Increased oxidative stress with substantial dysregulation of genes related to oxidative stress and DNA repair after laparoscopic colon cancer surgery.

Surgical stress is followed by oxidative stress, where reactive oxygene species may act as regulators of pathways related to cancer cell survival and metastatic ability. Furthermore, reactive oxygene species may cause DNA and RNA damage. The aim of this study was to examine whether laparoscopic colon cancer surgery causes oxidative stress and dysregulation of related pathways. METHODS: Patients undergoing elective laparoscopic surgery for colon cancer were included. Blood and urine samples were drawn on the day prior to surgery and on day 1 and 10 after surgery. RESULTS: Twenty-six patients were included. Out of 140 genes previously identified as sensitive to regulation by reactive oxygene species, 46 were significantly differentially expressed on day 1 after surgery (FDR < 0.05). Upregulated genes were related to cellular immune suppression, proliferation, migration and epithelial to mesenchymal transition. Downregulated genes were related to IFN pathways and cytotoxic immunological reactions. Genes related to DNA repair were primarily downregulated on day one after surgery, and urinary excretion of 8oxdG was decreased on day two after (p = 0.004), and increased on day 10 after surgery (p = 0.01). CONCLUSION: Laparoscopic colon cancer surgery causes oxidative stress, and impaired DNA repair. Gene expression profiling indicates that reactive oxygen species may act as regulators of pathways related to increased risk of metastasis and cellular immune suppression after surgery. Measures of intracellular oxidative stress, indicates impaired DNA repair on day two after surgery, and sustained oxidative stress on day 10 after surgery.

CDX2 expression and perioperative patient serum affects the adhesion properties of cultured colon cancer cells.

BACKGROUND: Colon cancer is one of the most commonly diagnosed types of cancer with surgical resection of the tumor being the primary choice of treatment. However, the surgical stress response induced during treatment may be related to a higher risk of recurrence. The aim of this study was to examine the effect of surgery on adhesion of cultured colon cancer cells with or without expression of the tumour suppressor CDX2. METHOD: We enrolled 30 patients undergoing elective, curatively intended laparoscopic surgery for colon cancer in this study. Blood samples were drawn 1 day prior to surgery and 24 h after surgery. The samples of pre- and postoperative serum was applied to wild type colon cancer LS174T cells and CDX2 inducible LS174T cells and adhesion was measured with Real-Time Cell-Analysis iCELLigence using electrical impedance as a readout to monitor changes in the cellular adhesion. RESULTS: Adhesion abilities of wild type LS174T cells seeded in postoperative serum was significantly increased compared to cells seeded in preoperative serum. When seeding the CDX2 inducible LS174T cells without CDX2 expression in pre- and postoperative serum, no significant difference in adhesion was found. However, when inducing CDX2 expression in these cells, the adhesion abilities in pre- and postoperative serum resembled those of the LS174T wild type cell line. CONCLUSIONS: We found that the adhesion of colon cancer cells was significantly increased in postoperative versus preoperative serum, and that CDX2 expression affected the adhesive ability of cancer cells. The results of this study may help to elucidate the pro-metastatic mechanisms in the perioperative phase and the role of CDX2 in colon cancer metastasis.

Whole Blood Gene Expression Profiling in patients undergoing colon cancer surgery identifies differential expression of genes involved in immune surveillance, inflammation and carcinogenesis.

INTRODUCTION: Cancer surgery may represent a potential risk of enhanced growth and metastatic ability of residual cancer cells due to post-operative immune dysfunction. This study identifies changes in transcription of genes involved in immune surveillance, immune suppression and carcinogenesis in the post-operative period of laparoscopic colon-cancer surgery within an ERAS regime. METHODS: Patients undergoing elective, curatively intended laparoscopic surgery for colon cancer stage I-III UICC were included in the study. Patients followed standard of care in an ERAS setting. Whole blood gene expression profiling (WBGP) was performed on the day prior to surgery and 1, 2, 3 and 10-14 days after surgery. Samples were collected in Paxgene tubes and Labeled cDNA was fragmented and hybridized to Affymetrix GeneChip™ 2.0. Results were corrected for multiple hypothesis testing using the false discovery rate. Pathway analysis was performed through the Molecular Signature Database. Paired fold changes of gene expression were calculated for post-operative compared to pre-operative samples. A mixed effect model was used to test differential gene expression by repeated-measures ANOVA. RESULTS: WBGP of 33,804 genes at five timepoints in six patients showed 302 significantly differentially expressed genes between samples from the day prior to surgery and the day after surgery. Pathway gene enrichment analysis showed a downregulation of immunologically relevant pathways. There was a significant downregulation of genes involved in T-cell receptor signaling, antigen presentation and NK-cell activity after surgery. Furthermore, there was an upregulation of cytokines related to metastatic ability, growth and angiogenesis. CONCLUSION: Whole blood gene expression profiling revealed dysregulation of genes involved in immune surveillance, inflammation and carcinogenesis, after laparoscopic colon cancer surgery.

Reduced Rate of Dehiscence After Implementation of a Standardized Fascial Closure Technique in Patients Undergoing Emergency Laparotomy.

OBJECTIVE: In elective surgery, it is well documented that a midline laparotomy should be closed with a slowly absorbable monofilament suture material in a continuous technique, in a ratio of at least 4 : 1. The evidence concerning the suture material or suturing technique in the emergency setting is lacking. We aimed to investigate whether this technique would reduce the rate of dehiscence. METHODS: A standardized procedure of closing the midline laparotomy by using a "small steps" technique of continuous suturing with a slowly absorbable (polydioxanone) suture material in a wound-suture ratio of minimum 1 : 4 was introduced in June 2014. All patients scheduled for any gastrointestinal emergency midline laparotomy were included until October 2015. Pre-, intra-, and postoperative data were registered. All emergency laparotomies performed from 2009 to 2013 served as reference. Chi-squared tests and multivariate Cox regression analysis were performed. RESULTS: We included 494 patients from 2014 to 2015 and 1079 patients from our historical cohort for comparison. All patients had a midline laparotomy in an emergency setting. The rate of dehiscence was reduced from 6.6% to 3.8%, P = 0.03 comparing year 2009 to 2013 with 2014 to 2015. Factors associated with dehiscence were male gender [hazard ratio (HR) 2.8, 95% confidence interval (95% CI) (1.8-4.4), P < 0.001], performance status ≥3 [HR 2.1, 95% CI (1.2-3.7), P = 0.006], cirrhosis [HR 3.8, 95% CI (1.5-9.5), P = 0.004], and retention sutures [HR 2.8, 95% CI (1.6-4.9), P < 0.000]. The 30-day mortality rate was 18.4% in the standardized group vs 22.4% in 2009 to 2013, P = 0.057 and 90-day mortality 24.2% vs 30.4%, P = 0.008. CONCLUSION: The standardized procedure of closing the midline laparotomy by using a "small steps" technique of continuous suturing with a slowly absorbable (polydioxanone) suture material reduces the rate of fascial dehiscence.

Morbidity and mortality rates after emergency abdominal surgery: an analysis of 4346 patients scheduled for emergency laparotomy or laparoscopy.

PURPOSE: Emergency abdominal surgery results in a high rate of post-operative complications and death. There are limited data describing the emergency surgical population in details. We aimed to give a detailed analyses of complications and mortality in a consecutive group of patients undergoing acute abdominal surgery over a 4-year period. METHODS: This observational study was conducted between 2009 and 2013 at Copenhagen University Hospital Herlev, Denmark. All patients scheduled for emergency laparotomy or laparoscopy were included. Pre-, intra-, and post-operative data were collected from medical records. Complications were registered according to the Clavien-Dindo classification. Cox regression analysis was performed to identify risk factors for mortality. RESULTS: A total of 4,346 patients underwent emergency surgery, of whom 14 % had surgical complications and 23 % medical complications. The overall 30-day mortality was 8 % with 50 % of those in this group over 80 years of age. The 30-day mortality rates were 0.8 % (95 % CI 0.5-1.1) and 17 % (95 % CI 15.5-18.9), respectively, for the laparoscopy and the laparotomy groups. The overall death rate within 24 h of surgery was 21 %. Several risk factors for 30- and 90-day mortality were identified: age, ASA ≥3 (American Society of Anaesthesiologists physical status classification), performance score (Zubroed/WHOclassification), cirrhosis of the liver, chronic nephropathy, several medical conditions, and malignancy. CONCLUSION: Almost one in five patients died after emergency laparotomy, of whom one in five died within 24 h of surgery. Predictors for poor outcome were identified.

No Circadian Variation in Surgeons' Ability to Diagnose Acute Appendicitis.

OBJECTIVE: To examine if there were circadian variations in surgeons' ability to diagnose acute appendicitis. DESIGN: Retrospective database study of all patients admitted to an acute surgical procedure under the potential diagnosis of acute appendicitis in a 4-year period. The day was divided into 2 time intervals, day to evening hours (08:00-23:59) and night hours (00:00-07:59). Relevant data regarding the admission and surgical procedures were categorized into these 2 time intervals. SETTING: Department of Surgery at a Danish university hospital in Copenhagen. PARTICIPANTS: A total of 2366 patients were included. There were no age limitations or selection in sex. RESULTS: There was no significant difference in the ability to diagnose appendicitis in day-evening hours vs night hours (p = 0.391), nor was any significant difference found on weekdays (Monday-Thursday) vs weekends (Friday-Sunday) (p = 0.278). There were no differences in duration of the procedures, rate of conversion, or severity of postoperative surgical complications between the 2 groups. More patients underwent diagnostic imaging during day to evening hours compared with night hours (308 vs 46; p = 0.014). The use of imaging had no effect on the ability to diagnose appendicitis. Male sex showed a higher probability of the diagnosis being appendicitis compared with other or no pathology (odds ratio: 3.094; p < 0.001). Age between 40 and 80 years was significantly associated with a higher probability of the diagnosis being appendicitis compared with other or no pathology. The negative appendectomy rate was 10.5%. CONCLUSION: We found no difference in the surgeons' ability to diagnose acute appendicitis during night hours compared with day to evening hours.

[Improved immunologic response after laparoscopic versus open colorectal cancer surgery]. / Bedre immunfunktion efter laparoskopisk end efter åben kolorektal cancer-kirurgi.

Laparoscopic colorectal cancer surgery results in a reduced impact on the immune system compared with open surgery. This is important when taken into consideration that the immune system may have an instrumental role in the advancement of cancer in the perioperative period. Several studies have shown that the perioperative period is characterized by an immune incompetent period, which is believed to favour tumour metastasis. In this paper factors associated with the cellular and innate immune response in relation to laparoscopic and open colorectal cancer surgery are reviewed.