Stress And The Immune System Biology Essay

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A clinical review explaining and comparing the effects on post operative immune function and stress response due to open vs. laparoscopic surgery on cancer patients

Surgery itself can cause trauma and trigger an immune response to the trauma, specifically the acute phase response.

Comparing laparoscopic and open surgery on cancer patients, it can be concluded that laparoscopic surgery is less invasive and causes less damage to surrounding tissues

Studies show that interleukin-6 (IL-6) and C-reactive protein (CRP) levels rise less in cancer patients that had laparoscopic surgery

The conclusion can be made that laparoscopic surgery should be used for cancer patients in preference to open surgery

Methodology - short

The papers used in this review were found using various online search engines, including Google Scholar and PubMed. The search terms originally used were, "surgery", "stress", "immune", "response" and "cancer". Then the searches were refined using specialist terms such as "carcinoma", "rectal", "resection", "laparoscopic", "IL-6", "C-reactive protein" and "levels", and specific criteria were used to select the papers. Papers were only included in this review if they were written in English and were from well known journals, or were studies that used over 15 patients with non-metastatic gastric, colon or rectal cancer and measured the levels of different cytokines and lymphocytes in the blood. A relevant Cochrane review was found online, as well as a range of papers from journals such as Diseases of the Colon and Rectum and Surgical Endoscopy. Medical textbooks were also used to provide basic understanding of the acute phase immune response. The evidence used in this review is reliable and of a good quality.

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Introduction

Short, no rambling and reference any statements made

State aims and objectives - be specific and show what you will discuss

To briefly mention how surgery can be referred to as a stressor and can cause effects on the immune system

To explain that surgery causes trauma to the body and an appropriate response is initiated.

Explain that the acute phase response occurs after trauma.

Interleukin-6 (IL-6) is a mediator of the acute phase response and C-reactive protein is produced in the acute phase response after trauma and is also triggered by IL-6

To explain how laparoscopic-assisted surgery is thought to cause less trauma to the patient than conventional open surgery methods such as a laparotomy.

Explain what the review is about

The review is

I will discuss how surgery has an effect on the immune response etc.

Discussion

Effects of surgery on the immune response

Surgical trauma can have a dramatic effect on cancer patients when undergoing surgery, and can affect the immune response leading to a depressed immune system. Although cancer patients aren't specifically always immune-suppressed, it's better for all patients to have a good immune system so that they don't suffer from the wide range of infections prevalent in hospitals. A review by Tsamis et al. states that the depression of the immune system is due to the inflammatory response, which occurs in response surgical trauma in an attempt to prevent infection by killing invading microorganisms and to heal the damaged tissue. [1] When carrying out surgery, it is therefore beneficial to try and limit the amount of trauma caused by surgery.

The acute phase response and explain it

"effects on cancer patients - it's better to have less inflammatory response

The studies being compared in this review use patients with cancer that are undergoing surgery, and the patients are split into two groups with almost equal numbers in each; one group has a laparoscopic operation and the other has a laparotomy (open surgery).

Comparing laparoscopy so open surgery on the immune system (results)

Comparing the results of relevant trials and studies

In each trial, blood samples were taken from the patients pre-operatively and were analysed so that the results could be used as a baseline. This meant that they could draw accurate conclusions from the results obtained by analysis of the blood samples taken post-operatively. The blood was analysed to measure a variety of substances, including IL-6, CRP and other lymphocytes. As these substances are involved in the acute phase response, they can give an indication of how the trauma of surgery has affected the immune response.

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In a recent randomised trial by Veenhof et al., [2] the levels of IL-6 and CRP were compared at 2 hrs, 24 hrs and 72 hrs after the operation, which means that they were able to analyse the varying levels over time and their conclusions were more reliable. Veenhof et al.5 measured the patients' pre-operative IL-6 baseline levels to be comparable for both laparoscopic and open surgery groups (p=0.201). After laparoscopic surgery the increase in levels of IL-6 was significantly less than the increase in IL-6 levels after open surgery. However, they recorded no significant difference between the two IL-6 values at

48 hrs and 72 hrs after surgery, and there was also no difference in the rise of CRP levels between the two groups.

Another less recent prospective randomised trial by Leung et al. [3] used 34 patients with rectosigmoid carcinoma, and with demographically compatible data, to investigate the effects of laparoscopic and open resection of the rectosigmoid tumour on postoperative tissue damage. Systemic cytokines were used as markers so blood samples were collected before surgery and at different times after surgery. Blood was taken at 2 hrs, 8 hrs, 24 hrs, 48 hrs, 72 hrs, 1 week and 4 weeks after surgery and was assayed for IL-6 and CRP along with other substances. IL-6 levels peaked in both groups 2 hrs after surgery; however, the laparoscopic group levels were significantly lower than the open group (Fig 1). The patients' CRP levels increased then decreased gradually over the four weeks peaking at 48 hrs, with the laparoscopic group having significantly lower levels of CRP during the four weeks compared to the open group (Fig 2).

Assuming that the amount of surgical trauma directly correlates to IL-6 and CRP levels, and that these cytokine levels directly relate to depression of the immune system, Veenhof et al. and Leung et al. concur with a fairly recent review by Ni Choileain et al. [4] The review states that surgery causes trauma to the body and triggers the acute phase response, which in turn depresses systemic immune function temporarily.

However, another ... study by ... contradicts these results

Reliability of evidence

Most of the evidence found on this subject was published between 2000 and 2003, with some also being published from as early as 1997 up until 2010, which shows that changes in the immune response due to laparoscopic surgery is still a relevant topic for researchers to analyse. The papers that are older than 10 years have still been used in this review but aren't as reliable due to a lack of new technologies.

All of papers use patients with similar characteristics, for example, patients with an age of over 40 years and without advanced or metastatic cancer. Research [done by...] has shown that there are higher levels of IL-6 in patients with advanced or metastatic cancer [5] ; however, as the papers in this review excluded patients with metastasis from their studies they are more reliable.

Overall, the papers used in this review were published trials or studies in journals, meaning that their results could be quoted accurately in this review as they are reliable and valid. Therefore, the conclusion can be made that laparoscopic surgery on cancer patients causes less trauma than conventional open surgery and hence causes the immune system to be depressed, leaving the patient more susceptible to opportunistic infections. This is relevant in clinical application as surgeons could be advised to perform more laparoscopic surgery on cancer patients, and this could essentially improve morbidity over the duration of hospital admission.

Final overview of what you think and where the field stands (any ideas of clinical application?)

Tables and Figures

Fig 2. A graph to show the average levels of C-reactive protein over the course of 4 weeks after undergoing laparoscopic and open resection of rectosigmoid carcinoma.

Fig 1. A graph to show the average levels of interleukin-6 over the course of 72 hours after undergoing laparoscopic and open resection of rectosigmoid carcinoma.

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