Changes of serum and peritoneal inflammatory mediators in laparoscopic radical resection for right colon carcinoma.

OBJECTIVE: The objective of this study is to investigate the effects of laparoscopic and open operation on serum and peritoneal inflammatory mediators in patients with right colon carcinoma. PATIENTS AND METHODS:: A total of 100 patients were randomly divided into laparoscopic group (n = 50) and open group (n = 50). The age, sex, operation time, operation blood loss, post-operative Dukes stage, time to first passage of flatus and post-operative hospital stay were recorded. The levels of hypersensitive C reactive protein (hsCRP) and tumour necrosis factor-α (TNF-α) in serum and abdominal exudate were measured by ELISA at the time of pre-operative 2 h and post-operative 6 h and 24 h.
RESULTS: There was no significant difference in age, sex, Dukes stage and pre-operative inflammatory mediators between the two groups (P > 0.05). The operation time, intraoperative blood loss, time to first passage of flatus and post-operative hospital stay were significantly better in laparoscopic group than those in open operation group. At 6 h and 24 h after operation, the levels of hsCRP and TNF-α in serum and abdominal exudate in laparoscopic group were significantly lower than those in open operation group.
CONCLUSIONS: Laparoscopic surgery for the treatment of right colon carcinoma has the advantages of fewer traumas, less systemic and local inflammatory response, rapider post-operative recovery and shorter hospital stay. It is worthy of clinical application.

INTRODUCTION

Colon carcinoma is one of the most common malignant tumours of the digestive tract in China, ranking second in the Chinese gastrointestinal tract.[1] In recent years, with the improvement of people's living standards and changes in diet, the incidence of colon carcinoma was increasing year by year. At present, surgery is still the first choice for the treatment of colon carcinoma and the only way to cure this deadly malignancy. With the results of large-scale clinical randomised study, laparoscopic surgery for malignant tumour cure has been widely recognised. Compared with traditional surgery method, laparoscopic surgery has the advantages of fewer trauma, rapider post-operative recovery, lower incidence of infection and less pain. This study focused on exploring the changes of hypersensitive C reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) in serum and abdominal exudate in patients with right colon carcinoma who undergoing laparoscopic radical resection versus traditional surgery method.

PATIENTS AND METHODS

Patients

From January 2010 to December 2015, patients who diagnosed with the right side colon carcinoma by colonoscopical and pathological analysis were recruited in this study. A total of 100 cases were randomly divided into laparoscopic group (n = 50) and open group (n = 50). There were no significant differences in age, sex, Dukes stage and other general data between the two groups of patients [Table 1].

Table 1

Patients’ characteristics

Variables	Sex (n)		Age (years)	Dukes stage (n)
	Male	Female		A	B	C
Laparoscopic group	26	24	58.26±10.12	12	25	13
Open group	23	27	61.32±9.16	10	18	22
t/χ2	0.43		1.362	0.33
P	0.52		0.075	0.58

Laparoscopic surgical method

Laparoscopic surgery of all the patients was operated by the same surgeon. First, assess the mass for its resectability. Then lift up transverse colon and identify C of duodenum. Just on the inferior side of duodenum make the incision over peritoneum with Harmonic Ace (Ethicon Endosurgery, Cincinnati). Pass a gauze piece, and CO2 itself insufflates in to dissect duodenum and kept away from operative injury. We adopt the medial-to-lateral approach, so the vessels are taken very near to the origin of the superior mesenteric artery with a clearance of lymph nodes. Ileocolic and right branch of middle colic vessels are clipped proximally and on specimen side. True right colic vessels are present only in about 10%–15% of patients.[2] Along the white line of Toldt, mobilise entire right colon with up to mid transverse level. This step is done with care to prevent injury to the right ureter and gonadal vessels. Now, the resection and anastomoses can be done extracorporeally by delivering colon through 5 cm sized incision in the right iliac fossa. The resectional margin of colon should be at least of 5 cm. For specimen removal, we use glove bag so as to prevent contamination of the wound by tumour cells.

Methods for the detection of inflammatory mediators

Peritoneal wash solution collection method

Two hundred and fifty millilitres sterile warm saline was injected into the abdominal cavity, and then, we punctured intraperitoneal flushing fluid in the McIntosh point. By this way, we got the samples before the operation. Samples of abdominal exudate after operation were collected from the abdominal drains. The samples were centrifuged at 5000 rpm for 15 min before being stored at −80°C. The levels of hsCRP and TNF-α were measured by ELISA (Ray BioR Human hsCRP and TNF-α ELISA Kit protocol, Shenggong, Shanghai, China). The procedure was performed as described in the kit.

Statistical analysis

SPSS 19.0 (IBM, Armonk City, New York State, USA) statistical software was used to analyse the data. Measurement data used t-test, and count data comparison and analysis used Chi-square test. P < 0.05 was considered statistically significant.

RESULTS

There was no significant difference in the expression of hsCRP and TNF-α between the two groups in the pre-operative serum and intraperitoneal flushing fluid (P > 0.05). At 6 h and 24 h after operation, the level of inflammatory mediators in abdominal cavity was significantly lower than that in open surgery group (P < 0.05) [Tables 2–5].

Table 2

Serum hypersensitive C reactive protein levels (mg/dL)

Variables	Pre-operative 2 h	Post-operative 6 h	Post-operative 24 h
Laparoscopic group	8.24±0.42	15.36±2.63	12.42±2.56
Open group	9.75±1.30	20.52±3.91	17.98±2.73
t	2.12	4.66	4.87
P	0.482	0.033	0.029

Table 5

Peritoneal tumour necrosis factor-α levels (pg/ml)

Variables	Pre-operative 2 h	Post-operative 6 h	Post-operative 24 h
Laparoscopic group	131.78±22.54	192.35±24.47	176.56±31.65
Open group	138.42±21.58	220.79±22.46	221.45±30.85
T	2.14	6.68	5.21
P	0.089	0.025	0.047

Compared with laparoscopic group, the operation time, intraoperative blood loss, time to first passage of flatus and post-operative hospital stay were better than those of the open group, the difference was statistically significant (P < 0.05) [Table 6].

Table 6

Date of patients undergoing operation for right colon carcinoma

Variables	Operative time (min)	Blood loss (ml)	Time to first passage of flatus (day)	Post-operative hospital stay (day)
Laparoscopic group	205.59±32.88	56.23±22.36	2.32±0.37	9.78±3.12
Open group	120.35±12.35	105.38±27.41	3.83±0.76	14.56±6.34
t	5.26	3.32	4.24	5.48
P	0.044	0.038	0.035	0.023

DISCUSSION

In recent years, laparoscopic radical resection of colorectal surgery has achieved a similar or better short- and long-term efficacy, compared with an open operation. The current laparoscopic technology has been developed rapidly in a number of fields. A lot of studies have shown that laparoscopic colorectal carcinoma radical surgery is effective and safe.[34] Studies showed that compared with open operation, laparoscopic radical resection of colorectal carcinoma can reduce post-operative hospital stay, reduce surgical pain, conducive to post-operative recovery, has fewer effects on the immunity function, with a lower incidence of complications, mortality and post-operative infection rate. C reactive protein (CRP) was mainly secreted by inflammatory mediators such as interleukin-6 and TNF-α in hepatocytes. The half-life of CRP was 4–6 h. After 6–8 h of infection, CRP increased significantly. Moreover, hsCRP had higher sensitivity and comparability. At present, many studies have confirmed hsCRP as a positive acute phase protein,[5] which is a specific marker of inflammatory response syndrome and the most sensitive and specific inflammatory status indicators,[6] hsCRP is widely used in multiple disciplinary areas.[78]

TNF-α, a traditional inflammatory marker, is a cytokine produced by activated macrophages that inhibits osteoblasts and stimulates osteoclasts. TNF-α is thought to be the earliest and most important inflammatory mediator in the inflammatory response process. It can activate neutrophils and lymphocytes in the blood, increase the permeability of vascular endothelial cells and regulate the metabolic activity of other tissues. TNF-α can also regulate the synthesis and release of other cytokines and inhibits the immune response to the body. In this study, hsCRP and TNF-α were used as the index of inflammation to explore the changes of inflammatory mediators in serum and abdominal exudate before and after the operation. The results showed that there was no significant difference in the inflammatory mediators between the two groups before operation. At 6 h after operation, the inflammatory mediators in the blood and abdominal exudate were higher than before in the two groups, which could confirm that the surgical trauma made the body producing a stress response, leading to elevate inflammatory mediators, which inhibited the immune function of patients.[9] However, the levels of hsCRP and TNF-α in laparoscopic group were significantly lower than those in the open group at 6 h and 24 h after operation. The results showed that the local and systemic inflammatory response was lower, and the inhibition of the systemic immune system was lighter in the laparoscopic surgery group than that of the open group.

The results of this study showed that laparoscopic surgery had more advantages towards the open surgery in patients with operation time, bleeding, time to first passage of flatus and post-operative hospital stay, indicating that laparoscopic surgery on the gastrointestinal tract interference is small. Moreover, the gastrointestinal function recovered faster, and the laparoscopic surgery could reduce the occurrence of various complications after surgery, more conducive to the recovery of patients. Young-Fadok et al.[10] reported that laparoscopic colon resection surgery bleeding, post-operative pain response, intestinal function recovery and hospitalisation time were better than the traditional open surgery. Franklin et al.[11] reported 191 cases of laparoscopic and 224 cases of open colorectal carcinoma surgery randomised controlled study, there was no statistically significant in the length of the resected bowel, tumour margin and the number of resected lymph nodes between the two groups. By comparing the laparoscopic and open colonic resection of the surgical specimens, Hoffman et al.[12] found that the number of resected lymph nodes and surgical radical standard difference was not statistically significant, but the resected lymph nodes of the former were more than the latter. However, due to puncture holes, small incision may lead to tumour metastasis, making laparoscopic treatment of malignant tumours to be questioned, more and more scholars believe that by taking protective measures could reduce the occurrence of this complication. On the recurrence rate and long-term effects of the study, through 2 years of follow-up comparison of laparoscopic and open colorectal resection of the rectum, Hartley et al.[13] compared the rate of tumour recurrence, tumour implantation in surgical incision or Troca, and overall survival between the two group. The difference was not statistically significant. Silecchia et al.[14] studied statistics of laparoscopic colorectal carcinoma in the Italian laparoscopic centre for nearly 5 years and found the rate of post-operative incision implantation was 0%–0.2%. Compared with open operation, the difference was not statistically significant. COST(the clinical outcomes of surgical therapy) experiment[15] included 872 cases of colorectal carcinoma from 48 centres, the average follow-up of 4.4 years, showing that there was no statistically significant difference between the two groups on the recurrence rate and survival rate. Abraham et al.[16] meta-analysis showed that there was no statistically significant difference in laparoscopic and open surgery for 3, 5 years’ survival rates and 3, 5 years’ disease-free survival rates.

CONCLUSION

In summary, laparoscopic surgery has the advantages of small trauma, little inflammatory response, rapid rehabilitation, short hospital stay for the treatment of right colon carcinoma. Thus, it is worthy for clinical application.

This work was approved by the Clinical Research and Ethics Committee at the Second Hospital Affiliated to Soochow University and the Institute of Cancer Research.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table 3

Peritoneal hypersensitive C reactive protein levels (mg/dL)

Variables	Pre-operative 2 h	Post-operative 6 h	Post-operative 24 h
Laparoscopic group	8.89±0.63	23.42±2.12	18.23±1.69
Open group	7.15±1.53	27.23±3.26	23.13±1.56
t	1.54	4.36	4.58
P	0.567	0.028	0.036

Table 4

Serum tumour necrosis factor-α levels (pg/ml)

Variables	Pre-operative 2 h	Post-operative 6 h	Post-operative 24 h
Laparoscopic group	110.39±12.89	179.58±25.68	158.75±24.56
Open group	121.35±23.68	215.86±23.46	185.23±24.69
t	1.24	4.58	5.36
P	0.067	0.022	0.043