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.

Postoperative C-reactive protein measurement predicts the severity of complications following surgery for colorectal cancer.

PURPOSE: Studies have shown that postoperative serum C-reactive protein (CRP) measurement may be useful in predicting the type of complication, infective or otherwise, following surgery for colorectal cancer. It may be that the magnitude of the postoperative CRP is also associated with the severity of the complication. The aim of the present study was to examine the relationship between daily postoperative CRP concentrations and Clavien-Dindo complication grade. PATIENTS AND METHODS: Data was recorded prospectively for patients undergoing elective, potentially curative, surgery for colorectal cancer in two hospitals between January 2011 and January 2013, n = 241. All patients had daily CRP measurement following surgery for the first four postoperative days. Complications were retrospectively classified by Clavien-Dindo grade. RESULTS: Of the 241 patients, the majority were male (59%) and were over 65 years old (69%). The majority had colonic (86%) and node negative (65%) disease. One hundred nineteen patients (49%) developed a complication, and 28 (12%) of these were Clavien-Dindo grade 3, 4 or 5. Median and established threshold CRP concentrations on postoperative days 2 (>190 mg/L), 3 (>170 mg/L) and 4 (>125 mg/L) were directly associated with an increase in the Clavien-Dindo grade (all p < 0.001). CONCLUSION: There was a direct association between exceeding established postoperative day 2, 3 and 4 CRP thresholds and the severity of complications defined by the Clavien-Dindo grade.

The impact of open versus laparoscopic resection for colon cancer on C-reactive protein concentrations as a predictor of postoperative infective complications.

BACKGROUND: There is increasing evidence that C-reactive protein is a useful negative predictor of infective complications and anastomotic leak following surgery for colorectal cancer. In particular, C-reactive protein concentrations on postoperative days 3 and 4 have been proposed to be of clinical utility since they aid safe and early discharge of selected patients following colorectal surgery. However, it is not clear whether such thresholds are also applicable in laparoscopic surgery. The aim of the present study was to compare the value of daily C-reactive protein concentrations in the prediction of postoperative infective complications in patients undergoing open versus laparoscopic resection for colon cancer. METHODS: Patients with histologically proven colon cancer who were considered to have undergone potentially curative resection in one of two university teaching hospitals in Glasgow were included in the study (n = 344). Patient characteristics were collected in a prospective surgical database. All resections were elective cases and were performed using either open (n = 191) or laparoscopic surgery (n = 153). Daily blood samples to measure C-reactive protein concentrations perioperatively were taken routinely. Patients were assessed for postoperative infective and non-infective complications. RESULTS: The majority of patients were aged 65 years or older (75%), male (52%), had left-sided tumors (54%), node negative disease (77%), and did not undergo neoadjuvant treatment (94%). Patients undergoing open and laparoscopic resection were similar in terms of age, sex, tumor site, TNM stage, comorbidity, and infective complications. In contrast, preoperative and postoperative days 1-3 C-reactive protein concentrations were lower following laparoscopic compared with open resection in the whole cohort (n = 344; all p < 0.001) and in those who did not develop infective complications (n = 251; all p < 0.001). The median length of hospital stay was shorter in the laparoscopic resection (p < 0.001). During follow-up, 127 (37%) patients developed a postoperative complication, 93 (73%) of which were infective complications. In those who developed an infective complication, there was no significant difference in the C-reactive protein concentrations between open and laparoscopic resections on postoperative days 1-4. C-reactive protein thresholds predictive of infective complications were the same on postoperative days 3 (180 mg/l) and 4 (140 mg/l) following both open and laparoscopic resection for colon cancer. CONCLUSIONS: The results of the present study show that although the magnitude of the systemic inflammatory response, as evidenced by C-reactive protein, following surgery was greater in open compared with laparoscopic resection, the threshold concentrations of C-reactive protein for the development of postoperative infective complications were remarkably similar on days 3 and 4.

Impact of day 2 C-reactive protein on day 3 and 4 thresholds associated with infective complications following curative surgery for colorectal cancer.

BACKGROUND: The postoperative systemic inflammatory response, as evidenced by C-reactive protein (CRP) on days 3 and 4, has been reported to be associated with the development of infective complications following surgery for colorectal cancer. However, patients in enhanced recovery after surgery require earlier assessment at day 2, the peak CRP response to surgery. The aim of the present study was to assess the impact of day 2 CRP on the CRP concentrations on days 3 and 4. METHODS: Patients with colorectal cancer undergoing elective resection were recorded in a prospective database (n = 357). CRP was measured preoperatively and on days 1-4 postoperatively. Correlations between day 2 CRP and day 3 and day 4 CRP concentrations were examined. RESULTS: The majority of patients were ≥ 65 (72 %), male (53 %), underwent right or left hemicolectomy (63 %), and had node-negative disease (61 %). Day 2 CRP was not significantly associated with age, sex, operation type, or tumor stage. Day 2 CRP was directly associated with day 3 (r (2) = 0.601, p < 0.001) and day 4 (r (2) = 0.270, p < 0.001) CRP. The median day 2 CRP that corresponded with the previously described thresholds for predicting infective complications was ~190 mg/L, and for predicting an anastomotic leak 200 mg/L. CONCLUSIONS: A day 2 CRP concentration >190 mg/L was associated with day 3 and 4 CRP concentrations above established CRP thresholds for the development of infective complications.

Is perioperative systemic inflammation the result of insufficient cortisol production in patients with colorectal cancer?

BACKGROUND: Patients with colorectal cancer who have a raised systemic inflammatory response before surgery have been shown to have poorer long-term and short-term outcomes. The presence of an ongoing systemic inflammatory response in these patients may be due to impaired cortisol production. The aim of the present study was to examine the relationship between the perioperative systemic inflammatory response and endogenous cortisol production. METHODS: A prospective study was performed to incorporate the assessment of adrenocortical function using synthetic adrenocorticotrophic hormone, a short Synacthen test, as part of the preoperative assessment of patients undergoing resection for colorectal cancer. RESULTS: A total of 80 patients underwent short Synacthen testing. There were no significant associations between the baseline, 30 min, or change (both relative and absolute) in cortisol and age (all p > 0.10), sex (all p > 0.10), site (all p > 0.10), TNM stage (all p > 0.10), modified Glasgow prognostic score (all p > 0.10), NLR (all p > 0.10), white cell count (all p > 0.10) or postoperative C-reactive protein concentrations (all p > 0.10). CONCLUSIONS: Impaired cortisol production was uncommon in patients with potentially curable colorectal cancer. The presence of a perioperative systemic inflammatory response was not significantly associated with impaired cortisol production.

C-reactive protein as a predictor of postoperative infective complications after curative resection in patients with colorectal cancer.

BACKGROUND: Infective complications particularly in the form of surgical site infections including anastomotic leak represent a serious morbidity after colorectal cancer surgery. Systemic inflammation markers, including C-reactive protein (CRP) and white cell count, have been reported to provide early detection. However, their relative predictive value is unclear. The aim of the present study was to examine the diagnostic accuracy of serial postoperative WCC, albumin and CRP in detecting infective complications. METHODS: White cell count, albumin and CRP were measured postoperatively for 7 days in 454 consecutive patients undergoing surgery for colorectal cancer. All postoperative complications were recorded. The diagnostic accuracy of the white cell count, albumin and CRP values were analyzed by receiver operating characteristics curve analysis with surgical site infective complications as outcome measures. RESULTS: One hundred four patients (23 %) developed infective complications, and 26 of them developed an anastomotic leak. CRP was most sensitive to the development of an infective complication, surgical site or at a remote site. On postoperative day 3 CRP the area under the receiver operating characteristic curve was 0.80 (p < 0.001) and the optimal cutoff value was 170 mg/L. This threshold was also associated with an increase in the length of hospital stay (p < 0.001), 30 day mortality (p < 0.05) and 12 month mortality (p < 0.10). CONCLUSIONS: Postoperative CRP measurement on day 3 postoperatively is clinically useful in predicting surgical site infective complications, including an anastomotic leak, in patients undergoing surgery for colorectal cancer.