Elucidation of the Mechanisms and Effects of Certain Anesthetic Interventions on Digestive Cancer Patients Subjected to Surgery

Contributions to the Elucidation of the Mechanisms and Effects by Which Certain Perianesthetic Interventions Modify Long-term Evolution of Patients With Digestive Cancers Subjected to Surgery

Digestive cancers (liver, colonic, pancreatic) have a high incidence and high mortality, their population prevalence is also increasing. Given that the anesthesia techniques and the agents used act directly and indirectly on the immune system during the perioperative period, influencing both the treatment and the prognosis of patients with colorectal cancer who undergo elective interventions, a series of perianesthetic interventions have been proposed in order to reduce morbidity-mortality perioperative.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: Blood extraction; Drug: Sevoflurane; Drug: Propofol; Drug: Lidocaine 1% Injectable Solution

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alexandru Alexa, MD; Phone Number: +40752691911; Email: alexandru_reziati@yahoo.com
• Study Contact Backup: Name: Ionescu Daniela, MD PHD; Phone Number: 0744771209; Email: dionescuati@yahoo.com

Study Locations

• Romania
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400469
      • Recruiting
      • Institutu Regional de Gastroenterologie si Hepatologi Prof. Dr. O. Fodor
      • Contact: Alexandru Alexa; Phone Number: +40752691911; Email: alexandru_reziati@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 80 years old patients admitted for elective colorectal surgery

Exclusion Criteria:

• Pre-existing chronic pain
• Chronic medication that may interfere with pain: antiepileptics, NSAIDs, corticosteroids
• Contraindications to any of the medications in the study
• Significant psychiatric disorders (Axis I disorder) (major depressive disorders, bipolar disorders, schizophrenia, etc.)
• Hepatic (ALT and / or AST> 2 normal wave) or renal (serum creatinine> 2 mg / dl)
• Convulsive conditions that require medication in the last 2 years
• Planned regional analgesia and / or anesthesia (spinal or epidural)
• Corticosteroid-dependent asthma
• Autoimmune disorders
• Antiarrhythmic drugs (verapamil, propafenone, amiodarone) that may interfere with the antiarrhythmic action of lidocaine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sevoflurane; Patients will receive a general volatile anesthesia with Sevoflurane as anesthetic agent	Biological: Blood extraction; The patients will donate after consent 10 ml of blood prior and after surgery for further study; Other Names: Biologic Human Blood; Drug: Sevoflurane; Patients will receive a general volatile anesthesia with Sevoflurane as anesthetic agent; Other Names: Volatile Anesthetic Drug
Experimental: Total intravenous anesthesia; Patients will receive a general anesthesia with Propofol as anesthetic agent	Biological: Blood extraction; The patients will donate after consent 10 ml of blood prior and after surgery for further study; Other Names: Biologic Human Blood; Drug: Propofol; Patients will receive a general anesthesia with Propofol as anesthetic agent; Other Names: Intravenous Anesthetic Drug
Experimental: Total intravenous anesthesia and Lidocaine; Patients will receive a general anesthesia with Propofol as anesthetic agent and will also receive a fully lidocaine infusion according to the lidocaine protocol	Biological: Blood extraction; The patients will donate after consent 10 ml of blood prior and after surgery for further study; Other Names: Biologic Human Blood; Drug: Lidocaine 1% Injectable Solution; Lidocaine 1% Injectable Solution Intervention Protocol for the TIVA and Lidocaine Arm; Induction: 1.5 mg / kg i.v. bolus before induction (at the vein catch).; Maintaining anesthesia: continuous infusion with Lidocaine 2 mg / kg / h, up to a maximum of 200 mg / h during maintenance (after IOT until waking); Infusion with 1% Lidocaine will be reduced to 1.0- 1.5 mg / kg / hour, max 100 mg / hour, for the first 48 hours postop; Other Names: Antiarrythmic drug
No Intervention: Placebo; 10 presumed healthy volunteers that have donated 10 ml of venous blood for serum comparison

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the antiproliferative and apoptotic effects of anesthetic agents	The investigators aim to correlate the anticancer effects of two anesthetic techniques with tumor markers (p53;p38) and cell proteins involved in proliferation or apoptosis (IGFR;Bcl-2;Bcl-6). The investigators will report if the anesthetic agent used in cancer surgery influences the serologic values of these markers.	up to 4 years
Evaluation of patients serum on cell culture	The investigators will investigate the serum of the patients who received different types of anesthesia (elective colorectal cancer surgery) by incubating it with colon cell lines (HCT116). The investigators will concentrate on cell proliferation assay. The investigators aim to discover how the growth of HCT116 will be influenced by patients' serum in terms of rate of proliferation. The measurements which will be used are Inhibitory Concentration (IC50) measured at 0 , 24 and 48 hours after incubation. The concentrations will be measured in mcg/ml.	up to 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lidocaine concentration	The investigators aim to determine de plasmatic concentration of lidocaine in the patients serum , which have received lidocaine perioperatively. The investigators will do a Mass-Spec analysis of lidocaine	up to 4 years
Survival Comparison	The investigators will do a follow up for the patients in all the 3 groups. The investigators want to investigate the survival ratio for the patients that had a elective colorectal cancer surgery.	up to 5 years

Collaborators and Investigators

• Sponsor: Iuliu Hatieganu University of Medicine and Pharmacy
• Collaborators: Institutul Regional de Gastroenterologie & Hepatologie Prof. dr. Octavian Fodor; Prof. Dr. I. Chiricuta Institute of Oncology
• Investigators: Study Director: Ionescu Daniela, MD PHD DEEA, UMF Iuliu Hatieganu Cluj-Napoca

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2018
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: October 13, 2019
• First Submitted That Met QC Criteria: November 10, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): February 10, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Propofol; Anesthesia; Lidocaine; Sevoflurane; Cell Culture
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics, General; Platelet Aggregation Inhibitors; Membrane Transport Modulators; Hypnotics and Sedatives; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Anesthetics, Inhalation; Anesthetics; Propofol; Lidocaine; Sevoflurane; Anesthetics, Intravenous
• Other Study ID Numbers: 418/14.11.2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No