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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Lidocaine 1% Injectable Solution
* Biological: Blood extraction
* Drug: Sevoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevoflurane<br>Patients will receive a general volatile anesthesia with Sevoflurane as anesthetic agent | Biological: Blood extraction<br>* The patients will donate after consent 10 ml of blood prior and after surgery for further study<br>* Other names: Biologic Human Blood;Drug: Sevoflurane<br>* Patients will receive a general volatile anesthesia with Sevoflurane as anesthetic agent<br>* Other names: Volatile Anesthetic Drug;|
| Experimental: Total intravenous anesthesia<br>Patients will receive a general anesthesia with Propofol as anesthetic agent | Biological: Blood extraction<br>* The patients will donate after consent 10 ml of blood prior and after surgery for further study<br>* Other names: Biologic Human Blood;Drug: Propofol<br>* Patients will receive a general anesthesia with Propofol as anesthetic agent<br>* Other names: Intravenous Anesthetic Drug;|
| Experimental: Total intravenous anesthesia and Lidocaine<br>Patients will receive a general anesthesia with Propofol as anesthetic agent and will also receive a fully lidocaine infusion according to the lidocaine protocol | Drug: Lidocaine 1% Injectable Solution<br>* 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<br>* Other names: Antiarrythmic drug;Biological: Blood extraction<br>* The patients will donate after consent 10 ml of blood prior and after surgery for further study<br>* Other names: Biologic Human Blood;|
| No Intervention: Placebo<br>10 presumed healthy volunteers that have donated 10 ml of venous blood for serum comparison | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, Propofol, Sevoflurane, Lidocaine, Cell Culture