Neoplasms

Digestive System Diseases

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Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Colorectal Neoplasms

Respiratory Aspiration

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

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Intestinal Diseases

Rectal Diseases

Central Nervous System Depressants

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Anesthetics

Propofol

Isoflurane

Remifentanil

Benzocaine

Tannic Acid

* include 35 patients with colorectal cancer undergoing surgery
* anaesthesia is induced and maintained with total intravenous target-controlled infusion ( TIVA-TCI) of propofol and remifentanil.
* for propofol initial target plasma concentration (Cp) is set to 4 micrograms/ml (modified Marsh model)( Base Primea™, Fresenius, France) and then adjusted in steps 0.2 micrograms/ml to maintain the BIS values between 40-55 during surgery.
* for Remifentanil initial Cp is set at induction at 4 ng/ml and then the Cp is maintained between 3-8 ng/mL(increments of 0.5 ng/ml in case of inadequate anesthesia).
* intervention:blood sampling for IL measurement

* include 35 patients with colorectal cancer undergoing surgery
* anesthesia is induced with propofol bolus 1,5-2 mg/kg and remifentanil TCI mode (Minto model) (Base Primea™, Fresenius, France) with an initial Cp 4 ng/ml
* maintenance of anesthesia is achieved with isoflurane 1-1.5 MAC in order to maintain the BIS value between the values of 40-55 and remifentanil TCI with Cp between 3-8 ng/mL (increments of 0.5 ng/ml in case of inadequate anesthesia)
* intervention:blood sampling for IL measurement

Blood sampling to determine interleukins IL6 , IL10 plasma levels are drawn at the following moments:

* T0- before the induction of anesthesia (venous cannula insertion time)
* T1- after induction but before starting surgery

  * In the group I (TIVA -TCI) when the plasma concentration of propofol is 3-3.5 ng/ml
  * In group II (ISOFLURANE) when concentration of isoflurane in exhaled air (Et Isoflurane) is between 0.3-0.5%
* T2, T3- at 2 and 24 hours after surgery

blood sampling for IL measurement

Simona C Margarit, lecturer

Knowing the fact that the anesthetic substances can alter the immune response during the surgery, the purpose of the study is to evaluate the influence of two general anesthetic techniques - inhalation vs. total intravenous anesthesia on the immune response in patient with colorectal surgery for neoplastic disease, evaluated by the plasma level of the interleukins 6 and 10(IL6, IL10).

Introduction

Several factors are contributing to perioperative immunosuppression such as: surgery itself, general anesthesia. In vivo and in vitro studies have shown that anesthesia itself may alter the immune response either by direct effect on immune cells (such as natural killer and T helper) ) or indirectly by the influence of anesthetic substances on pro (IL-1, IL-6, tumor necrosis factor alpha ) and anti-inflammatory ( IL-4, IL-10) cytokines release.

The study aims to evaluate the influence of two general anesthetic techniques inhalation versus total intravenous anesthesia- target controlled infusion (TIVA-TCI) on the immune response in patient with colorectal surgery for neoplastic disease, evaluated by the plasma level of the interleukins IL6, IL10.

Study group:

- patients admitted to the Surgical Clinic of the Regional Institute of Gastroenterology and Hepatology Prof Dr Octavian Fodor, undergoing open surgery for colorectal cancer (right/left colectomy, colorectal resection).

After obtaining written informed consent 70 ASA physical status I-III patients scheduled for colorectal cancer resection are randomly allocated to 2 groups of study by computer randomization:

* group I, TIVA-TCI (n=35 patient) receive total intravenous-target controlled infusion anesthesia with propofol and remifentanil
* group II (ISOFLURANE) (n=35 patients) receive inhalatory anesthesia with isoflurane and remifentanil

Methods:

* Premedication with midazolam 7.5 mg orally 30 min before surgery in all patients.
* On arrival in the operating room a venous cannula is inserted and a blood sample for interleukin measurement is performed. This cannula is designated for fluid administration during anesthesia and for blood sampling for subsequent interleukin measurements. A second cannula is inserted for the administration of anesthetic substances.

In group I (TIVA-TCI):

* anesthesia is induced with a target-controlled infusion (TCI) of propofol with an initial target plasma concentration (Cp) of 4 micrograms/ml (modified Marsh model)( Base Primea™, Fresenius, France), adjusted in steps 0.2 micrograms/ml to maintain the BIS values between 40-55 during surgery.
* propofol infusion stops at the end of surgery before the last 2 stitches.

In group II (ISOFLURANE):

* anesthesia is induced with propofol bolus 1,5-2 mg/kg.
* maintenance of anesthesia is achieved with isoflurane 1-1.5 MAC in order to maintain the BIS value between the values of 40-55.
* isoflurane administration cease before the last 2 stitches.

In both groups:

* remifentanil TCI mode (Minto model) (Base Primea™, Fresenius, France) is used for analgesia, with an initial Cp of remifentanil set at 4 ng/ml at induction, and a Cp between 3-8 ng/mL during maintenance(increments of 0.5 ng/ml) depending on the painful moments of surgery and the patient's analgesic needs assessed by changes in heart rate, blood pressure (more than 20% of the previous value of induction), sweating, tearing.
* remifentanil infusion ceases after suturing the wound.
* muscle relaxation is achieved with atracurium, 0.5-0.6 mg/kg at induction, and further maintained on top up doses as needed. At the end of surgery the residual neuromuscular blockade is reversed with atropine 0.02mg/kg and neostigmine 0.0 5mg/kg.
* the lungs are ventilated with an air/oxygen mixture.

Postoperative analgesia:

* morphine patient controlled analgesia(PCA ) with boluses of 1 mg to 5 min interval to maintain the VAS ˂ 4 on 10-point visual analogue scale (VAS). The first dose of morphine 0.1 mg/kg is administered 40 minutes before completing the surgery.
* in addition to morphine, is given paracetamol intravenous, 1g every 8 hours. The first dose of paracetamol is administered intra-operatively before the end of surgery.

Monitoring:

1. Intraoperative:

   * ASA basic monitoring: continuous monitoring ECG, heart rate (HR), arterial blood pressure (BP), pulse oximetry (SpO2), CO2 concentration in expired gases (Et CO2), concentration of isoflurane in exhaled gases (Et Iso), minimum alveolar concentration (MAC) of isoflurane, and core temperature.
   * depth of anesthesia - bispectral index (BIS) (BIS Vista -Aspect Medical System, USA).

   Systolic, diastolic blood pressure and HR are recorded every minute at induction time and every 5 minutes after endotracheal intubation, until the end of surgery.

   Hypotension (defined as a decrease of mean arterial blood pressure by over 20% of baseline values) is treated with higher rate of infusion solutions and intravenous boluses of ephedrine 5 mg.

   Inadequate anesthesia (hypertension, tachycardia, lacrimation, sweating) is treated by adjusting the remifentanil infusion as previously mentioned.
2. Postoperative:

   * opioid analgesic requirement in the first 24 hours
   * pain score on the visual analog scale (VAS 0-10)in the first 24 hour
   * incidence of postoperative nausea and vomiting episodes requiring the administration of antiemetic drug (metoclopramide 20 mg or ondansetron 4 mg)

Blood sampling to determine interleukins IL6 , IL10 plasma levels are drawn at the following moments:

* T0- before the induction of anesthesia (venous cannula insertion time)
* T1- after induction but before starting surgery:

  * in group I (TIVA -TCI) when the plasma concentration of propofol is 3-3.5 micrograms/ml
  * in group II (ISOFLURANE) when concentration of isoflurane in exhaled air (Et Isoflurane) is between 0.3-0.5%
* T2, T3 - at 2 and 24 hours after surgery

The collected blood samples are centrifuged at 2500 rpm / min for 10 minutes and the resulting plasma is stored at -70 ° C until the interleukins assay is performed.

If intraoperatively is revealed local extension of colorectal cancer (tumor invades adjacent organs) or distant metastasis the patient is excluded from the study.

Data collection is done longitudinally prospective, for each patient the following variable are registered:

* quantitative: - weight, plasmatic or brain concentration of the anesthetics used in TIVA-TCI mode, BIS value, plasmatic concentration of the interleukins on 4 intra- and post-operatory moments, the duration of the surgery and anesthesia, number of episodes of nausea and vomiting, opioid analgesic requirement.
* qualitative: ASA score, sex, post-operatory pain score (VAS) Collected data are introduced in a database using the Excel Office programme.

The statistical analysis will be performed using the SPSS 16.0 software (SPSS Inc Chicago, IL, USA). Quantitative variables will be expressed as mean ± SD, and qualitative variables as absolute and relative frequencies. Given multiple measurements at different time intervals, area under curve (AUC) is calculated for each IL and the results will be compared between groups.A p less 0.05 will be considered significant.

The collected blood samples are centrifuged at 2500 rpm / min for 10 minutes and the resulting plasma is stored at -70 °

Anesthetic Technique on Immune Response in Colorectal Cancer

The Influence of Anesthetic Technique on Interleukin Plasma Level in Colorectal Cancer Surgery - TIVA vs Inhalation Anesthesia

at 15, 30 minutes post surgery 6, 12, 18, 24 hours postoperatively

total dose (mg) of remifentanil administered in TCI mode during surgery

-once the intravenous cannula is inserted

* in group I (TIVA-TCI) when plasma concentration of propofol is 3-3.5 micrograms/ml
* in group II (ISOFLURANE) when concentration of isoflurane in exhaled gases (Et iso) is between 0.3-0.5 %

Iuliu Hatieganu University of Medicine and Pharmacy

senior lecturer, consultant in anesthesia and intensive care

Neoplasm Metastasis

Platelet Aggregation Inhibitors

Sevoflurane

Anesthetics, General

Hypnotics and Sedatives

Anesthetics, Intravenous

Anesthetics, Inhalation

Analgesics, Opioid

Narcotics

The anesthesia of patients in the total intravenous anesthesia group will be maintained with propofol and remifentanil.

The anesthesia of patients in the inhalational anesthesia group will be maintained with sevoflurane and remifentanil.

Propofol will be used for anesthesia maintenance in the total intravenous anesthesia group.

Sevoflurane will be used for anesthesia maintenance in the inhalation anesthesia group.

Remifentanil will be used for analgesia in both groups.

Guizhi Du, MD, PhD

Jin Liu, MD, PhD

Yan Qiu, MD

The body immunity is important to the development of tumor. The immune system is in charge of monitoring and cleaning tumor cells in circulation. Anesthesia may alter the immune response and affect the elimination of tumor cells. The purpose of the trial is to test whether inhalational anesthetic is relevant to tumor metastasis and recurrence of patients undergoing colorectal cancer resection through depression of lymphocytes-mediated immunity.

With the increasing number of patients diagnosed with colorectal cancer, the proportion of patients undergoing surgical resection with general anesthesia increased. However, the operation can lead tumor cells releasing into the blood or peritoneal implantation, and the impaired immune response can make patients susceptible to the development of tumor metastasis and recurrence which is the the main reason of death. It is well known that B lymphocytes and T lymphocytes are the main immune cells, and B lymphocytes by secreting antibodies are related to humoral immunity and T lymphocytes which play the most important role in antitumor are related to cell-mediated immunity. Surgery stress leads to metabolic and neuroendocrine changes causing significant depression of immunity. Although general anesthesia could reduce surgical stress, studies indicated general anesthetics including intravenous and inhalational agents both have variable effects on tumor cells growth by immuno-modulation and some cytokines. A number of studies have demonstrated deleterious effects on the function of lymphocytes associated with the administration of volatile inhalational anesthetic agents. It was suggested that the use of volatile inhalational agent may augment tumor cells growth by inhibiting the activity of lymphocytes, NK cells and dendritic cells which are important for recognizing, capturing and killing tumor cells, however, the alternative propofol has a converse (beneficial) effect by decreasing the plasma level of cytokines secreted by activated lymphocytes, macrophages and NK cells. The detailed mechanism of how volatile anesthetics affect the activity of antitumor cells remains unknown. Thus the investigators will conduct the clinical investigation to study the effect of volatile anesthetics on the immune response and metastasis in patients undergoing colorectal cancer resection, exploring molecular mechanism involved if inhalational anesthetics show an effect. The findings of this study would be valuable for anesthetic regimen guidance of colorectal cancer patients undergoing surgical resection in terms of long-term survival.

Blood of the enrolled patients will be sampled at different time-points for examination of lymphocytes.

The Effects of General Anesthetics on Lymphocytes in Patients Undergoing Colorectal Cancer Resection and Mechanism Involved

Comparison of the Effects of Total Intravenous Anesthesia and Inhalation Anesthesia on Lymphocytes in Patients Undergoing Colorectal Cancer Resection and the Mechanism Involved: a Single-center, Randomized, Prospective Study

Patients receive a reoperation for any reason during hospitalization

The duration of patients stay in hospital

Blood will be drawn preoperatively ( at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing CD4+/CD8+, B lymphocytes, dendritic cells, natural killer cells

Patients who remain alive without known colonal or rectal tumor recurrence

Patients who remain alive with known colonal or rectal tumor recurrence

Patients who remain alive with known colonal or rectal tumor metastasis

Patients who have a surgery under general anesthesia

Total intravenous anesthesia, inhalational anesthesia or combined anesthesia

Patients have radiotherapy for any cancer

Patients have chemotherapy for any cancer

Blood will be drawn preoperatively (at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing circulating tumor cells

Blood will be drawn preoperatively (at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing IL, TNF-α, IFN-γ and GCSF

Blood will be drawn preoperatively (at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing CEA, CA199, GP87 and TPA.

Guizhi Du

Associate Professor

Mouth and Tooth Diseases

Rare Diseases

Tongue Neoplasms

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Tongue Diseases

Tongue Cancer

Oral Cancer

combined intravenous-inhalational anesthesia

intravenous anesthesia

inhalational anesthesia

tiejun zhang, M.D.

kebin Liu

Surgical excision is the mainstay of treatment for tongue cancer. However, surgery-induced immunosuppression has been implicated in the development of post-operative septic complications and neoplasm metastasis. General anesthesia is considered to not only suppress surgical stress, but also affect the immune function directly，such as altering the number and activity of immune cells. It is reported that some anesthetics increase susceptibility to tumor metastasis, apparently by suppressing natural killer cell activity. Different anesthetic techniques and anesthetics used in anesthesia have shown different effects on immunity. Many of the studies were animal trials or performed in vitro; in addition, most are focused on a single drug. To date, there is little published prospective clinical research designed specifically to investigate the effects of different general anesthetic technique on immune function in patients with oral malignant tumors. The aim of this study is going to characterize the immune response of patients undergoing surgery for tongue cancer under 3 types of general anesthesia.

Effects of Different General Anesthesia Methods on Immune Responses in Patients Undergoing Surgery for Tongue Cancer

30 min before induction, 1 h, 3 h and 5 h after induction; at the end of operation and 24h, 48 h and 72 h after operation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anesthetic Technique on Immune Response in Colorectal Cancer	NCT01902849	Colorectal Neop...	blood sampling ...	18 Years -	Iuliu Hatieganu University of Medicine and Pharmacy
The Effects of General Anesthetics on Lymphocytes in Patients Undergoing Colorectal Cancer Resection and Mechanism Involved	NCT03193710	Colorectal Canc... Survival Rate General Anesthe... Lymphocyte Dest... Molecular Mecha...	Propofol Sevoflurane Remifentanil	18 Years - 65 Years	West China Hospital
Anesthetic Technique on Immune Response in Colorectal Cancer	NCT01902849	Colorectal Neop...	blood sampling ...	18 Years -	Iuliu Hatieganu University of Medicine and Pharmacy
Effects of Different General Anesthesia Methods on Immune Responses in Patients Undergoing Surgery for Tongue Cancer	NCT01854021	Tongue Cancer	intravenous ane... combined intrav... inhalational an...	50 Years - 70 Years	Wuhan University

Spots Global Cancer Trial Database for inhalational anesthesia