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 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

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

Validation of a modified clinical risk score to predict cancer-specific survival for stage II colon cancer

Many patients with stage II colon cancer will die of their disease despite curative surgery. Therefore, identification of patients at high risk of poor outcome after surgery for stage II colon cancer is desirable. This study aims to validate a clinical risk score to predict cancer-specific survival in patients undergoing surgery for stage II colon cancer. Patients undergoing surgery for stage II colon cancer in 16 hospitals in the West of Scotland between 2001 and 2004 were identified from a prospectively maintained regional clinical audit database. Overall and cancer-specific survival rates up to 5 years were calculated. A total of 871 patients were included. At 5 years, cancer-specific survival was 81.9% and overall survival was 65.6%. On multivariate analysis, age ≥75 years (hazard ratio (HR) 2.11, 95% confidence intervals (CI) 1.57–2.85; P<0.001) and emergency presentation (HR 1.97, 95% CI 1.43–2.70; P<0.001) were independently associated with cancer-specific survival. Age and mode of presentation HRs were added to form a clinical risk score of 0–2. The cancer-specific survival at 5 years for patients with a cumulative score 0 was 88.7%, 1 was 78.2% and 2 was 65.9%. These results validate a modified simple clinical risk score for patients undergoing surgery for stage II colon cancer. The combination of these two universally documented clinical factors provides a solid foundation for the examination of the impact of additional clinicopathological and treatment factors on overall and cancer-specific survival

Factors associated with the efficacy of polyp detection during routine flexible sigmoidoscopy

Objective: Flexible sigmoidoscopy reduces the incidence of colonic cancer through the detection and removal of premalignant adenomas. However, the efficacy of the procedure is variable. The aim of the present study was to examine factors associated with the efficacy of detecting polyps during flexible sigmoidoscopy. Design and patients: Retrospective observational cohort study of all individuals undergoing routine flexible sigmoidoscopy in NHS Greater Glasgow and Clyde from January 2013 to January 2016. Results: A total of 7713 patients were included. Median age was 52 years and 50% were male. Polyps were detected in 1172 (13%) patients. On multivariate analysis, increasing age (OR 1.020 (1.016–1.023) p<0.001), male sex (OR 1.23 (1.10–1.38) p<0.001) and the use of any bowel preparation (OR 3.55 (1.47–8.57) p<0.001) were associated with increasing numbers of polyps being detected. There was no significant difference in the number of polyps found in patients who had received an oral laxative preparation compared with an enema (OR 3.81 (1.57–9.22) vs 3.45 (1.43–8.34)), or in those who received sedation versus those who had not (OR 1.00 vs 1.04 (0.91–1.17) p=0.591). Furthermore, the highest number of polyps was found when the sigmoidoscope was inserted to the descending colon (OR 1.30 (1.04–1.63)). Conclusions: Increasing age, male sex and the utilisation of any bowel preparation were associated with an increased polyp detection rate. However, the use of sedation or oral laxative preparation appears to confer no additional benefit. In addition, the results indicate that insertion to the descending colon optimises the efficacy of flexible sigmoidoscopy polyp detection

How and why systemic inflammation worsens quality of life in patients with advanced cancer

Introduction: The presence of an innate host systemic inflammatory response has been reported to be a negative prognostic factor in a wide group of solid tumour types in both the operable and advanced setting, both local and distant. In addition, this host systemic inflammatory response is associated with both clinician reported patient performance status and self-reported measures of quality of life in patients with cancer. Areas covered: A variety of mechanisms are thought to underlie this, including the influence of the host immune response on physical symptoms such as pain and fatigue, its effect on organ systems associated with physical ability and well being such as skeletal muscle, and bone marrow. Furthermore, this innate inflammatory response is thought to have a direct negative impact on mood through its action on the central nervous system. Expert commentary: It is clear that the host systemic inflammatory response represents a target for intervention in terms of both improving quality of life and prognosis in patients with advanced cancer. Based on this paradigm, future research should focus both on pathways which might be targeted by novel agents, but also on whether existing anti-inflammatory drugs might be of benefit

Systemic inflammation predicts all-cause mortality: a Glasgow Inflammation Outcome Study

Introduction: Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.<p></p> Methods: Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×109/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.<p></p> Results: In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality. Conclusion The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality

Clinicopathological determinants of an elevated systemic inflammatory response following elective potentially curative resection for colorectal cancer

Introduction: The postoperative systemic inflammatory response (SIR) is related to both long- and short-term outcomes following surgery for colorectal cancer. However, it is not clear which clinicopathological factors are associated with the magnitude of the postoperative SIR. The present study was designed to determine the clinicopathological determinants of the postoperative systemic inflammatory response following colorectal cancer resection. Methods: Patients with a histologically proven diagnosis of colorectal cancer who underwent elective, potentially curative resection during a period from 1999 to 2013 were included in the study (n = 752). Clinicopathological data and the postoperative SIR, as evidenced by postoperative Glasgow Prognostic Score (poGPS), were recorded in a prospectively maintained database. Results: The majority of patients were aged 65 years or older, male, were overweight or obese, and had an open resection. After adjustment for year of operation, a high day 3 poGPS was independently associated with American Society of Anesthesiologists (ASA) grade (hazard ratio [HR] 1.96; confidence interval [CI] 1.25–3.09; p = 0.003), body mass index (BMI) (HR 1.60; CI 1.07–2.38; p = 0.001), mGPS (HR 2.03; CI 1.35–3.03; p = 0.001), and tumour site (HR 2.99; CI 1.56–5.71; p < 0.001). After adjustment for year of operation, a high day 4 poGPS was independently associated with ASA grade (HR 1.65; CI 1.06–2.57; p = 0.028), mGPS (HR 1.81; CI 1.22–2.68; p = 0.003), NLR (HR 0.50; CI 0.26–0.95; p = 0.034), and tumour site (HR 2.90; CI 1.49–5.65; p = 0.002). Conclusions: ASA grade, BMI, mGPS, and tumour site were consistently associated with the magnitude of the postoperative systemic inflammatory response, evidenced by a high poGPS on days 3 and 4, in patients undergoing elective potentially curative resection for colorectal cancer

The relationship between tumour budding, the tumour microenvironment and survival in patients with primary operable colorectal cancer

Background: Tumour budding has been reported to reflect invasiveness, metastasis and unfavourable prognosis in colorectal cancer. The aim of the study was to examine the relationship between tumour budding and clinicopathological characteristics, tumour microenvironment and survival in patients with primary operable colorectal cancer. Methods: A total of 303 patients from a prospective data set of patients with primary operable colorectal cancer were included in the study. The presence of budding was determined through assessment of all tumour-containing H&E slides and the number of tumour buds was counted using a 10 high-powered field method. Routine pathologic sections were used to assess: tumour necrosis, the tumour inflammatory cell infiltrate using Klintrup–Makinen (KM) grade and tumour stroma percentage (TSP) combined as the Glasgow Microenvironment Score (GMS). Results: High-grade tumour budding was present in 39% of all tumours and in 28% of node-negative tumours respectively. High-grade budding was significantly associated with T stage (P<0.001), N stage (P<0.001), TNM stage (P<0.001), serosal involvement (P<0.001), venous invasion (P<0.005), KM grade (P=0.022), high tumour stroma (P<0.001) and GMS (P<0.001). Tumour budding was associated with reduced cancer-specific survival (CSS) (HR=4.03; 95% confidence interval (CI), 2.50–6.52; P<0.001), independent of age (HR=1.47; 95% CI, 1.13–1.90; P=0.004), TNM stage (HR=1.52; 95% CI, 1.02–2.25; P=0.040), venous invasion (HR=1.73; 95% CI, 1.13–2.64; P=0.012) and GMS (HR=1.54; 95% CI, 1.15–2.07; P=0.004). Conclusions: The presence of tumour budding was associated with elements of the tumour microenvironment and was an independent adverse prognostic factor in patients with primary operable colorectal cancer. Specifically high tumour budding stratifies effectively the prognostic value of tumour stage, venous invasion and GMS. Taken together, tumour budding should be assessed routinely in patients with primary operable colorectal cancer