The prognostic value of systemic inflammation in patients undergoing surgery for colon cancer: comparison of composite ratios and cumulative scores.

INTRODUCTION: The systemic inflammatory response has been proven to have a prognostic value. There are two methods of assessing the systemic inflammatory response composite ratios (R) and cumulative scores (S). The aim of this study was to compare the prognostic value of ratios and scores in patients undergoing surgery for colon cancer. METHODS: Patients were identified prospectively in a single surgical unit. Preoperative neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, CRP (C) and albumin (A) levels were recorded. The relationship between composite ratios neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein albumin ratio (CAR) and the cumulative scores neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil- platelet score (NPS), modified Glasgow prognostic score (mGPS) and clinicopathological characteristics, cancer-specific survival (CSS) and overall survival (OS), were examined. RESULTS: A total of 801 patients were examined. When adjusted for tumour node metastasis (TNM) stage, NLR >5 (p < 0.001), NLS (p < 0.01), PLS (p < 0.001), LMR <2.4 (p < 0.001), LMS (p < 0.001), NPS (p < 0.001), CAR >0.22 (p < 0.001) and mGPS (p < 0.001) were significantly associated with CSS. In patients undergoing elective surgery (n = 689), the majority of the composite ratios/scores correlated with age (p < 0.01), BMI (p < 0.01), T stage (p < 0.01), venous invasion (p < 0.01) and peritoneal involvement (p < 0.01). When NPS (myeloid) and mGPS (liver) were directly compared, their relationship with CSS and OS was similar. CONCLUSIONS: Both composite ratios and cumulative scores had prognostic value, independent of TNM stage, in patients with colon cancer. However, cumulative scores, based on normal reference ranges, are simpler and more consistent for clinical use.

A Postoperative Systemic Inflammation Score Predicts Short- and Long-Term Outcomes in Patients Undergoing Surgery for Colorectal Cancer.

BACKGROUND: Following surgery, a significant proportion of patients develop postoperative complications that are associated with poorer long-term survival. Stereotypical markers of the systemic inflammatory response (SIR) have been shown to identify patients at increased risk of developing such complications. The aim of the present study was to examine the prognostic value of a postoperative systemic inflammation-based score in patients undergoing potentially curative surgery for colorectal cancer. METHODS: Patients with histologically proven colorectal cancer undergoing resection between 1999 and 2013 (n = 813) were grouped into two cohorts-a retrospective test cohort (n = 402) and a prospective validation cohort (n = 411). Patients were assessed for postoperative complications and had routine blood samples taken daily. The relationship between markers of the postoperative SIR and survival was examined using Cox regression analysis. RESULTS: In the test cohort, 87 patients developed an infective complication, while in the validation cohort, 106 patients developed an infective complication. In both cohorts, the postoperative SIR (C-reactive protein and albumin thresholds of >150 mg/L and <25 g/L, respectively) were associated with the development of infective complications (all p < 0.01). Using these thresholds, a scoring system [postoperative Glasgow prognostic score (poGPS)] was created, and on days 3 and 4 was associated with an incremental increase in the infective complication rate (all p < 0.001) and complication severity (p < 0.001). In the overall cohort, there were 175 cancer and 139 non-cancer deaths. The poGPS was also significantly associated with overall survival (p < 0.05). CONCLUSIONS: The postoperative SIR, evidenced by the poGPS, was associated with increased complication rates and severity and a reduction in survival.

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.

Colorectal Cancer, Systemic Inflammation, and Outcome: Staging the Tumor and Staging the Host.

OBJECTIVE: This study aims to examine the clinical utility of the combination of TNM stage and modified Glasgow Prognostic Score (mGPS) in patients undergoing potentially curative resection of colorectal cancer (CRC). BACKGROUND: Of measures of the systemic inflammatory response, the mGPS has been most extensively validated in patients with cancer. METHODS: Data from 1000 consecutive patients undergoing potentially curative CRC resection from a single institution (January 1997-May 2013) were included. The relationship between mGPS [0-C-reactive protein (CRP) ≤ 10 mg/L, 1-CRP > 10 mg/L and albumin ≥35 g/L, 2-CRP > 10 mg/L and albumin < 35 g/L], TNM stage, and cancer-specific survival (CSS) and overall survival (OS) was examined using Kaplan-Meier log-rank survival analysis and multivariate Cox regression analysis. RESULTS: An mGPS of 0, 1, and 2 was observed in 63%, 21%, and 16% of patients, respectively. Median follow-up was 56 months (interquartile range: 28-107 months). TNM and mGPS were independently associated with CSS and OS (all P < 0.001). In all patients, TNM and mGPS stratified 5-year CSS and OS from 97% and 87% (stage I, mGPS = 0) to 32% and 26% (stage III, mGPS = 2), respectively. In patients undergoing elective resection of colon cancer (n = 575), 5-year CSS and OS ranged from 100% and 87% (stage I, mGPS = 0) to 37% and 30% (stage III, mGPS = 2), respectively. CONCLUSIONS: This study shows how the combination of TNM and mGPS effectively stratifies outcome in patients undergoing potentially curative resection of CRC. These data support routine staging of both the tumor and the host in patients with CRC.

Postoperative Systemic Inflammatory Response, Complication Severity, and Survival Following Surgery for Colorectal Cancer.

BACKGROUND: This study examined the relationship between the magnitude of the postoperative systemic inflammatory response (SIR), the severity of complications, and long-term outcomes following surgery for colorectal cancer. METHODS: Data were recorded prospectively for patients undergoing potentially curative surgery for colorectal cancer in a single centre between 2008 and 2013. The magnitude of the SIR was measured using C-reactive protein (CRP). Complications were classified by Clavien-Dindo grade. The impact on disease specific and overall survival was assessed using univariate and multivariate Cox regression. RESULTS: Of 377 patients included, the majority were male (55 %), older than age 65 years (68 %), with colonic (63 %) and node-negative disease (66 %). A total of 138 patients (37 %) had a complication, of which 26 (6 %) were Clavien-Dindo grade 3 or 4 severity. Complication severity was significantly associated with the established CRP thresholds of 150 mg/L on postoperative day (POD) 3 (p < 0.001) and POD 4 (p < 0.001). Median follow-up was 42 months with disease-specific survival 86 % and overall survival 78 %. On univariate analysis, complication severity [hazard ratio (HR) 1.66, 95 % confidence interval (CI) 1.13-2.43, p = 0.009], and POD 4 CRP > 150 mg/L (HR 2.53, 95 % CI 1.43-4.48, p = 0.001) were associated with disease-specific survival. On multivariate survival analysis, POD 4 CRP > 150 mg/L (HR 2.00, 95 % CI 1.12-3.59, p = 0.020), but not complication severity, was significantly associated with disease-specific survival independent of TNM stage (HR 2.46, 95 % CI 1.52-4.12, p < 0.001). CONCLUSIONS: The magnitude of the postoperative SIR, evidenced by CRP, was significantly associated with long-term outcomes following surgery for colorectal cancer, independent of complications and stage.

A Survey of Attitudes towards the Clinical Application of Systemic Inflammation Based Prognostic Scores in Cancer.

INTRODUCTION: The systemic inflammatory response (SIR) plays a key role in determining nutritional status and survival of patients with cancer. A number of objective scoring systems have been shown to have prognostic value; however, their application in routine clinical practice is not clear. The aim of the present survey was to examine the range of opinions internationally on the routine use of these scoring systems. METHODS: An online survey was distributed to a target group consisting of individuals worldwide who have reported an interest in systemic inflammation in patients with cancer. RESULTS: Of those invited by the survey (n = 238), 65% routinely measured the SIR, mainly for research and prognostication purposes and clinically for allocation of adjuvant therapy or palliative chemotherapy. 40% reported that they currently used the Glasgow Prognostic Score/modified Glasgow Prognostic Score (GPS/mGPS) and 81% reported that a measure of systemic inflammation should be incorporated into clinical guidelines, such as the definition of cachexia. CONCLUSIONS: The majority of respondents routinely measured the SIR in patients with cancer, mainly using the GPS/mGPS for research and prognostication purposes. The majority reported that a measure of the SIR should be adopted into clinical guidelines.

Meta-analysis of Prolene Hernia System mesh versus Lichtenstein mesh in open inguinal hernia repair.

BACKGROUND: This study was designed to systematically analyse all published randomized clinical trials comparing the Prolene Hernia System (PHS) mesh and Lichtenstein mesh for open inguinal hernia repair. METHOD: A literature search was performed using the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase and Science Citation Index Expanded. Randomized trials comparing the Lichtenstein Mesh repair (LMR) with the Prolene Hernia System were included. Statistical analysis was performed using Review Manager Version 5.1 software. The primary outcome measures were hernia recurrence and chronic pain after operation. Secondary outcome measures included surgical time, peri-operative complications, time to return to work, early and long-term postoperative complications. RESULTS: Six randomized clinical trials were identified as suitable, containing 1313 patients. There was no statistical difference between the two types of repair in operation time, time to return to work, incidence of chronic groin pain, hernia recurrence or long-term complications. The PHS group had a higher rate of peri-operative complications, compared to Lichtenstein mesh repair (risk ratio (RR) 0.71, 95% confidence interval 0.55-0.93, P=0.01). CONCLUSION: The use of PHS mesh was associated with an increased risk of peri-operative complications compared to LMR. Both mesh repair techniques have comparable short- and long-term outcomes.

Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: a systematic review.

BACKGROUND: Operative injury to the body from all procedures causes a stereotypical cascade of neuroendocrine, cytokine, myeloid, and acute phase responses. This response has been examined commonly by the use of cortisol, interleukin-6 (IL-6), white cell count, and C-reactive protein (CRP). We aimed to determine which markers of the systemic inflammatory response were useful in determining the magnitude of injury after elective operations. METHODS: A systematic review of the literature was performed using surgery, endocrine response, systemic inflammatory response, cortisol, IL-6, white cell count, and CRP. For each analyte the studies were grouped according to whether the operative injury was considered to be minor, moderate, or major and then by the operative procedure. RESULTS: A total of 164 studies were included involving 14,362 patients. The IL-6 and CRP responses clearly were associated with the magnitude of operative injury and the invasiveness of the operative procedure. For example, the peak CRP response increased from 52 mg/L with cholecystectomy to 123 mg/L with colorectal cancer resection, 145 mg/L with hip replacement, 163 mg/L after abdominal aortic aneurysm repair, and 189 mg/L after open cardiac surgery. There also appeared to be a difference between minimally invasive/laparoscopic and open procedures such as cholecystectomy (27 vs 80 mg/L), colorectal cancer resection (97 vs 133 mg/L), and aortic aneurysm repair (132 vs 180 mg/L). CONCLUSION: Peak IL-6 and CRP concentrations consistently were associated with the magnitude of operative injury and operative procedure. These markers may be useful in the objective assessment of which components of Enhanced Recovery after Surgery are likely to improve patient outcome and to assess the possible impact of operative injury on immune function.

The Neutrophil-Platelet Score (NPS) Predicts Survival in Primary Operable Colorectal Cancer and a Variety of Common Cancers.

INTRODUCTION: Recent in-vitro studies have suggested that a critical checkpoint early in the inflammatory process involves the interaction between neutrophils and platelets. This confirms the importance of the innate immune system in the elaboration of the systemic inflammatory response. The aim of the present study was to examine whether a combination of the neutrophil and platelet counts were predictive of survival in patients with cancer. METHODS: Patients with histologically proven colorectal cancer who underwent potentially curative resection at a single centre between March 1999 and May 2013 (n = 796) and patients with cancer from the Glasgow Inflammation Outcome Study, who had a blood sample taken between January 2000 and December 2007 (n = 9649) were included in the analysis. RESULTS: In the colorectal cancer cohort, there were 173 cancer and 135 non-cancer deaths. In patients undergoing elective surgery, cancer-specific survival (CSS) at 5 years ranged from 97% in patients with TNM I disease and NPS = 0 to 57% in patients with TNM III disease and NPS = 2 (p = 0.019) and in patients undergoing elective surgery for node-negative colon cancer from 98% (TNM I, NPS = 0) to 65% (TNM II, NPS = 2) (p = 0.004). In those with a variety of common cancers there were 5218 cancer and 929 non-cancer deaths. On multivariate analysis, adjusting for age and sex and stratified by tumour site, incremental increase in the NPS was significantly associated with poorer CSS (p<0.001). CONCLUSION: The neutrophil-platelet score predicted survival in a variety of common cancers and highlights the importance of the innate immune system in patients with cancer.

Enhanced Recovery After Surgery: Which Components, If Any, Impact on The Systemic Inflammatory Response Following Colorectal Surgery?: A Systematic Review.

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.

Neutrophil count is the most important prognostic component of the differential white cell count in patients undergoing elective surgery for colorectal cancer.

BACKGROUND: Systemic inflammatory scoring systems such as the NLR have been reported to have prognostic value in many solid organ cancers. The aim of this study was to examine the relationships between the components of the white cell count (WCC) and survival in patients undergoing elective surgery for colorectal cancer. METHODS: Patients undergoing elective resection at a single center (1997 to 2008) were identified from a prospective database (n = 508). Patient demographics and preoperative laboratory measurements including the differential WCC and their association with cancer-specific survival (CSS) and overall survival were examined. RESULTS: There were 172 cancer deaths and 120 noncancer deaths. On Kaplan-Meier analysis of the whole cohort, age, Tumor, Nodal, and Metastasis stage, venous invasion, margin involvement, peritoneal involvement and tumor perforation, and white cell and neutrophil count (all P < .05) were associated with CSS. In those with node-negative colon cancer (n = 226), on multivariate analysis, age, venous invasion, modified Glasgow Prognostic Score, and neutrophil count (all P < .05) were independently associated with CSS. CONCLUSION: Of the components of a differential WCC, only the neutrophil count was independently associated with survival, particularly in node-negative colon cancer.

Systematic review and meta-analysis of haemostatic and biliostatic efficacy of fibrin sealants in elective liver surgery.

BACKGROUND: Fibrin sealants are frequently used in liver surgery to achieve intraoperative haemostasis and reduce post-operative haemorrhage and bile leak. This meta-analysis aimed to review the haemostatic and biliostatic capacity of fibrin sealants in elective liver surgery. METHODS: An electronic search was performed on the MEDLINE, Embase and PubMed databases using both subject headings and truncated word searches to identify all published articles that are related to this topic. Pooled risk ratios were calculated for categorical outcomes, and mean differences for secondary continuous outcomes, using the fixed-effects and random-effects models for meta-analysis. RESULTS: Ten randomised controlled trials encompassing 1,225 patients were analysed to achieve a summated outcome. Pooled data analysis showed the use of fibrin sealants resulted in reduced time to haemostasis (mean difference -3.45 min [-3.78, -3.13] (P < 0.00001)) and increased numbers of patients with complete haemostasis (risk ratio 1.56, 95 % confidence interval 1.04-2.34, p = 0.03) when compared to controls. The use of fibrin sealants did not influence perioperative blood transfusion requirements, bile leak rates, post-operative haemorrhage, intra-abdominal collections and overall morbidity and mortality compared with controls. CONCLUSIONS: There is no solid evidence that the routine use of fibrin sealants reduces the incidence of post-operative haemorrhage or bile leak compared with other treatments. The use of fibrin sealants may reduce the time to haemostasis, but this does not translate to improved perioperative outcomes.