Publications by authors named "Karl-Walter Jauch"

240 Publications

Role of psychiatric hospitals during a pandemic: introducing the Munich Psychiatric COVID-19 Pandemic Contingency Plan.

BJPsych Open 2021 Feb 1;7(2):e41. Epub 2021 Feb 1.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany.

Background: Psychiatry is facing major challenges during the current coronavirus disease 2019 (COVID)-19 pandemic. These challenges involve its actual and perceived role within the medical system, in particular how psychiatric hospitals can maintain their core mission of attending to people with mental illness while at the same time providing relief to overstretched general medicine services. Although psychiatric disorders comprise the leading cause of the global burden of disease, mental healthcare has been deemphasised in the wake of the onslaught of the pandemic: to make room for emergency care, psychiatric wards have been downsized, clinics closed, psychiatric support systems discontinued and so on. To deal with this pressing issue, we developed a pandemic contingency plan with the aim to contain, decelerate and, preferably, avoid transmission of COVID-19 and to enable and maintain medical healthcare for patients with mental disorders.

Aims: To describe our plan as an example of how a psychiatric hospital can share in providing acute care in a healthcare system facing an acute and highly infectious pandemic like COVID-19 and at the same time provide support for people with mental illness, with or without a COVID-19 infection.

Method: This was a descriptive study.

Results: The plan was based on the German national pandemic strategy and several legal recommendations and was implemented step by step on the basis of the local COVID-19 situation. In addition, mid- and long-term plans were developed for coping with the aftermath of the pandemic.

Conclusions: The plan enabled the University Hospital to maintain medical healthcare for patients with mental disorders. It has offered the necessary flexibility to adapt its implementation to the first and second waves of the COVID-19 pandemic in Germany. The plan is designed to serve as an easily adaptable blueprint for psychiatric hospitals around the world.
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http://dx.doi.org/10.1192/bjo.2020.167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853741PMC
February 2021

[Psychosocial support during the COVID-19 pandemic: interdisciplinary concept of care at a university hospital].

Nervenarzt 2021 Jul 6;92(7):701-707. Epub 2020 Oct 6.

Klinik für Psychiatrie und Psychotherapie, LMU Klinikum, Nußbaumstraße 7, 80336, München, Deutschland.

Background: 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.

Objective And Method: 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.

Results: A new psychosocial first aid model has been implemented for COVID-19 inpatients, family members, and hospital staff consisting of five elements.

Conclusion: 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.
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http://dx.doi.org/10.1007/s00115-020-01014-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538057PMC
July 2021

Concurrent isolation of hepatic stem cells and hepatocytes from the human liver.

In Vitro Cell Dev Biol Anim 2020 Mar 27;56(3):253-260. Epub 2020 Mar 27.

Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, 5H 02 Room 428, Marchioninistr. 15, 81377, Munich, Germany.

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.
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http://dx.doi.org/10.1007/s11626-020-00433-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186250PMC
March 2020

Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers.

Semin Cancer Biol 2020 02 21;60:334-343. Epub 2019 Aug 21.

Department of General, Visceral und Tumor Surgery, University Hospital Cologne, Kerpener Straße 62, 50937, Cologne, Germany; Center for Integrated Oncology (CIO) Achen, Bonn, Cologne and Düsseldorf, Cologne, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.semcancer.2019.08.026DOI Listing
February 2020

[Analysis of Treatment Figures in the Munich Emergency Rooms 2013-2014].

Gesundheitswesen 2020 May 8;82(5):431-440. Epub 2019 Aug 8.

Institut für Notfallmedizin und Medizinmanagement (INM), Klinikum der Universität München (KUM), Ludwig-Maximilians-Universität (LMU), München.

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.
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http://dx.doi.org/10.1055/a-0925-8989DOI Listing
May 2020

Tumor-Derived Extracellular Vesicles Inhibit Natural Killer Cell Function in Pancreatic Cancer.

Cancers (Basel) 2019 Jun 22;11(6). Epub 2019 Jun 22.

Department of General, Visceral und Tumor Surgery, University Hospital Cologne, Kerpener Straße 62, 50937 Cologne, Germany.

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' TGF-β1 levels were quantified by ELISA. We found that integrins were enriched in PDAC-derived EVs. The expression of NKG2D, CD107a, TNF-α, and INF-γ 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' TGF-β1 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.
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http://dx.doi.org/10.3390/cancers11060874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628179PMC
June 2019

Targeting cancer stem cells and their niche: perspectives for future therapeutic targets and strategies.

Semin Cancer Biol 2018 12 3;53:139-155. Epub 2018 Aug 3.

General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.semcancer.2018.08.002DOI Listing
December 2018

Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma: The EORTC 62961-ESHO 95 Randomized Clinical Trial.

JAMA Oncol 2018 Apr;4(4):483-492

Department of Surgery, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.

Importance: Patients with soft tissue sarcoma are at risk for local recurrence and distant metastases despite optimal local treatment. Preoperative anthracycline plus ifosfamide chemotherapy improves outcome in common histological subtypes.

Objective: To analyze whether the previously reported improvement in local progression-free survival by adding regional hyperthermia to neoadjuvant chemotherapy translates into improved survival.

Design, Setting, And Participants: Open-label, phase 3 randomized clinical trial to evaluate the efficacy and toxic effects of neoadjuvant chemotherapy plus regional hyperthermia. Adult patients (age ≥18 years) with localized soft tissue sarcoma (tumor ≥5 cm, French Federation Nationale des Centers de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep) were accrued across 9 centers (6, Germany; 1, Norway; 1, Austria; 1, United States) from July 1997 to November 2006. Follow-up ended December 2014.

Interventions: After stratification for tumor presentation and site, patients were randomly assigned to either neoadjuvant chemotherapy consisting of doxorubicin, ifosfamide, and etoposide alone, or combined with regional hyperthermia.

Main Outcomes And Measures: The primary end point was local progression-free survival. Secondary end points included treatment safety and survival, with survival defined from date of randomization to death due to disease or treatment. Patients lost to follow-up were censored at the date of their last follow-up.

Results: A total of 341 patients were randomized, and 329 (median [range] age, 51 [18-70] years; 147 women, 182 men) were eligible for the intention-to-treat analysis. By December 2014, 220 patients (67%; 95% CI, 62%-72%) had experienced disease relapse, and 188 (57%; 95% CI, 52%-62%) had died. Median follow-up was 11.3 years. Compared with neoadjuvant chemotherapy alone, adding regional hyperthermia improved local progression-free survival (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86; P = .002). Patients randomized to chemotherapy plus hyperthermia had prolonged survival rates compared with those randomized to neoadjuvant chemotherapy alone (HR, 0.73; 95% CI, 0.54-0.98; P = .04) with 5-year survival of 62.7% (95% CI, 55.2%-70.1%) vs 51.3% (95% CI, 43.7%-59.0%), respectively, and 10-year survival of 52.6% (95% CI, 44.7%-60.6%) vs 42.7% (95% CI, 35.0%-50.4%).

Conclusions And Relevance: Among patients with localized high-risk soft tissue sarcoma the addition of regional hyperthermia to neoadjuvant chemotherapy resulted in increased survival, as well as local progression-free survival. For patients who are candidates for neoadjuvant treatment, adding regional hyperthermia may be warranted.

Trial Registration: clinicaltrials.gov Identifier: NCT00003052.
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http://dx.doi.org/10.1001/jamaoncol.2017.4996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885262PMC
April 2018

Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer.

Stem Cells Int 2017 6;2017:6012810. Epub 2017 Aug 6.

Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.

Cancer stem cells (CSCs) have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.
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http://dx.doi.org/10.1155/2017/6012810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563426PMC
August 2017

Allocation of Organs Should be Based on the Current Status of Medical Science.

Transplantation 2017 08;101(8):e283-e284

1 Walter-Brendel-Institute for Experimental Medicine, University of Munich Medical Center, Munich, Germany. 2 Faculty of Law, University of Munich, Munich, Germany. 3 University of Munich Medical Center, Munich, Germany.

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http://dx.doi.org/10.1097/TP.0000000000001800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542785PMC
August 2017

Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma.

J Cancer Res Clin Oncol 2017 Jun 17;143(6):1061-1068. Epub 2017 Feb 17.

Institute of Pathology, Ludwig-Maximilian-University (LMU), Thalkirchnerstr. 36, Munich, 80337, Germany.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1007/s00432-017-2351-4DOI Listing
June 2017

Genetic engineering of mesenchymal stromal cells for cancer therapy: turning partners in crime into Trojan horses.

Innov Surg Sci 2016 Sep 14;1(1):19-32. Epub 2016 Sep 14.

Department of General, Visceral, Transplantation and Vascular Surgery, Hospital of the University of Munich, Munich, Germany.

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.
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http://dx.doi.org/10.1515/iss-2016-0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753982PMC
September 2016

Prognosis of mucinous and signet-ring cell colorectal cancer in a population-based cohort.

J Cancer Res Clin Oncol 2016 Nov 29;142(11):2357-66. Epub 2016 Aug 29.

Tumorregister München (TRM) des Tumorzentrums München (TZM), Institut für medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Klinikum der Universität München (KUM), Marchioninistr. 15, 81377, Munich, Germany.

Purpose: Besides classical colorectal adenocarcinomas (AC), mucinous adenocarcinomas (MAC) and signet-ring cell carcinomas (SC) occur. Controversy remains regarding their prognostic role. Aim of this study was to define prognostic and histopathological specifications of mucinous and signet-ring cell colorectal cancer.

Methods: A total of 28,056 patients with AC, MAC, and SC between 1998 and 2012 in the catchment area of the Munich Cancer Registry were analyzed. Time to locoregional recurrence and distant recurrence was calculated by cumulative incidence. Survival was analyzed by the Kaplan-Meier method, calculation of relative survival, and Cox proportional hazards regression.

Results: AC occurred in 25,172 patients (90 %), MAC in 2724 (9.7 %), and SC in 160 (0.6 %). AC were less frequently localized in the proximal colon (34 %) compared to MAC (57 %, p < 0.001) and SC (76 %, p < 0.001). Both, MAC and SC had higher T, N, and M categories, lymphatic invasion, and worse grading (p < 0.001 for each). There were significant differences regarding the 10-year cumulative incidence of locoregional recurrence (p < 0.001), and distant recurrence (p < 0.001). For AC, the 5-year overall survival was 59 % (95 % confidence interval 58.0; 59.3), for MAC 52 % (50.2; 54.2), and for SC 40 % (32.1; 48.5; p < 0.001). However, MAC or SC did not remain independent prognostic factors for overall survival compared to AC upon multivariable analysis (p = 0.981).

Conclusion: This large cohort reveals specific histopathological and recurrence patterns for patients with colorectal AC, MAC, and SC. MAC and SC are diagnosed at more advanced tumor stages and therefore entail reduced survival rates.
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http://dx.doi.org/10.1007/s00432-016-2224-2DOI Listing
November 2016

The current status of immunotherapy in peritoneal carcinomatosis.

Expert Rev Anticancer Ther 2016 Oct 25;16(10):1019-27. Epub 2016 Aug 25.

b Medical Center of the Ludwig Maximilian University Munich , Munich , Germany.

Introduction: 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.

Areas Covered: 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.
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http://dx.doi.org/10.1080/14737140.2016.1224666DOI Listing
October 2016

Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex Vivo Tacrolimus Rinse Before Transplantation in EDC Livers.

Transplant Direct 2016 Jun 4;2(6):e76. Epub 2016 May 4.

Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the Ludwig-Maximilians-University, Munich, Germany.

Background: Organ shortage results in the transplantation of extended donor criteria (EDC) livers which is associated with increased ischemia-reperfusion injury (IRI). Experimental studies indicate that an organ rinse with the calcineurin inhibitor tacrolimus before implantation protects against IRI. The tacrolimus organ perfusion study was initiated to examine the effects of ex vivo tacrolimus perfusion on IRI in transplantation of EDC livers.

Methods: A prospective randomized multicenter trial comparing ex vivo perfusion of marginal liver grafts (≥2 EDC according to Eurotransplant manual) with tacrolimus (20 ng/mL) or histidine-tryptophane-ketoglutarate solution (control) was carried out at 5 German liver transplant centers (Munich Ludwig-Maximilians University, Berlin, Heidelberg, Mainz, Regensburg) between October 2011 and July 2013. Primary endpoint was the maximum alanine transaminase (ALT) level within 48 hours after transplantation. Secondary endpoints were aspartate transaminase (AST), prothrombine ratio, and graft-patient survival within an observation period of 1 week. After an interim analysis, the study was terminated by the scientific committee after the treatment of 24 patients (tacrolimus n = 11, Control n = 13).

Results: Tacrolimus rinse did not reduce postoperative ALT peaks compared with control (P = 0.207; tacrolimus: median, 812; range, 362-3403 vs control: median, 652; range, 147-2034). Moreover, ALT (P = 0.100), prothrombine ratio (P = 0.553), and bilirubin (P = 0.815) did not differ between the groups. AST was higher in patients treated with tacrolimus (P = 0.011). Survival was comparable in both groups (P > 0.05).

Conclusions: Contrary to experimental findings, tacrolimus rinse failed to improve the primary endpoint of the study (ALT). Because 1 secondary endpoint (AST) was even higher in the intervention group, the study was terminated prematurely. Thus, tacrolimus rinse cannot be recommended in transplantation of EDC livers.
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http://dx.doi.org/10.1097/TXD.0000000000000588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946517PMC
June 2016

Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells.

Int J Oncol 2016 Jul 10;49(1):99-110. Epub 2016 May 10.

Department of Surgery, Otto-von-Guericke University, Magdeburg, Germany.

Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multidrug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density.
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http://dx.doi.org/10.3892/ijo.2016.3512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902079PMC
July 2016

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

Transplantation 2016 Jan;100(1):116-25

1 Department of Surgery and Section of Experimental Surgery, University Hospital Regensburg, Regensburg, Germany. 2 Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. 3 Unite d'Hepatologie et de Transplantation Hepatique, Centre Hospitalier Universitaire Henri-Mondor, Service d'Hepatologie et de Gastroenterologie, Université Paris-Est Créteil Val-de-Marne, Paris, France. 4 Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche (DiSCOG), Università degli Studi di Padova, Padova, Italy. 5 Klinik für Allgemeine, Viszeral, Transplantations- Gefäß- und Thoraxchirurgie, Klinikum der Ludwig-Maximilians-Universität München-Großhadern, München, Germany. 6 Innere Medizin IV, Sektion Lebertransplantation, Universitätsklinikum Heidelberg, Heidelberg, Germany. 7 Klinik für Allgemein-, Viszeral- und Gefässchirurgie, Universitätsklinikum Jena, Jena, Germany. 8 Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany. 9 Centro Trapianti Fegato, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico IRCCS di Milano, Milan, Italy. 10 Chirurgia Epatobiliare e Trapianto Epatico, Azienda Ospedaliera di Padova, Università di Padova, Padova, Italy. 11 Alberta Health Services Liver Transplant Program, University of Alberta, Edmonton, Alberta, Canada. 12 Centre Hépato Biliaire, Hôpital Paul Brousse, Villejuif Cedex, Paris, France. 13 Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, Netherlands. 14 Service de Chirurgie Générale, Hépatique, Endocrinienne, et Transplantation, Hôpital de Hautepierre, Les Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 15 Service de Néphrologie-HTA-Dialyse-Transplantation, CHU Toulouse-Rangueil, Toulouse, France. 16 Department of Surgery and Transplantation, Sahlgrenska University Hospital, Göteborg, Sweden. 17 Hepatic-Pa

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 from sirolimus; 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.
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http://dx.doi.org/10.1097/TP.0000000000000965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683033PMC
January 2016

Model for end-stage liver disease score in the first 3 weeks after liver transplantation as a predictor for long-term outcome.

Eur J Gastroenterol Hepatol 2016 Feb;28(2):153-8

Departments of aGeneral, Visceral, Transplantation, Vascular and Thoracic Surgery bMedicine 2 cAnesthesiology, University of Munich, Munich, Germany dScientific Center of Surgery, Baku, Azerbaijan.

Background: Early 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.

Methods: In 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.

Results: One 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<29; 56.4% at MELD≥29). A multivariate analysis of potential risk factors indicated a significant role of serum bilirubin and MELD score determined on POD14 for patient survival.

Conclusion: In conclusion, early postoperative MELD scores predict outcome after LTX. The postoperative MELD score at POD14 is a good predictor for patient survival and at POD7 for the graft survival after LTX.
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http://dx.doi.org/10.1097/MEG.0000000000000505DOI Listing
February 2016

A-Part Gel, an adhesion prophylaxis for abdominal surgery: a randomized controlled phase I-II safety study [NCT00646412].

Ann Surg Innov Res 2015 2;9. Epub 2015 Sep 2.

Department of Surgery, University Munich-Großhadern, Marchioninistrasse 15, 81377 Munich, Germany.

Background: Intra-abdominal surgical intervention can cause the development of intra-peritoneal adhesions. To reduce this problem, different agents have been tested to minimize abdominal adhesions; however, the optimal adhesion prophylaxis has not been found so far. Therefore, the A-Part(®) Gel was developed as a barrier to diminish postsurgical adhesions; the aim of this randomized controlled study was a first evaluation of its safety and efficacy.

Methods: In this prospective, controlled, randomized, patient-blinded, monocenter phase I-II study, 62 patients received either the hydrogel A-Part-Gel(®) as an anti-adhesive barrier or were untreated after primary elective median laparotomy. Primary endpoint was the occurrence of peritonitis and/or wound healing impairment 28 ± 10 days postoperatively. As secondary endpoints anastomotic leakage until 28 days after surgery, adverse events and adhesions were assessed until 3 months postoperatively.

Results: A lower rate of wound healing impairment and/or peritonitis was observed in the A-Part Gel(®) group compared to the control group: (6.5 vs. 13.8 %). The difference between the two groups was -7.3%, 90 % confidence interval [-20.1, 5.4 %]. Both treatment groups showed similar frequency of anastomotic leakage but incidence of adverse events and serious adverse events were slightly lower in the A-Part Gel(®) group compared to the control. Adhesion rates were comparable in both groups.

Conclusion: A-Part Gel(®) is safe as an adhesion prophylaxis after abdominal wall surgery but no reduction of postoperative peritoneal adhesion could be found in comparison to the control group. This may at least in part be due to the small sample size as well as to the incomplete coverage of the incision due to the used application.

Trial Registration: NCT00646412.
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http://dx.doi.org/10.1186/s13022-015-0014-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557926PMC
September 2015

Thirty-day mortality leads to underestimation of postoperative death after liver resection: A novel method to define the acute postoperative period.

Surgery 2015 Dec 19;158(6):1530-7. Epub 2015 Aug 19.

Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Munich, Germany. Electronic address:

Background: Postoperative mortality commonly is defined as death occurring within 30 days of surgery or during hospitalization. After resection for liver malignancies, this definition may result in underreporting, because mortality caused by postoperative complications can be delayed as the result of improved critical care. The aim of this study was to estimate statistically the acute postoperative period (APP) after partial hepatectomy and to compare mortality within this phase to standard timestamps.

Methods: From a prospective database, 784 patients undergoing resection for primary and secondary hepatic malignancies between 2003 and 2013 were reviewed. For estimation of APP, a novel statistical method applying tests for a constant postoperative hazard was implemented. Multivariable mortality analysis was performed.

Results: The APP was determined to last for 80 postoperative days (95% confidence interval 40-100 days). Within this period, 55 patients died (7.0%; 80-day mortality). In comparison, 30-day mortality (N = 32, 4.0%) and in-hospital death (N = 39, 5.0%) were relevantly less. No patient died between postoperative days 80 and 90. The causes of mortality within 30 days and from days 30-80 did not greatly differ, especially regarding posthepatectomy liver failure (44% vs 39%, P = .787). Septic complications, however, tended to cause late deaths more frequently (43% vs 25%, P = .255). Comorbidities (Charlson comorbidity index ≥ 3; P = .046), increased preoperative alanine aminotransferase activity (P = .030), and major liver resection (P = .035) were independent risk factors of 80-day mortality.

Conclusion: After liver resection for primary and secondary malignancies, 90-day rather than 30-day or in-hospital mortality should be used to avoid underreporting of deaths.
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http://dx.doi.org/10.1016/j.surg.2015.07.019DOI Listing
December 2015

Outcome of gastric cancer in the elderly: a population-based evaluation of the Munich Cancer Registry.

Gastric Cancer 2016 Jul 11;19(3):713-22. Epub 2015 Aug 11.

Munich Cancer Registry (MCR), Munich Tumour Centre (TZM), Department of Medical Informatics, Biometry and Epidemiology (IBE), Klinikum Großhadern, Ludwig-Maximilians-University (LMU), Marchioninistr. 15, 81377, Munich, Germany.

Background: Gastric cancer accounts for 5 % of cancer deaths. Proportions of older stomach cancer patients are increasing. Despite the still poor prognosis, standardised treatment has achieved improvements; nonetheless it is questionable whether all age groups have benefitted. Age and outcome need to be examined in a population-based setting.

Methods: Analyses included Munich Cancer Registry (MCR) data from 8601 invasive gastric cancer patients, diagnosed between 1998 and 2012. Tumour and therapy characteristics and outcome were analysed by two age groups (<70 vs. ≥70 years). Survival was analysed using the Kaplan-Meier method and relative survival was computed as an estimation for cancer-specific survival. Additional landmark analyses were conducted by calculating conditional survival of patients who survived more than 6 months.

Results: Fifty-nine per cent of the cohort were ≥70 years old. These patients had tumours with a slightly better prognosis and were treated with less radical surgery and adjuvant therapy than younger patients. The 5-year relative survival was 40 % for the youngest (<50 years) and 23 % for the oldest patients (≥80 years). Survival differences were diminished or eliminated after landmark analyses: The 5-year relative survival in age groups 50-59, 60-69 and 70-79 years was comparable (between 48 and 49.6 %) and slightly worse in the youngest and oldest (45 %), which may be explained by more aggressive tumours and effects of cellular senescence, respectively.

Conclusion: The treatment and care of elderly gastric cancer patients in the MCR catchment area seems appropriate: if a patient's general condition allows oncologic resection and chemotherapy, it is conducted and the result is comparable between age groups.
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http://dx.doi.org/10.1007/s10120-015-0527-7DOI Listing
July 2016

Histomorphologic and molecular phenotypes predict gemcitabine response and overall survival in adenocarcinoma of the ampulla of Vater.

Surgery 2015 Jul 26;158(1):151-61. Epub 2015 Mar 26.

Department of General-, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University of Munich, Munich, Germany; Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany. Electronic address:

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). IT and PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, ß-Catenin, and Villin. Multivariate survival analysis was performed.

Results: OS of PT patients was less compared with IT patients (25 vs 98 months; P < .001), whereas it was comparable with patients with PDAC (25 vs 14 months; P = .123). PT patients receiving adjuvant gemcitabine chemotherapy featured improved OS (32 vs 13 months; P = .013), whereas gemcitabine tended to be associated with decreased OS in IT patients (35 vs 112 months; P = .193). Besides histopathologic classification, expression of CK7 and MUC2 were important prognostic variables. PT patients with CK7-positivity or MUC2-negativity were segregated into an even poorer prognostic group.

Conclusion: PapCa is not a separate tumor entity. We demonstrate important differences between IT-PapCa and PT-PapCa not only in long-term survival but also in response to adjuvant gemcitabine. Tumor biology and clinical course of PT tumors resemble those of PDAC. PT tumors should therefore be treated like PDAC.
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http://dx.doi.org/10.1016/j.surg.2015.02.001DOI Listing
July 2015

Impact of the spheroid model complexity on drug response.

J Biotechnol 2015 Jul 3;205:14-23. Epub 2015 Mar 3.

SpheroTec GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany; Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University of Munich, Campus Großhadern, Marchioninistr. 15, 81377 Munich, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jbiotec.2015.02.029DOI Listing
July 2015

Overexpression of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in pancreatic cancer: cellular "pseudoinflammation" contributing to an aggressive phenotype.

Oncotarget 2015 Feb;6(5):3306-18

Department of Surgery, Medical Center of the Otto-von-Guericke-University, Magdeburg, Germany.

Inflammation contributes to important traits that cancer cells acquire during malignant progression. Gene array data recently identified upregulation of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in aggressive pancreatic cancer cells. IFIT3 belongs to the group of interferon stimulated genes (ISG), can be induced by several cellular stress stimuli and by its tetratricopeptide repeats interacts with a multitude of cellular proteins. Upregulation of IFIT3 was confirmed in the aggressive pancreatic cancer cell line L3.6pl compared with its less aggressive cell line of origin, COLO357FG. Transgenic induction of IFIT3 expression in COLO357FG resulted in greater mass of orthotopic tumors and higher prevalence of metastases. Several important traits that mediate malignancy were altered by IFIT3: increased VEGF and IL-6 secretion, chemoresistance and decreased starvation-induced apoptosis. IFIT3 showed binding to JNK and STAT1, the latter being an important inducer of IFIT3 expression. Despite still being alterable by "classical" IFN or NFκB signaling, our findings indicate constitutive - possibly auto-regulated - upregulation of IFIT3 in L3.6pl without presence of an adequate inflammatory stimulus. The transcription factor SOX9, which is linked to regulation of hypoxia-related genes, was identified as a key mediator of upregulation of the oncogene IFIT3 and thereby sustaining a "pseudoinflammatory" cellular condition.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413655PMC
http://dx.doi.org/10.18632/oncotarget.2494DOI Listing
February 2015

Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer.

Target Oncol 2015 Dec 3;10(4):535-48. Epub 2015 Feb 3.

Department of General, Visceral und Vascular Surgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120, Magdeburg, Germany.

Our preliminary studies identified a small population side population (SP) cells in pancreatic cancer cells with stem cell-like properties, which were able to induce fast and aggressive tumor formation in nude mice. Gene expression analysis showed a significant difference in the expression of more than 1,300 genes in SP cells, among which a highly significant difference in microRNA expression of miR-21 and miR-221 between SP and NSP cells was identified. SP cells were identified and characterized by flow cytometry using Hoechst 33342 dye staining from a highly metastatic human pancreatic cancer cell line (L3.6pl). Antagomir transfection was performed using miRNA-21 and miRNA-221 antisense oligonucleotides (ASOs) and followed by detection of cell apoptosis, cell cycle progression, chemosensitivity, and invasion. Sorted SP cells from gemcitabine-resistant L3.6pl cells (L3.6pl(Gres)-SP) cells were orthotopically implanted in nude mice with or without miRNA-21 and miRNA-221 ASOs mono- and combination therapy. The administration of antagomir-21 and antagomir-221 significantly reduced the SP cell fraction, decreased SP cell differentiation, and downstream gene regulation, and thereby induced reduction of L3.6pl cell proliferation, invasion, and chemoresistance against gemcitabine and 5-Fluorouracil. Combination of ASOs therapy against miRNA-21 and miRNA-221 significantly inhibited primary tumor growth and metastasis compared to single antagomir treatment, especially, in L3.6plGres-SP-induced pancreatic tumor growth in vivo. These findings further indicate that the inhibition of miR-21 and miR-221 appear particularly suitable to target stem-like subpopulations and address their specific biological function to promote tumor progression in pancreatic cancer.
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http://dx.doi.org/10.1007/s11523-015-0360-2DOI Listing
December 2015

Impact of perioperative allogeneic red blood cell transfusion on recurrence and overall survival after resection of colorectal liver metastases.

Dis Colon Rectum 2015 Jan;58(1):74-82

Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, University of Munich, Campus Grosshadern, Munich, Germany.

Background: Perioperative allogeneic red blood cell transfusion has been conclusively shown to be associated with adverse oncologic outcomes after resection of nonmetastatic colorectal adenocarcinoma.

Objective: The aim of the study was to identify risk factors for a perioperative transfusion and to assess the effects of transfusion on survival after curative-intended resection of hepatic metastases in patients featuring stage IV colorectal cancer.

Design: This was an observational study with a retrospective analysis of a prospective data collection.

Setting: The study was conducted at a tertiary care center.

Patients: A total of 292 patients undergoing curative-intended liver resection for colorectal liver metastases were included in the study.

Main Outcome Measures: Univariate and multivariate analyses were performed identifying factors influencing transfusion, recurrence-free survival, and overall survival.

Results: A total of 106 patients (36%) received allogeneic red blood cells. Female sex (p = 0.00004), preoperative anemia (p = 0.001), major intraoperative blood loss (p < 0.00001), and major postoperative complications (p = 0.02) were independently associated with the necessity of transfusion. Median recurrence-free and overall survival were 58 months. Allogeneic red blood cell transfusion was significantly associated with reduced recurrence-free survival (32 vs 72 months; p = 0.008). It was reduced further by administration of >2 units (27 months; p = 0.02). Overall survival was not significantly influenced by transfusion (48 vs 63 months; p = 0.08). When multivariately adjusted for major intraoperative blood loss and factors univariately associated, namely comorbidities, tumor load, and positive resection margins, transfusion was an independent predictor for reduced recurrence-free survival (p = 0.03).

Limitations: These include the retrospective and observational design, as well as the impossibility to prove causality of the association between transfusion and poor outcome.

Conclusions: In patients undergoing liver resection for colorectal liver metastases, perioperative transfusion is independently associated with earlier disease recurrence. This emphasizes appropriate blood management measures, including the conservative correction of preoperative anemia, the use of low transfusion triggers, and the minimization of intraoperative blood loss.
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http://dx.doi.org/10.1097/DCR.0000000000000233DOI Listing
January 2015

Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study.

Ann Surg 2014 Nov;260(5):749-54; discussion 754-6

*Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery and †Department of Internal Medicine III, University of Munich-Campus Grosshadern, Munich, Germany ‡Sarcoma Unit ITM-Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany §Institute of Medical Informatics, Biometry, and Epidemiology, University of Munich-Campus Großhadern, Munich, Germany ¶Department of General, Visceral, and Vascular Surgery, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany.

Objective: To determine whether regional hyperthermia (RHT) in addition to chemotherapy improves local tumor control after macroscopically complete resection of abdominal or retroperitoneal high-risk sarcomas.

Background: Within the prospectively randomized EORTC 62961 phase-III trial, RHT and systemic chemotherapy significantly improved local progression-free survival (LPFS) and disease-free survival (DFS) in patients with abdominal and extremity sarcomas. That trial included macroscopically complete and R2 resections.

Methods: A subgroup analysis of the EORTC trial was performed and long-term survival determined. From 341 patients, 149 (median age 52 years, 18-69) were identified with macroscopic complete resection (R0, R1) of abdominal and retroperitoneal soft-tissue sarcomas (median diameter 10 cm, G2 48.3%, G3 51.7%). Seventy-six patients were treated with EIA (etoposide, ifosfamide, doxorubicin)+RHT (≥5 cycles: 69.7%) versus 73 patients receiving EIA alone (≥5 cycles: 52.1%, P=0.027). LPFS and DFS as well as overall survival were determined.

Results: RHT and systemic chemotherapy significantly improved LPFS (56% vs 45% after 5 years, P=0.044) and DFS (34% vs 27% after 5 years, P=0.040). Overall survival was not significantly improved in the RHT group (57% vs 55% after 5 years, P=0.82). Perioperative morbidity and mortality were not significantly different between groups.

Conclusions: In patients with macroscopically complete tumor resection, RHT in addition to chemotherapy resulted in significantly improved local tumor control and DFS without increasing surgical complications. Within a multimodal therapeutic concept for abdominal and retroperitoneal high-risk sarcomas, RHT is a treatment option beside radical surgery and should be further evaluated in future trials.
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http://dx.doi.org/10.1097/SLA.0000000000000978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514521PMC
November 2014

Has the minimum caseload requirement failed? Strategic planning in the hospital sector requires input from elected political representatives.

Dtsch Arztebl Int 2014 Aug;111(33-34):547-8

Surgical Clinic and Policlinic, Großhadern Hospital, Ludwig- Maximilian-Universität, Munich.

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http://dx.doi.org/10.3238/arztebl.2014.0547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165181PMC
August 2014
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