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Perioperative immunomodulation with volatile anesthetics in cancer surgery

English title Perioperative immunomodulation with volatile anesthetics in cancer surgery
Applicant Beck Schimmer Beatrice
Number 150803
Funding scheme R'EQUIP
Research institution Institut für Anästhesiologie Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Immunology, Immunopathology
Start/End 01.01.2014 - 31.12.2014
Approved amount 112'818.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Surgery

Keywords (4)

Circulating Tumor Cells; Volatile Anesthetics; Immunomodulation; Cellsearch

Lay Summary (German)

Lead
Die Bedeutung von zirkulierende Tumorzellen bei Karzinompatienten bleibt weiterhin unklar. Dieses Forschungsprojekt zielt darauf hin ab, zirkulierende Tumorzellen in der Phase um die Tumorchirurgie herum zu bestimmen und die Rolle, die der Chirurgie und Anästhesie bei diesen Eingriffen zukommt, zu evaluieren.
Lay summary

Der Prozess der Metastasierung bei bösartigen Tumoren beinhaltet unter anderem das Loslösen von Tumorzellen, die über den Blut- oder Lymphweg zu Tumor-fernen Organen transportiert werden, wo sie als ‘Ableger’ wachsen. Im Rahmen der Tumorchirurgie ist es nicht unwahrscheinlich, dass durch die Entfernung des Karzinoms Tumorzellen freigesetzt werden und somit eine Metastasierung begünstigt würde. Bis anhin existieren keine zuverlässige Tumormarker, die eine detaillierte Aussage über die Prognose inklusive Metastasierung erlauben. Vor einigen Jahren wurde ein Gerät hergestellt, CellSearch® System genannt, mit dessen Hilfe zirkulierende Tumorzellen im Blut nachgewiesen werden können. Für einige Tumortypen wie Brust-, Prostata- und Dickdarmkrebs erlaubt diese Art von Diagnostik, erste vorsichtige Schlüsse bezüglich Prognose zu ziehen. Mit der Anschaffung dieses Gerätes wird uns ermöglicht, als erste Forschungsgruppe in der Schweiz Erfahrungen in der Detektion von zirkulierenden Tumorzellen im Blut zu sammeln. Gleichzeitig wird der Einfluss der Manipulation während tumorchirurgischen Eingriffen evaluiert, ebenso der Effekt von Anästhetika. Letztere üben eine immunmodulierende Wirkung aus, wobei nicht klar ist, ob volatile Anästhetika oder aber intravenös applizierte Anästhesiesubstanzen das Bestreben, von Seiten des Immunsystems die Tumorzellen zu eliminieren, unterstützen oder verhindern. Ziel dieses Forschungsgesuches soll sein, in zwei klinischen Studien zu evaluieren, welche Rolle der Chirurgie bezüglich Anzahl von zirkulierenden Tumorzellen in der Phase nach der Operation zukommt und ob es abhängig von der Art der durchgeführten Anästhesie Unterschiede gibt. Gleichzeitig soll die Anzahl von gemessenen zirkulierenden Tumorzellen mit dem klinischen Verlauf hinsichtlich Metastasierung korreliert werden.

 

Direct link to Lay Summary Last update: 16.12.2013

Responsible applicant and co-applicants

Publications

Publication
Anesthesia and colorectal cancer - The perioperative period as a window of opportunity?
Piegeler Tobias, Beck-Schimmer Beatrice (2016), Anesthesia and colorectal cancer - The perioperative period as a window of opportunity?, in European Journal of Surgical Oncology, 42, 1286-1295.
Detection of circulating tumor cells in patients with esophagogastric or pancreatic adenocarcinoma using the CellSearch® system: An observational feasibility study
Piegeler Tobias, Winder Thomas, Kern Sabine, Petalozzi Bernhard, Schneider Paul-Magnus, Beck-Schimmer Beatrice (2016), Detection of circulating tumor cells in patients with esophagogastric or pancreatic adenocarcinoma using the CellSearch® system: An observational feasibility study, in Oncology Letters, 12, 1513-1518.

Collaboration

Group / person Country
Types of collaboration
Wendelin Stark, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Paul Magnus Schneider, Department of Visceral and Transplantat Surgery, University Hospital Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Bernhard Pestalozzi, Department of Oncology, University Hospital Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Richard Minshall, Chicago United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Associated projects

Number Title Start Funding scheme
160283 Does anesthetic management have an impact on circulating tumor cells? 01.04.2015 Project funding (Div. I-III)
141216 Immunomodulatory Effects of Trifluorinated Small Molecules: New Therapeutic Opportunities for Ischemia-Reperfusion Injury 01.04.2012 Project funding (Div. I-III)
160283 Does anesthetic management have an impact on circulating tumor cells? 01.04.2015 Project funding (Div. I-III)

Abstract

Malignant tumors metastasize when cells detach from the primary tumor and reach the vascular com-partment, which transports them with the blood to distant sites such as lung, liver, brain or bone, where the cancer cells grow and manifest as a new tumor. Manipulation during cancer surgery is thereby a possible trigger favoring metastasis. Cancer patients undergoing a surgical or other treatment often expect reliable tests, which would allow prognosis with regard to recurrence as well as metastasis or even an overall estimation of the prognosis for the cancer disease. So far no biomarkers exist, which would allow an approximate estimation. Therefore the development or evaluation of new technologies aiming into this direction is of great interest. Years ago a cell search system was established detecting circulating tumor cells (CTC) in whole blood, which became approved in 2005 by the Food and Drug Administration (Cell-Search® System) for the use in metastatic breast cancer. Enumeration of CTC is based on magnetic separation of epithelial tumor cells using ferrofluid nanoparticles, which are coated with antibodies di-rected against epithelial antigens. With the help of cytokeratin and CD45 staining contaminating leukocytes are labeled and epithelial cells identified as such. Although various alternative methods are available to detect CTC, this technique is very promising.We aim to establish a platform for detection of CTC with the CellSearch® System at the University Hospital and the University of Zurich, but also for other institutions in Switzerland, where this equipment would be the first available in the country. Limited information is available with regard to CTC in perioperative phase after tumor surgery and the impact of these cells on recurrence-free survival. Also the influence of immunomodulatory agents such as anesthetics and opioids on tumor cell spread is not clear. Our group will specially focus on the possible immunomodulatory effect of anesthetics in the perioperative phase in cancer surgery. With a first trial patients with adenocarcinoma of the lower esophagus and the stomach undergoing complete tumor resection will be randomized for either a volatile or an intravenous anesthesia. Number of CTC during and after surgery will be determined and correlated to the outcome with a special focus on metastasis rate as well as disease-free and overall survival. A second clinical study will focus on CTC in breast cancer surgery, again determining these cells in the perioperative phase. Beside studies from our group collaboration with the Cancer Center of the University Hospital, the Department of Visceral- and Transplantation Surgery and Anesthesiology at the Balgrist University Hospital will be established. In conclusion, this new equipment would allow several groups to expand their research interest and possibly to monitor tumor growth and spread in general, with a special focus on the perioperative phase of the patient.
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