The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

Current focus in colorectal cancer management is on reducing overall mortality by increasing the number of early stage cancers diagnosed and treated with curative intent. Despite the success of screening programmes in down-staging colorectal cancer, interval cancer rates are substantial and other strategies are desirable. Sporadic colorectal cancer is largely associated with lifestyle factors including diet. Polyphenols are phytochemicals ingested as part of a normal diet which are abundant in plant foods including fruits/berries and vegetables. These may exert their anti-carcinogenic effects via the modulation of inflammatory pathways. Key signal transduction pathways are fundamental to the association of inflammation and disease progression including those mediated by NF-κB and STAT, PI3K and COX. Our aim was to examine the evidence for the effect of dietary polyphenols intake on tumour and host inflammatory responses to determine if polyphenols may be effective as part of a dietary intervention. There is good epidemiological evidence of a reduction in colorectal cancer risk from case-control and cohort studies assessing polyphenol intake. It would be premature to suggest a major public health intervention to promote their consumption however, dietary change is safe and feasible, emphasising the need for further investigation of polyphenols and colorectal cancer risk

The role of perineural invasion in predicting survival in patients with primary operable colorectal cancer: a systematic review

Perineural invasion is a clear route for cancer cell spread however, the role of nerves in cancer progression is relatively unknown. Recent work would suggest that nerves can actively infiltrate the tumour microenvironment and stimulate cancer cell growth. Therefore, the aim of the present study was to systematically review the identification and associations of perineural invasion and survival in patients with primary operable colorectal cancer. From initial search results of 912 articles, 38 studies were selected. Using H&E stains; five studies including 1835 patients reported on survival stratified by perineural invasion in colon cancer with weighted average detection rates of 26%; eleven studies including 3837 patients reported on rectal cancer with weighted average detection rates of 25% and; sixteen studies including 9145 patients reported on survival stratified by perineural invasion in colorectal cancer with weighted average detection rates of 17%. Using special techniques (S100), six studies including 1458 patients reported on the identification of perineural invasion in colorectal cancer. In comparison to H&E staining alone, the use of immunohistochemistry with S100 increased the detection of perineural invasion to approximately 70%. However, those studies did not examine the relationship with outcomes, so further research is required to establish the clinical significance of perineural invasion detected by immunohistochemistry. In conclusion, perineural invasion deserves special attention for improved prognostic stratification in patients with colorectal cancer. Further work is required to standardise pathology assessment and reporting of perineural invasion, in particular its definition, use of special stains and routine inclusion in pathology practice. Reliable assessment is required for investigations into mechanisms of perineural invasion, its role tumour spread and prognostic value

The relationship between cardiopulmonary exercise test variables, the systemic inflammatory response, and complications following surgery for colorectal cancer

Background: Both preoperative cardiopulmonary exercise test (CPET)-derived measures of fitness and postoperative C-reactive protein (CRP) concentrations are associated with complications following surgery for colorectal cancer. The aim of the present pilot study was to examine the relationship between CPET and postoperative CRP concentrations in this patient group. Methods: Patients who had undergone CPET prior to elective surgery for histologically confirmed colorectal cancer in a single centre between September 2008 and April 2017 were included. Preoperative VO2 at the anaerobic threshold (AT) and peak exercise were recorded, along with preoperative modified Glasgow Prognostic Score (mGPS) and CRP on each postoperative day. Results: Thirty-eight patients were included. The majority were male (30, 79%), over 65 years old (30, 79%), with colonic cancer (23, 61%) and node-negative disease (24, 63%). Fourteen patients (37%) had open surgery and 24 (63%) had a laparoscopic resection. A progressive reduction in VO2 at peak exercise was significantly associated with both increasing American Society of Anesthesiology (ASA) grade (median, ml/kg/min: ASA 1 = 22, ASA 2 = 19, ASA 3 = 15, ASA 4 = 12, p = 0.014) and increasing mGPS (median, ml/kg/min: mGPS 0 = 18, mGPS 1 = 16, mGPS 2 = 14, p = 0.039) There was no significant association between either VO2 at the AT or peak exercise and postoperative CRP. Conclusions: The present pilot study reports a possible association between preoperative CPET-derived measures of exercise tolerance, and the preoperative systemic inflammatory response, but not postoperative CRP in patients undergoing surgery for colorectal cancer

The impact of preoperative dexamethasone on the magnitude of the postoperative systemic inflammatory response and complications following surgery for colorectal cancer

Background: The magnitude of the postoperative systemic inflammatory response (SIR), as evidenced by C-reactive protein (CRP), is associated with both short- and long-term outcomes following surgery for colorectal cancer. The present study examined the impact of preoperative dexamethasone on the postoperative SIR and complications following elective surgery for colorectal cancer. Methods: Patients who underwent elective surgery, with curative intent, for colorectal cancer at a single center between 2008 and 2016 were included (n = 556) in this study. Data on the use of preoperative dexamethasone were obtained from anesthetic records, and its impact on CRP on postoperative days (PODs) 3 and 4, as well as postoperative complications, was assessed using propensity score matching (n = 276). Results: In the propensity score-matched cohort, preoperative dexamethasone was associated with fewer patients exceeding the established CRP threshold of 150 mg/L on POD 3 (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.26–0.70, p < 0.001) and fewer postoperative complications (OR 0.53, 95% CI 0.33–0.86, p = 0.009). Similar results for both POD 3 CRP and complications were observed when using propensity score-adjusted regression (OR 0.40, 95% CI 0.28–0.57 and OR 0.57, 95% CI 0.41–0.80, respectively) and propensity score stratification (OR 0.41, 95% CI 0.25–0.57 and OR 0.53, 95% CI 0.33–0.86, respectively). Conclusions: Preoperative dexamethasone was associated with a lower postoperative SIR and fewer complications following elective surgery for colorectal cancer

Enhanced recovery after surgery

Enhanced Recovery or Fast Track Recovery after Surgery protocols (ERAS) have significantly changed perioperative care following colorectal surgery and are promoted as reducing the stress response to surgery. The present systematic review aimed to examine the impact on the magnitude of the systemic inflammatory response (SIR) for each ERAS component following colorectal surgery using objective markers such as C-reactive protein (CRP) and interleukin-6 (IL-6). A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2015. Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or IL-6. Nineteen studies, including 1898 patients, were included. Fourteen studies (1246 patients) examined the impact of laparoscopic surgery on the postoperative markers of SIR. Ten of these studies (1040 patients) reported that laparoscopic surgery reduced postoperative CRP. One study (53 patients) reported reduced postoperative CRP using opioid-minimising analgesia. One study (142 patients) reported no change in postoperative CRP following preoperative carbohydrate loading. Two studies (108 patients) reported conflicting results with respect to the impact of goal-directed fluid therapy on postoperative IL-6. No studies examined the effect of other ERAS components, including mechanical bowel preparation, antibiotic prophylaxis, thromboprophylaxis, and avoidance of nasogastric tubes and peritoneal drains on markers of the postoperative SIR following colorectal surgery. The present systematic review shows that, with the exception of laparoscopic surgery, objective evidence of the effect of individual components of ERAS protocols in reducing the stress response following colorectal surgery is limited

The relationship between systemic inflammation and stoma formation following anterior resection for rectal cancer: a cross-sectional study

Introduction: There is evidence that temporary defunctioning stoma formation in patients undergoing anterior resection reduces the risk of anastomotic leakage. The aim of the present study was to investigate the relationship between stoma formation, the postoperative systemic inflammatory response and complications following anterior resection for rectal cancer. Methods: Data was recorded prospectively for patients who underwent anterior resection for histologically proven rectal cancer, from 2008 to 2015 at a single centre, n = 167. Patients had routine preoperative and postoperative blood sampling including serum C-reactive protein (CRP). Postoperative complications including anastomotic leakage were recorded. Results: Of the 167 patients, the majority were male (61%) and over 65 years old (56%) with node negative disease (60%). 36 patients (22%) underwent preoperative neoadjuvant treatment. 100 patients (60%) had a stoma formed at the time of surgery. Stoma formation was significantly associated with male sex (69% vs. 50%, p = 0.017), neoadjuvant chemoradiotherapy (30% vs 9%, p = 0.001) and open surgery (71% vs. 55%, p = 0.040). Of those 100 patients who had a stoma formed, 80 had it reversed. Permanent stoma was significantly associated with increasing age (p = 0.011), exceeding the established CRP threshold of 150 mg/L on postoperative day 4 (67% vs 37%, p = 0.039), higher incidence of postoperative complications (76% vs 47%, p = 0.035), anastomotic leakage (24% vs 2%, p = 0.003) and higher Clavien Dindo score (p = 0.036). Conclusions: There was no significant association between stoma formation during anterior resection and the postoperative systemic inflammatory response. However, in these patients both the postoperative systemic inflammatory response and complications were associated with permanent stoma

Attitudes of surgeons to the use of postoperative markers of the systemic inflammatory response following elective surgery

Background: Cancer is responsible for 7.6 million deaths worldwide and surgery is the primary modality of a curative outcome. Postoperative care is of considerable importance and it is against this backdrop that a questionnaire based study assessing the attitudes of surgeons to monitoring postoperative systemic inflammation was carried out. Method: A Web based survey including 10 questions on the “attitudes of surgeons to the use of postoperative markers of the systemic inflammatory response following elective surgery” was distributed via email. Two cohorts were approached to participate in the survey. Cohort 1 consisted of 1092 surgeons on the “Association of Coloproctology of Great Britain and Ireland (ACPGBI)” membership list. Cohort 2 consisted of 270 surgeons who had published in this field in the past as identified by two recent reviews. A reminder email was sent out 21 days after the initial email in both cases and the survey was closed after 42 days in both cases. Result: In total 29 surgeons (2.7%) from cohort 1 and 40 surgeons (14.8%) from cohort 2 responded to the survey. The majority of responders were from Europe (77%), were colorectal specialists (64%) and were consultants (84%) and worked in teaching hospitals (54%) and used minimally invasive techniques (87%). The majority of responders measured CRP routinely in the post-operative period (85%) and used CRP to guide their decision making (91%) and believed that CRP monitoring should be incorporated into postoperative guidelines (81%). Conclusion: Although there was a limited response the majority of surgeons surveyed measure the systemic inflammatory response following elective surgery and use CRP measurements together with clinical findings to guide postoperative care. The present results provide a baseline against which future surveys can be compared

On the convergence of the chi square and noncentral chi square distributions to the normal distribution

A simple and novel asymptotic bound for the maximum error resulting from the use of the central limit theorem to approximate the distribution of chi square and noncentral chi square random variables is derived. The bound enables the quick calculation of the number of degrees of freedom required to ensure a given approximation error, and is significantly tighter than bounds derived using the Berry-Esseen theorem. An application to widely-used approximations for the decision probabilities of energy detectors is also provided

Voting rule optimisation for double threshold energy detector-based cognitive radio networks

The method by which individual decisions are combined in cooperative cognitive radio networks is crucial to minimising the overall probabilities of false alarm and missed detection. In this paper, general expressions for these probabilities are derived for a double threshold energy detector-based network, and an analytical solution for the optimal value of voting rule is found so that the overall probability of error is minimised. Simulation results show that there are significant advantages to the use of double threshold energy detector-based networks as opposed to their single threshold-based counterparts; additional simulations verify that the analytical solution is optimal