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Anesthesia and Immunological and Oxidative Stress in Relation to Abdominal Cancer Surgery (ANIMOX)

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ClinicalTrials.gov Identifier: NCT03974984
Recruitment Status : Not yet recruiting
First Posted : June 5, 2019
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Rune Børch Hasselager, University of Copenhagen

Brief Summary:

Colorectal cancer is a frequent type of cancer accounting for 600,000 deaths annually. Surgical resection remains the best treatment for long-term survival. However, studies suggest that events in the perioperative period can induce metastasis formation and tumor growth. Tumor cells are released into the blood stream during surgery and the surgical stress may create a favorable environment for dissemination of tumor cells into distant tissue. This is done by a cascade of pro-cancerous catecholamines, prostaglandins and cytokines combined with an impaired anti-cancerous cell mediated immune response.

Until recently, focus on the anesthetic management of cancer patients has been limited. Relatively small alterations in the perioperative anesthetic management may play a tremendous role in tumor progression. Optimizing anesthesia to reduce the surgical stress response could improve recurrence rates and long-term outcomes for cancer patients by inhibiting perioperative metastasis formation. Regional anesthesia and amide local anesthetics are suspected to calm the immunologic storm of prostaglandins, catecholamines and cytokines when used in the perioperative phase. Furthermore, volatile inhalational anesthesia is thought to modulate the immune system in a pro-cancerous way, while propofol may have opposite effects. Many of these recent studies are statistically underpowered and susceptible to bias, and experts in cancer treatment and anesthesia have emphasized the need for further research within this specific field.

In this study the investigators aim to characterize differences in the immunologic response to surgery between inhalational, total intravenous and epidural anesthesia. This will be done by analyzing blood samples obtained in the perioperative period in patients undergoing different modes of anesthesia. The Investigators will furthermore describe the quality of recovery for patients anesthetized with the different methods


Condition or disease Intervention/treatment
Anesthesia Colon Cancer Surgery Procedure: Colon Resection Procedure: Epidural anesthesia Drug: NSAID

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Detailed Description:

Background and Purpose Colorectal cancer is a frequent type of cancer accounting for 600,000 deaths annually. Surgical resection remains the best treatment for long-term survival. However, studies suggest that events in the perioperative period can induce metastasis formation and tumor growth. Tumor cells are released into the blood stream during surgery and the surgical stress may create a favorable environment for dissemination of tumor cells into distant tissue. This is done by a cascade of pro-cancerous catecholamines, prostaglandins and cytokines combined with an impaired anti-cancerous cell mediated immune response.

Until recently, focus on the anesthetic management of cancer patients has been limited. Relatively small alterations in the perioperative anesthetic management may play a tremendous role in tumor progression. Optimizing anesthesia to reduce the surgical stress response could improve recurrence rates and long-term outcomes for cancer patients by inhibiting perioperative metastasis formation. Regional anesthesia and amide local anesthetics are suspected to calm the immunologic storm of prostaglandins, catecholamines and cytokines when used in the perioperative phase. Furthermore, volatile inhalational anesthesia is thought to modulate the immune system in a pro-cancerous way, while propofol may have opposite effects. Many of these recent studies are statistically underpowered and susceptible to bias, and experts in cancer treatment and anesthesia have emphasized the need for further research within this specific field.

In this study the investigators aim to characterize differences in the immunologic response to surgery between patients anesthetized with TIVA, epidural and NSAID and patients anesthetized with total intravenous anesthesia alone. This will be done by analyzing blood samples obtained in the perioperative period in patients undergoing different modes of anesthesia. The Investigators will furthermore describe the quality of recovery for patients anesthetized with the different methods Objectives The investigators hypothesize that the immunologic response to surgery and metastasis progression are influenced by the anesthetic technique.

Methods The study is initiated by Center for Surgical Science, Department of Surgery, Zealand University Hospital.

The study will take place at Hvidovre Hospital. This is a Danish university hospital. It supports 500,000 people and is one of four main emergency hospitals in Copenhagen Denmark. About 300 laparoscopic colon resections are performed at this facility every year.

Intervention Participants will undergo laparoscopic colon resection for cancer. They will be anaesthetized according to the standard operating procedure at Hvidovre Hospital with the exception that no dexamethasone is administered as it could modulate the immune response. This includes anesthesia induction and maintenance with intravenous propofol and remifentanil. Patients will receive 4 mg ondansetron at the end of anesthesia.

A thoracic epidural catheter will be installed preoperatively and kept for up to three days. After an initial bolus with bupivacaine, continuous infusion of bupivacaine and sufentanil will be used to maintain the epidural analgesic effect. Postoperatively the epidural will be paused or discontinued if it is displaced or if side effects occur. It will only be re-installed if there is still need of neuraxial analgesia.

Patients will follow a standard Enhanced Recovery After Surgery (ERAS) protocol used at the facility.

Blood samples will be obtained before surgery and at four time points postoperatively and patient files will be assessed for adverse events within 30 days from surgery.

Withdrawal criteria:

Patients can be withdrawn from the study for any of the following reasons:

  • Failure to adhere to the anesthesia intervention described above- including failure to install effective continuous epidural anesthesia.
  • Adverse events after surgery Any complication over grade 2 in Clavien-Dindo (26) classification Blood transfusion Deep vein thrombosis or pulmonary embolism Anastomotic leak Acute renal failure Infection (wound infection or systemic infection) during the observation period.
  • After consultation patients can be withdrawn due to withdrawal of informed consent to participate in the study at the patients' own request at any time for any reason.

Population:

Study group: The "Hvidovre population":

The investigators will include patients undergoing laparoscopic hemicolectomy for cancer scheduled for anesthesia with total intravenous anesthesia combined with epidural anesthesia on Hvidovre Hospital according to the intervention described above.

Control group: The "Zealand University Hospital population" The immunological and oxidative stress in relation to abdominal surgery (IMOX) study is ongoing at Zealand University Hospital, Roskilde. It is a prospective explorative study cohort that consists of 60 patients undergoing laparoscopic colorectal cancer surgery. The aim of the study is to characterize the immunological and oxidative stress response to surgery. Outcomes similar to the primary and secondary outcomes of the ANIMOX-study are included in the IMOX-study. Patients are already included in the IMOX-study and blood samples are collected and kept in a bio bank.

The investigators will retrieve data on our main outcomes from the IMOX study in our analysis. Only electronic data will be used and no biologic material will be transferred from the IMOX project to ANIMOX. The population will be stratified according to anesthetic technique, which, according to the standard operating procedure, is either total intravenous anesthesia with propofol and remifentanil or volatile anesthesia with sevoflurane combined with a fast acting opioid (remifentanil or sufentanil). Patients anaesthetized with other techniques including epidural or other regional blocks will be excluded from the analysis.

Biological samples To characterize the immunological response to surgery the investigators obtain blood samples for analysis on postoperative day -1, 1, 2, 3 and 10 (or at the visit on day 10-14 where pathology results are given).

Handling of blood samples Blood samples will be drawn by a trained professional and analyzed immediately at the standard lab facilities at Hvidovre Hospital and destroyed immediately hereafter. The results will be accessible in Sundhedsplatformen.


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Study Type : Observational
Estimated Enrollment : 36 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Anesthesia and Immunological and Oxidative Stress in Relation to Abdominal Cancer Surgery
Estimated Study Start Date : July 4, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2020

Group/Cohort Intervention/treatment
The "Hvidovre population":
We will include patients undergoing laparoscopic hemicolectomy for cancer scheduled for anesthesia with total intravenous anesthesia combined with epidural anesthesia and perioperative NSAID on Hvidovre Hospital.
Procedure: Colon Resection
All patients undergo laparoscopic colon cancer resection.

Procedure: Epidural anesthesia
Epidural inserted preoperatively and kept for 1 day postoperatively

Drug: NSAID
NSAID administered according to standard operating procedure postoperatively

The "Zealand University Hospital population"

The immunological and oxidative stress in relation to abdominal surgery (IMOX) study is ongoing at Zealand University Hospital, Roskilde. It is a prospective explorative study cohort that consists of 60 patients undergoing laparoscopic colorectal cancer surgery.

The population has been anesthetized according to the standard operating procedure with either total intravenous anesthesia with propofol and remifentanil or volatile anesthesia with sevoflurane combined with a fast acting opioid (remifentanil or sufentanil). Patients anaesthetized with other techniques including epidural or other regional blocks will be excluded from the analysis.

Procedure: Colon Resection
All patients undergo laparoscopic colon cancer resection.




Primary Outcome Measures :
  1. Changes in neutrophil to lymphocyte ratio from preoperatively to day 1 postoperatively [ Time Frame: From preoperatively to day 1 postoperatively ]
    Changes in neutrophil to lymphocyte ratio from day 0 to day 1. The ratio will be estimated using absolute numbers from differential counts pre and postoperatively. A high neutrophil to lymfocyte ratio is related to poor outcome after cancer surgery


Secondary Outcome Measures :
  1. Changes in quality of recovery-15 score from preoperatively to day 1 postoperatively. [ Time Frame: Difference from preoperatively to day 1 postoperatively ]
    The QoR-15 questionnaire results in a score of 0-150 where a high score reflects good recovery.


Biospecimen Retention:   Samples Without DNA
Standard blood samples analyzed immediately after sampling. These include Hgb, Leucocytes including a differential count, thrombocytes, ALAT, LDH, Alkaline phosphatase, bilirubin, INR, albumin, Na, K, Creatinine, CRP and Glucose.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
We will include patients undergoing laparoscopic hemicolectomy for cancer scheduled for anesthesia with total intravenous anesthesia combined with epidural anesthesia on Hvidovre Hospital
Criteria

Inclusion Criteria:

  1. Patients over 18 years
  2. Patients diagnosed with colorectal cancer (UICC stadium I-III) and scheduled for laparoscopic hemicolectomy.
  3. ASA class I-III (Classification of the American Society of Anesthesiology)
  4. Patients scheduled for anesthesia with propofol, remifentanil and epidural anesthesia.
  5. Signed informed consent

Exclusion Criteria:

  1. Known immune-defects
  2. Patients undergoing neoadjuvant chemo or radiotherapy
  3. History of previous cancer
  4. Patients in immunomodulatory treatment within last 6 months
  5. Daily oral or intravenous steroid-use
  6. Patients that have undergone major surgery within one month before planned colon resection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03974984


Contacts
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Contact: Rune Hasselager, MD 31104653 ext 0045 rubh@regionsjaelland.dk
Contact: Ismail Gögenur, DMSc igo@regionsjaelland.dk

Locations
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Denmark
Hvidovre University hospital
Hvidovre, Capital Region, Denmark, 2650
Sponsors and Collaborators
University of Copenhagen
  Study Documents (Full-Text)

Documents provided by Rune Børch Hasselager, University of Copenhagen:

Publications:

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Responsible Party: Rune Børch Hasselager, Medical Doctor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT03974984     History of Changes
Other Study ID Numbers: SJ-704
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs