key outcome of both evaluation activities was the identified need for further improvement in communication between stakeholders. All changes were adopted prior to the second pandemic wave.

PDF file - 68K, S5. Methylation of Sox9-promoter, Sox9 and VEGF expression in patient samples.

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PDF file - 70K, S2. A) Differential methylation of the Sox9-promoter in NMET and HMET cells. B) Methylation and hypoxia. NMET and HMET cells were cultivated under hypoxia or normoxia, respectively. (C) Effect of methylation inhibition on VEGF expression. Relative transcription of VEGF in LMET and HMET cells is demonstrated. D) Effect of methylation inhibition on Sox9 expression.

PDF file - 130K, Supplemental Table 1. Differential expression of the genes associated to cancer relevant pathways.

PDF file - 50K, S4. Sox9 does not influence stability of HIF1alpha.

Freshly isolated human hepatocytes are an important model for translational research, validation of experiments done in animals, and preclinical studies. Human hepatocyte isolation often cannot be carried out easily on demand in common research laboratories, and researchers often collaborate to share hepatocytes or outsource hepatocyte isolations. As a prerequisite for such a strategy, hepatocytes have to maintain their phenotypes after transport. Therefore, this study aimed to determine if overnight storage or shipment of hepatocytes affects their quality when viability, adherence, and cytochrome P450 (CYP) activities are considered. Hepatocytes were stored overnight or shipped to a collaborator in a cold storage solution on wet ice. On the next day, viability of hepatocytes was assessed before plating the cells to determine adherence. Hepatocytes were also cultured in a sandwich culture to determine CYP activities and inducibility. The results showed that although viability (79% ± 0.7% on isolation) was significantly decreased by overnight storage or shipment by 11% (

ZusammenfassungHintergrundDie COVID-19-Pandemie hat seit ihrem Beginn zu einem erhöhten psychosozialen Unterstützungsbedarf bei Patient*innen, Angehörigen und Mitarbeiter*innen geführt und übliche Wege klinischer Versorgung erschwert. Sowohl Quarantäne- und Isolationsmaßnahmen als auch SARS-CoV-2-Infektionen und -Erkrankungen sind zu neuen und erheblichen Belastungsfaktoren geworden, die in neuen Ansätzen der Versorgung adressiert werden müssen.Ziel der Arbeit und MethodeDieser Beitrag beschreibt die Entwicklung des KonzeptesPsychosoziale Versorgung COVID-19am LMU-Klinikum in München durch ein interdisziplinäres Team von Psychiater*innen, Psycholog*innen, Seelsorger*innen, Psychoonkolog*innen und Palliativmediziner*innen.ErgebnisDas neue Versorgungsmodell zur psychosozialen Unterstützung wurde für stationäre COVID-19-Patient*innen des Klinikums, deren Angehörige und Mitarbeiter*innen bestehend aus fünf Elementen implementiert.DiskussionDas Angebot integriert innovative und nachhaltige Ansätze, wie den Einsatz telemedizinischer Interventionen, und unterstreicht den Wert interdisziplinärer Zusammenarbeit zur Bewältigung von Herausforderungen im Gesundheitswesen.

Einfuhrung Die Medizin und damit auch die Chirurgie waren fur den Patienten noch nie so sicher und nachvollziehbar wie heute. Trotzdem gewinnt man aus der offentlichen Diskussion den Eindruck, dass Komplikations- und Fehlerhaufigkeit zunehmen und dass dabei die chirurgischen Facher mit ca. drei Viertel aller Vorwurfe uber Behandlungsfehler ganz im Vordergrund stehen. Dies hat wesentlich mit der leichtfertigen Verknupfung der Begriffe Komplikation und Fehler, aber auch mit unterschiedlichen Betrachtungsweisen von Patienten, Arzten und Juristen zu tun. Mit unserer arztlichen Tatigkeit sind obligat auch Komplikationen verbunden. Sie durfen weder beschonigt noch negiert werden. Die Minimierung des Komplikationsrisikos einerseits, die rasche Erkennung und der sorgfaltige Umgang mit der eingetretenen Komplikation andererseits machen (auch) eine gute Chirurgie aus. Davon handelt dieses Kapitel, denn oft ist nicht die Komplikation das Problem, sondern der Umgang mit ihr. Zunachst muss aber erlautert werden, wie eine Komplikation definiert ist, wie Komplikation und Fehler zusammenhangen, was unter unvermeidbar bzw. schicksalshaft und was unter vermeidbare Fehlerfolge zu verstehen ist.

Neben eigenen Erkrankungen (Abszess, Hernie) hat die Bauchdecke vor allem Bedeutung als Zugangsweg fur die chirurgische Behandlung von Erkrankungen der intraabdominellen Organe. Der Zugang kann dabei primar als Laparotomie, d. h. konventionell offen, oder als Laparoskopie erfolgen. Dieses Kapitel erlautert die wichtigsten Laparotomieformen sowie das Vorgehen beim postoperativen Bauchdeckenverschluss.

Die Chirurgie ist das Gebiet der Medizin, das Storungen und Veranderungen der Organe mittels operativer Eingriffe behandelt. Ein Chirurg, nach der griechischen Wortwurzel „der mit der Hand arbeitende“, wird Chirurg, weil ihn die manuelle Tatigkeit des Operierens in Kombination mit seiner Aufgabe als ganzheitlich handelnder Arzt und seiner naturwissenschaftlichen Grundhaltung fasziniert. Oder wie es FC Spencer formuliert hat: „Surgical competence combines the intellectual excercise of decision making with the ability to perform mechanical tasks.“

Einfuhrung Eine Operation ist ein zu diagnostischen oder Heilzwecken vorgenommener Eingriff in einen lebenden Organismus, i. e. S. der bei strenger Indikation kunstgerecht auszufuhrende fachorientierte Eingriff in den menschlichen Korper und damit in die korperliche Integritat. So verschiedenartig die Operationstaktiken und -techniken in den chirurgischen Fachern und Subspezialitaten auch sind, so haben sie doch alle die gleichen Grundvoraussetzungen zu erfullen: eine korrekte Indikationsstellung, eine Einwilligung des Patienten, eine Risikobewertung, eine sorgfaltige Durchfuhrung des Eingriffes selbst und eine postoperativen Nachbetreuung. Eine Operation i. e. S. beginnt mit der Durchtrennung und endet mit der Vereinigung von Geweben. Dazwischen liegt die Verwirklichung der Zielvorstellung fur die Operation, die schematisch in der Entfernung von Geweben (Beispiel Amputation, Tumorresektion), der Zusammenfuhrung von Geweben (Beispiel Anastomose, Bypass, Osteosynthese), der Korrektur von Geweben (Beispiel Narbenkorrektur, Umstellungsosteotomie) oder dem Ersatz von Geweben (Beispiel plastischer Gewebetransfer, Transplantation) oder Kombinationen davon besteht.

Hepatocytes differentiated from induced pluripotent stem cells or stem cells have the potential to be representative in vitro models of the human liver for research as well as early safety assessment programs. However, up until now, there has been no definitive proof that differentiated hepatocytes recapitulate the phenotype and functional characteristics of primary hepatocytes from the same individual. Thus, a method for the concurrent isolation of hepatocytes and hepatic stem cells is presented here to provide the cells necessary for the evaluation of the required benchmarking. The method presented here generated high-quality hepatocytes with a purity of 94 ± 1% and a high percentage viability of 79 ± 2%. Furthermore, the hepatic stem cells isolated were found to be actively proliferating and have a purity of 98 ± 1%. Thus, these isolated cells can be used as a powerful tool for the validation of differentiated hepatocyte in vitro models.

More than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-specific pattern of metastasis in 1889, now known as the "seed and soil" theory where distinct cancer types are found to metastasize to different tumor-specific sites. Our understanding of the biology of tumor metastasis and specifically the molecular mechanisms driving their formation are still limited, in particular, as it relates to the genesis of oligometastasis. In the following review, we discuss recent advances in general understanding of this metastatic behavior including the role of specific signaling pathways, various molecular features and biomarkers, as well as the interaction of carcinoma cells with their tissue microenvironments (both primary and metastatic niches). The unique features that underlie OMD provide potential targets for localized therapy. As it relates to clinical practice, OMD is emerging as treatable with surgical resection and/or other local therapy options. Strategies currently being applied in the clinical management of OMD will be discussed including surgical, radiation-based therapy, ablation procedures, and the results of emerging clinical trials involving immunotherapy.

ZusammenfassungDie Notfallversorgung in den deutschen Krankenhaus-Notaufnahmen ist kaum erforscht. Anlässlich der Restrukturierung des Städtischen Klinikums München initiierte der Stadtrat den „Runden Tisch Notfallversorgung“ um Richtzahlen für die Kapazitätsplanung zu erhalten. Die vorliegende Studie sollte dazu Behandlungsdaten von 14, an der Notfallversorgung hauptsächlich beteiligten, Krankenhausnotaufnahmen analysieren. Für stationäre Fälle wurden Daten nach §21 Krankenhausentgeltgesetz, für ambulante Fälle – soweit verfügbar – ähnliche Daten herangezogen, anonymisiert und mit Rettungsdienstdaten zusammengeführt. Um die Bereiche Behandlungsdringlichkeit, diagnostischer/therapeutischer Aufwand und Bettenbedarf beschreiben zu können wurden die Daten jeweils in einem vierstufigen System kategorisiert. Aus 12 Monaten wurden 524 716 Behandlungsfälle erfasst: 34% wurden stationär aufgenommen, 80% kamen ohne zu Hilfenahme des Rettungsdienstes. Jeder siebte Patient, der selbstständig eine Notaufnahme aufsuchte, benötigte ein Intensiv- oder Überwachungsbett (ICU/IMC). Pro Tag und 100 000 Einwohner stellten sich 64 Fälle mit einem Bettenbedarf von 7 ICU/IMC und 15 Normalstationsbetten vor. Die meisten Fälle (66%) wurden ambulant behandelt und kamen zu Zeiten, in denen kassenärztliche Notfallversorgungseinrichtungen erreichbar wären. Die Dringlichkeit dieser Fälle war meist gering (50,9%), der Aufwand oft aber hoch, begründet durch Diagnostik und chirurgische Versorgungen. Die Studie liefert Grundlagen zur Planung der Notfallversorgung. Ein Großteil der Vorstellungen scheint insbesondere bei Verletzungen und bei Krankheitsbildern, die einer differenzierten Abklärung bedürfen, medizinisch gerechtfertigt weshalb entsprechende Kapazitäten eingeplant werden müssen. Die Studie zeigt auch, dass eine Kapazitätsplanung allein auf der Basis der rettungsdienstlich vorgestellten Fälle eine ungeeignete, weil einseitige Betrachtungsweise ist.

Since the beginning of the outbreak, the COVID-19 pandemic has caused an increased demand for psychosocial support for patients, their family members, and healthcare workers. Concurrently, possibilities to provide this support have been hindered. Quarantine, social isolation, and SARS-CoV‑2 infections represent new and severe stressors that have to be addressed with innovative psychosocial care.This article describes the COVID-19 psychosocial first aid concept at the University Hospital Munich (LMU Klinikum) developed by an interdisciplinary team of psychiatric, psychological, spiritual care, psycho-oncological, and palliative care specialists.A new psychosocial first aid model has been implemented for COVID-19 inpatients, family members, and hospital staff consisting of five elements.The concept integrates innovative and sustainable ideas, e.g. telemedicine-based approaches and highlights the importance of multidisciplinary collaboration to cope with challenges in the healthcare system.HINTERGRUND: Die COVID-19-Pandemie hat seit ihrem Beginn zu einem erhöhten psychosozialen Unterstützungsbedarf bei Patient*innen, Angehörigen und Mitarbeiter*innen geführt und übliche Wege klinischer Versorgung erschwert. Sowohl Quarantäne- und Isolationsmaßnahmen als auch SARS-CoV-2-Infektionen und -Erkrankungen sind zu neuen und erheblichen Belastungsfaktoren geworden, die in neuen Ansätzen der Versorgung adressiert werden müssen.Dieser Beitrag beschreibt die Entwicklung des Konzeptes Psychosoziale Versorgung COVID-19 am LMU-Klinikum in München durch ein interdisziplinäres Team von Psychiater*innen, Psycholog*innen, Seelsorger*innen, Psychoonkolog*innen und Palliativmediziner*innen.Das neue Versorgungsmodell zur psychosozialen Unterstützung wurde für stationäre COVID-19-Patient*innen des Klinikums, deren Angehörige und Mitarbeiter*innen bestehend aus fünf Elementen implementiert.Das Angebot integriert innovative und nachhaltige Ansätze, wie den Einsatz telemedizinischer Interventionen, und unterstreicht den Wert interdisziplinärer Zusammenarbeit zur Bewältigung von Herausforderungen im Gesundheitswesen.

Herzlichen Gluckwunsch, Sie haben die erste Hurde genommen und sind zum Vortrag eingeladen! Sie gehoren zu den ca. acht Bewerbern, die fur den Vortrag eingeladen wurden.

Die Entscheidung der Berufungskommission hat fur unterschiedliche Personen eine unterschiedliche Bedeutung: entweder Ablehnung oder Listenplatz. Bei 30 Bewerbern gibt es 29 Ablehnungen. Deshalb wollen wir im Folgenden zunachst auf den Umgang mit einer Ablehnung eingehen.

Medical care provided at the hospital emergency rooms in Germany has hardly been explored. On the occasion of restructuring the Municipal Hospital, the Munich City Council initiated the "Round Table Emergency Care" in order to determine reference figures for capacity planning. The present study was designed to analyze treatment data from 14 emergency departments which mainly carry the city's hospital emergency service. For inpatient cases, data were used in accordance with §21 Hospital Charges Act, for outpatient cases - as far as available - similar data were used, anonymized and combined with data from prehospital emergency medical services (EMS). In order to describe the domains treatment urgency, diagnostic/therapeutic effort and bed requirements, data were categorized in a 4-stage system. Over 12 months, 524,716 treatment cases were recorded: 34% were admitted to hospital, 80% came without EMS. One in 7 patients who independently went to an emergency room needed a bed in the intensive care or intermediate care unit (ICU/IMC). There were 64 cases per day and per 100,000 inhabitants requiring 7 ICU/IMC and 15 regular ward beds. Most cases (66%) were treated as outpatients and presented to the hospital's emergency department at times when facilities of the ambulatory care system would have been available. Urgency of these cases was usually low (50.9%), but effort was often high, due to diagnostics and surgical procedures. This study offers fundamental knowledge for planning emergency care. A large proportion of the presentations, especially those with injuries and those with diagnosis that require a more differentiated work-up, seem to be medically justified, which is why appropriate capacities have to be planned in. The study also shows that capacity planning on the basis of EMS cases alone is an inappropriate, one-sided approach.Die Notfallversorgung in den deutschen Krankenhaus-Notaufnahmen ist kaum erforscht. Anlässlich der Restrukturierung des Städtischen Klinikums München initiierte der Stadtrat den „Runden Tisch Notfallversorgung“ um Richtzahlen für die Kapazitätsplanung zu erhalten. Die vorliegende Studie sollte dazu Behandlungsdaten von 14, an der Notfallversorgung hauptsächlich beteiligten, Krankenhausnotaufnahmen analysieren. Für stationäre Fälle wurden Daten nach §21 Krankenhausentgeltgesetz, für ambulante Fälle – soweit verfügbar – ähnliche Daten herangezogen, anonymisiert und mit Rettungsdienstdaten zusammengeführt. Um die Bereiche Behandlungsdringlichkeit, diagnostischer/therapeutischer Aufwand und Bettenbedarf beschreiben zu können wurden die Daten jeweils in einem vierstufigen System kategorisiert. Aus 12 Monaten wurden 524 716 Behandlungsfälle erfasst: 34% wurden stationär aufgenommen, 80% kamen ohne zu Hilfenahme des Rettungsdienstes. Jeder siebte Patient, der selbstständig eine Notaufnahme aufsuchte, benötigte ein Intensiv- oder Überwachungsbett (ICU/IMC). Pro Tag und 100 000 Einwohner stellten sich 64 Fälle mit einem Bettenbedarf von 7 ICU/IMC und 15 Normalstationsbetten vor. Die meisten Fälle (66%) wurden ambulant behandelt und kamen zu Zeiten, in denen kassenärztliche Notfallversorgungseinrichtungen erreichbar wären. Die Dringlichkeit dieser Fälle war meist gering (50,9%), der Aufwand oft aber hoch, begründet durch Diagnostik und chirurgische Versorgungen. Die Studie liefert Grundlagen zur Planung der Notfallversorgung. Ein Großteil der Vorstellungen scheint insbesondere bei Verletzungen und bei Krankheitsbildern, die einer differenzierten Abklärung bedürfen, medizinisch gerechtfertigt weshalb entsprechende Kapazitäten eingeplant werden müssen. Die Studie zeigt auch, dass eine Kapazitätsplanung allein auf der Basis der rettungsdienstlich vorgestellten Fälle eine ungeeignete, weil einseitige Betrachtungsweise ist.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Tumor-derived extracellular vesicles (EVs) induce pre-metastatic niche formation to promote metastasis. We isolated EVs from a highly-metastatic pancreatic cancer cell line and patient-derived primary cancer cells by ultracentrifugation. The protein content of EVs was analyzed by mass spectrometry. The effects of PDAC-derived EVs on natural kill (NK) cells were investigated by flow cytometry. The serum EVs&rsquo, TGF-&beta, 1 levels were quantified by ELISA. We found that integrins were enriched in PDAC-derived EVs. The expression of NKG2D, CD107a, TNF-&alpha, and INF-&gamma, in NK cells was significantly downregulated after co-culture with EVs. NK cells also exhibited decreased levels of CD71 and CD98, as well as impaired glucose uptake ability. In addition, NK cell cytotoxicity against pancreatic cancer stem cells was attenuated. Moreover, PDAC-derived EVs induced the phosphorylation of Smad2/3 in NK cells. Serum EVs&rsquo, 1 was significantly increased in PDAC patients. Our findings emphasize the immunosuppressive role of PDAC-derived EVs and provide new insights into our understanding of NK cell dysfunction regarding pre-metastatic niche formation in PDAC.

Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC). We evaluated the prognostic significance of this gene in PDAC patients. The expression of IFIT3 was analyzed in pancreatic cancer cell lines with different metastatic potential (FG and L3.6pl) and one established gemcitabine resistant cell variant-L3.6plGres. Second, we analyzed the protein expression in tissue microarrays (TMA) from specimens of 254 radically resected patients with pancreatic adenocarcinoma. The prognostic relevance of IFIT3 was evaluated by the Kaplan–Meier and Cox regression analysis. L3.6pl cells with an aggressive capacity showed a significant higher expression of IFIT3 as compared to FG cells. IFIT3 was accumulated in gemcitabine resistant cells. Overexpression of IFIT3 increased the resistance of apoptosis against gemcitabine treatment. Patients who had high expression of IFIT3 (32%) and received chemotherapy had a statistically significant reduced survival in multivariate analysis. High expression of IFIT3 enhances anti-apoptotic activity and chemotherapy resistance of PDAC cells. High expression of IFIT3 was independently correlated to shorter patients’ survival and may serve as a prognostic marker.

Mesenchymal stromal cells (MSCs) are adult progenitor cells with a high migratory and differentiation potential, which influence a broad range of biological functions in almost every tissue of the body. Among other mechanisms, MSCs do so by the secretion of molecular cues, differentiation toward more specialized cell types, or influence on the immune system. Expanding tumors also depend on the contribution of MSCs to building a supporting stroma, but the effects of MSCs appear to go beyond the mere supply of connective tissues. MSCs show targeted “homing” toward growing tumors, which is then followed by exerting direct and indirect effects on cancer cells. Several research groups have developed novel strategies that make use of the tumor tropism of MSCs by engineering them to express a transgene that enables an attack on cancer growth. This review aims to familiarize the reader with the current knowledge about MSC biology, the existing evidence for MSC contribution to tumor growth with its underlying mechanisms, and the strategies that have been developed using MSCs to deploy an anticancer therapy.

Peritoneal carcinomatosis (PC) is a cancer disease with an urgent need for effective treatment. Conventional chemotherapy failed to show acceptable results. Cytoreductive surgery and hyperthermic chemoperfusion (HIPEC) are only beneficial in few patients with resectable peritoneal metastasis. Immunotherapy could be attractive against PC, as all requirements for immunotherapy are available in the peritoneal cavity.This review analyzes the present literature for immunotherapy of PC. Advances from immune stimulators, radionucleotide-conjugated- and bispecific antibodies to future developments like adoptive engineered T-cells with chimeric receptors are discussed. The clinical development of catumaxomab, which was the first intraperitoneal immunotherapy to be approved for clinical treatment, is discussed. The requirements for future developments are illustrated. Expert commentary: Immunotherapy of peritoneal carcinomatosis is manageable, showing striking cancer cell killing. Improved profiles of adverse events by therapy-induced cytokine release, enhanced specific killing and optimal treatment schedules within multimodal treatment will be key factors.

A small subpopulation of cells within the bulk of tumors share features with somatic stem cells, in that, they are capable of self-renewal, they differentiate, and are highly resistant to conventional therapy. These cells have been referred to as cancer stem cells (CSCs). Recent reports support the central importance of a cancer stem cell-like niche that appears to help foster the generation and maintenance of CSCs. In response to signals provided by this microenvironment, CSCs express the tumorigenic characteristics that can drive tumor metastasis by the induction of epithelial-mesenchymal-transition (EMT) that in turn fosters the migration and recolonization of the cells as secondary tumors within metastatic niches. We summarize here recent advances in cancer stem cell research including the characterization of their genetic and epigenetic features, metabolic specialities, and crosstalk with aging-associated processes. Potential strategies for targeting CSCs, and their niche, by regulating CSCs plasticity, or therapeutic sensitivity is discussed. Finally, it is hoped that new strategies and related therapeutic approaches as outlined here may help prevent the formation of the metastatic niche, as well as counter tumor progression and metastatic growth.

BackgroundEarly allograft dysfunction after liver transplantation (LTX) is not well defined. The aim of this study was to evaluate the value of early post-transplant model for end-stage liver disease (MELD) scores for predicting long-term outcome after transplantation.MethodsIn this single-center retrospective study, 362 consecutive patients after LTX were included. MELD scores at 7, 14, and 21 postoperative days (PODs) were calculated from primary lab values. Receiver operating characteristic (ROC) analyses were carried out to determine the critical cutoff MELD scores for patient and graft survival.ResultsOne year after transplantation, the patient and graft survival rates were 85 and 69%, respectively. Although pretransplant MELD scores were similar, they were significantly different at POD7, POD14, and POD21 between patients who died and those who survived the first year after transplantation. As shown by ROC curves, for patient survival, the optimal time point is POD14 with a cutoff MELD of 17. At this time point, patients with a MELD below 17 showed a 1-year survival rate of 94.3% and patients with a MELD of 17 and higher showed a 1-year survival rate of only 75.4%. For graft survival, the optimal time point was day 7 and a cutoff MELD of 29 (92% at MELD

Background. The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). Methods. Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). ITand PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, s-Catenin, and Villin. Multivariate survival analysis was performed. Results. OS of PT patients was less compared with IT patients (25 vs 98 months; P

Pharmaceutical investigators are searching for preclinical models closely resembling the original cancer and predicting clinical outcome. This study compares drug response of three in vitro 3D-drug screening models with different complexity.Tumor cell line spheroids were generated from the cell lines Caco-2, DLD-1, COLO 205, HT-29 and HCT-116, and treated with clinically relevant combination therapies, namely 5-FU/oxaliplatin (FO), 5-FU/irinotecan (FI) and the molecular drugs Cetuximab, Trastuzumab, Vorinostat and Everolimus. Treatment results were compared with spheroids originated from tumor cell lines (Caco-2, DLD-1) co-cultured with stromal cells (PBMCs, cancer-associated fibroblasts of colorectal origin) and spheroids directly prepared from colon cancer tissues.Different microenvironment compositions altered the tumor cell line spheroid response patterns. Adding PBMCs increased resistance to FO treatment by 10–15% in Caco-2 and DLD-1 spheroids but decreased resistance to FI by 16% in DLD-1 spheroids. Fibroblast co-cultures decreased resistance to FI in Caco-2 spheroids by 38% but had no impact on FO. Treatment of colon cancer tissue spheroids revealed three distinct response pattern subgroups not detectable in 3D cell lines models.The cancer tissue spheroid model mimics both tumor characteristics and the stromal microenvironment and therefore is an invaluable screening model for pharmaceutical drug development.