Effect of anaesthetic agents on immuno-inflammatory response of breast cancer

Background

 In India, breast cancer is the most prevalent cancer form among women which accounted for 1,62,468 new incidences and 87,090 deaths in 2018 (“Breast Cancer - India Against Cancerâ€). At our hospital, we have done total of 1270 cases of mastectomy in last five years, left behind number of inoperable cases. More than 90 % of the women diagnosed with breast cancer (Stage I, II and III) undergo surgery and it is important to decipher how the peri-operative management may affect the outcome. During the peri-operative period, surgery induced stress responses and anaesthetic-induced immune suppression may play a critical role in establishment and growth of metastatic lesions. A lot of literature reviews support this claim of role of anaesthetic technique on balance between pro-tumour and tumour-resisting factors and thus facilitation breast cancer recurrence or metastasis. Maximum studies reported till date are retrospective study and none in Indian scenario.

This is an investigator initiated, prospective and comparative study proposal form the Department of Anesthesiology ,where a pilot project on the subject stated above with assistance of research wing of the Institute is proposed, the result of which may indicate a change in mode of anesthesia in case of cancer surgery in future.

 Scope of Work

 There are no human studies on the isolated effect of volatile anaesthetics on tumour metastasis. Since inhaled anaesthetics have direct and indirect effects on different aspects of the immune response, it is reasonable to assert that they are important factors for postoperative immune suppression and residual malignant cell migration and invasion (Laudanski et al. 2016).Although no optimal anaesthetic combination has been identified for patients undergoing breast cancer resection, Eden et al. in 2018 proposed that an ideal anaesthetic in the breast cancer patient population would involve a combination of total intravenous anaesthesia (TIVA) (propofol), regional anaesthesia (para-vertebral block), non-opioid sedatives (clonidine or dexmedetomidine), and COX-2 inhibition (ketorolac) (Eden et al. 2018). At present in India there are no prospective studies on comparative analysis of isoflurane and propofol with reference to immune suppression, inflammation and tumour recurrence in peri-operative breast cancer patients. With this background it would interesting to compare the effect of isoflurane and propofol on immune suppression, inflammation and metastasis in perioperative breast cancer patients.

Objective

To compare the effects of two different anaesthetic agents, Isoflurane and Propofol in peri-operative settings of carcinoma breast, those are evident by the alteration of the following three biological markers-

1.    Immune phenotype of peripheral blood lymphocytes (CD4, CD8, CD19, CD56)

2.    Expression of serum inflammatory markers (TNF-a, IL-6, IL-8, IL-10)

3.    Activity of serum matrix metalloproteinase (MMP-2 and MMP-9)

Subjects/samples

Selection of participants

The newly diagnosed breast cancer patients will be asked to participate in the study. Informed consent in either of the three vernaculars- English, Bengali or Hindi will be obtained from each participant. The demographic information will be obtained with screening form and participants will be chosen according to inclusion and exclusion criteria.

 Inclusion Criteria

1. Age between 18-65 yrs (both inclusive)

2. Newly diagnosed breast cancer (Unilateral) confirmed with histopathological     diagnosis.

3. ASA I (Normal healthy patient) & ASA II (Patient with mild systemic disease)

4. T1 N0, T2N0, T3N0, T1N1, T2N1, T3N1 Mx

5. Both male & female

6. Duration of surgery ≤ to 2 hrs.

 Exclusion Criteria

1. Patient having any kind of anticancer treatment

2. Active bleeding

3. Recent history of massive blood transfusion

4. Pregnant & Lactating woman

 The patients will be randomized to Arm-A & Arm-B according to a computer generated random number table and will be assigned to receive either propofol infusion or isoflurane inhalation for maintenance of anaesthesia.

Collection of blood samples

Venous blood samples (5 ml) will be collected after obtaining informed consent, from ante-cubital vein in ‘vacutainer’ tubes (BD, USA) without anticoagulant. For serum, the blood will be anti-coagulated with K2EDTA. Blood samples will be collected 1day before surgery, during surgery (1 hr after incision) and 48 hours after surgery. Blood samples will be drawn by persons authorized to do phlebotomy (clinicians / technicians of CNCI hospital).