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Objective: To examine the association between tumor/host factors (including the systemic inflammatory response), mode of presentation, and short/long-term outcomes in patients undergoing curative resectional surgery for TNM I to III colon cancer., Background: Emergency presentations of colon cancer are associated with worse long-term outcomes than elective presentations despite adjustment for TNM stage. A number of differences in tumor and host factors have been identified between elective and emergency presentations and it may be these factors that are associated with adverse outcomes., Methods: Patients undergoing curative surgery for TNM I to III colon cancer in the West of Scotland from 2011 to 2014 were identified. Tumor/host factors independently associated with the emergency presentation were identified and entered into a subsequent survival model to determine those that were independently associated with overall survival/cancer-specific survival (OS/CSS)., Results: A total of 2705 patients were identified. The emergency presentation was associated with a worse 3-year OS and CSS compared with elective presentations (70% vs 86% and 91% vs 75%). T stage, age, systemic inflammatory grade, anemia (all P < 0.001), N stage ( P = 0.077), extramural venous invasion ( P = 0.003), body mass index ( P = 0.001), and American Society of Anesthesiologists Classification classification ( P = 0.021) were independently associated with emergency presentation. Of these, body mass index [hazard ratio (HR), 0.82], American Society of Anesthesiologists Classification (HR, 1.45), anemia (HR, 1.29), systemic inflammatory grade (HR. 1.11), T stage (HR, 1.57), N stage (HR, 1.80), and adjuvant chemotherapy (HR, 0.47) were independently associated with OS. Similar results were observed for CSS., Conclusions: Within patients undergoing curative surgery for colon cancer, the emergency presentation was not independently associated with worse OS/CSS. Rather, a combination of tumor and host factors account for the worse outcomes observed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients., Method: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts., Results: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients., Conclusion: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.

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.

Objective: To examine the clinical utility of improved detection of venous invasion (VI) in patients undergoing potentially curative resection of colorectal cancer., Background: VI is a feature of colorectal cancer (CRC) progression. Elastica staining can be used to improve detection of VI and correspondingly its prediction of patient survival., Methods: A single-center, observational study of pathology variables, including detection of VI by staining for elastica, using 631 stage I to III CRC specimens, collected from 1997 to 2009 (176 analyzed retrospectively and 455 analyzed prospectively), was performed., Results: VI was detected in 56% of patients with CRC. Over a median follow-up period of 73 months, 238 patients died (134 from cancer). On multivariate analysis, VI by elastica staining was associated with a shorter survival duration, independent of other pathology features, in all cases [hazard ratio (HR) = 3.94, 95% confidence interval (CI): 2.33-6.65, P < 0.001] and in node-negative cases (HR = 3.55, 95% CI: 1.81-6.97; P < 0.001). In the absence of elastica-detected VI, with the exception of T stage, no other pathology features were associated with survival time. Therefore, the combination of T stage and VI (TVI) on survival was examined. Five-year cancer mortality could be stratified between 100% and 54% for patients with node-negative tumors and between 100% and 33% for patients with node-positive tumors. In all cases, the TVI had similar predictive value as that of T stage and node status (TNM). In node-negative disease, TVI had superior predictive value., Conclusions: The results of the present study have prompted the development of a novel tumor staging system based on TVI. The TVI has clinical utility, especially in node-negative disease, in predicting outcome following curative resection for CRC.

Objective: The objective of the study was to identify determinants of disease recurrence after potentially curative resection of colorectal cancer., Summary Background Data: The identification of patients at increased risk of disease recurrence is currently based on pathological factors. Recently, there has been considerable interest in the potential impact of perioperative factors on long-term colorectal cancer outcome. Few studies have examined pre-, intra-, and postoperative variables in a single cohort., Methods: Four hundred and twenty-three patients with histologically confirmed colorectal cancer who underwent surgery with curative intent between 1997 and 2007 were included. Pre-, intra-, and postoperative variables were recorded. Logistic and Cox regression analyses were performed to identify predictors of surgical complications and disease recurrence, respectively., Results: The postoperative mortality rate was 4% and the morbidity rate 34%. The most important predictors of complications were smoking (odd ratio [OR] 1.32), ASA grade (OR 1.90) and POSSUM operative score (OR 1.32). During follow up (median 80 months), 35% of patients developed disease recurrence. Predictors of recurrence, independent of tumor stage, were POSSUM physiology score (hazard ratio [HR] 1.31) and systemic inflammatory response (HR 1.31)., Conclusions: Preoperative risk factors, but not postoperative complications, are associated with early disease recurrence after potentially curative resection of colorectal cancer.

Objective: To examine the prognostic implications of routine elastica staining for venous invasion on prediction of cancer-specific survival in colorectal cancer., Summary Background Data: Venous invasion is an important high risk feature in colorectal cancer, although prevalence in published studies ranges from 10% to 90%. To resolve the disparity, elastica stains have been used in our institution to provide a more objective judgment since 2002., Methods: The study included 419 patients undergoing curative elective colorectal cancer resection between 1997 and 2006. Patients were grouped prior to (1997-2001 [cohort 1]) and following the introduction of elastica staining (2003-2006 [cohort 2])., Findings: Clinicopathologic characteristics and 3-year survival rates were similar in both groups. Rate of detected venous invasion increased from 18% to 58% following introduction of elastica staining (P < 0.001). The 3-year cancer-specific survival rate associated with the absence of venous invasion was 84% in cohort 1, compared with 96% in cohort 2 (P < 0.01). Elastica staining improved the prognostic value of venous invasion, showing the area under the receiver operator curve rising from 0.59 (P = 0.040; 1997-2001) to 0.68 (P < 0.001; 2003-2006), using cancer mortality as an end point. A direct comparison between H&E alone and elastica Hematoxylin and Eosin (H&E) was made in 53 patients. The area under the receiver operator curve increased from 0.58, P = 0.293 (H&E alone) to 0.74, P = 0.003 for venous invasion detected using the elastica method., Conclusions: Increased detection of venous invasion with elastica staining, compared with H&E staining, provides superior prediction of cancer survival in colorectal cancer. This relationship was seen in the comparison of 2 consecutive cohorts and in a direct comparison in a single cohort. Based on these results, elastica staining should be incorporated into the routine pathologic assessment of venous invasion in colorectal cancer.

Objective: To examine interrelationships between the local inflammatory response (Klintrup and Jass scores) and the systemic inflammatory response (Glasgow prognostic score [GPS]), and compare their prognostic value in patients undergoing curative resection for colorectal cancer., Background: Both localized peritumoral inflammatory cell infiltrate and the host systemic inflammatory response are known to have prognostic value in colorectal cancer. However, the interrelationships of biochemical and cellular components of the systemic inflammatory response and the local inflammatory response are poorly understood., Methods: Retrospective study of 287 patients who underwent surgery between 1997 and 2004. Data were collected from routine preoperative blood tests. Routine pathology specimens were scored according to Jass and Klintrup criteria for peritumoral infiltrate., Results: Increased Dukes stage was associated with less peritumoral infiltrate (Jass criteria: P < 0.001, Klintrup criteria: P < 0.01). Increased modified GPS (mGPS) was associated with increased circulating white cell (P < 0.01) and neutrophil (P < 0.01) counts and low lymphocyte counts (P < 0.01). Increased circulating white cell count was associated with increased neutrophil count (P < 0.001) and low-grade peritumoral infiltrate (P < 0.05, Klintrup criteria). Jass and Klintrup criteria for peritumoral infiltrate were directly associated (P < 0.001). On univariate survival analysis of patients with node-negative disease (Dukes A and B), age (P < 0.01), mGPS (P < 0.01), neutrophil count (P < 0.05), and Klintrup criteria (P < 0.05) were associated with cancer-specific survival. On multivariate survival analysis in node-negative disease, the mGPS (hazard ratio: 2.61, 95% CI: 1.27-5.35, P < 0.01) and Klintrup criteria (hazard ratio: 6.31, 95% CI: 1.40-28.44, P < 0.05) were independently associated with cancer-specific survival., Conclusions: The results of the present study suggest low peritumoral infiltrate (Klintrup criteria) and increased systemic inflammation (mGPS criteria) are linked through the cell-mediated immune system. Furthermore, both pathologic (Klintrup) and biochemical (mGPS) measures of the inflammatory response predict survival after colorectal cancer surgery.

Objective: To determine whether suppression of albumin synthesis contributes to the hypoalbuminemia observed in weight-losing cancer patients with evidence of an ongoing acute-phase protein response (APPR)., Background Data: Proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are known to downregulate albumin synthesis and increase acute-phase protein production in isolated hepatocytes. However, whether albumin synthesis is suppressed in hypoalbuminemic cancer patients with evidence of an ongoing acute-phase response is unknown., Methods: Albumin synthesis rates were determined in six healthy controls and in six weight-losing pancreatic cancer patients with an ongoing APPR using a flooding dose technique with [2H5]-phenylalanine. The presence of an APPR was defined as a serum C-reactive protein concentration >10 mg/L. Serum cytokines (TNF, IL-6) and soluble TNF receptors (sTNF-R 55 and 75), along with serum cortisol and insulin, were also measured in both groups., Results: Cancer patients had reduced serum albumin (median 32 [range, 23-36] vs. 42 g/L [40-45]; p < 0.01) and increased serum C-reactive protein concentrations (72 [23-126] vs. <5 mg/L; p < 0.01) when compared with controls. TNF was not detected in either group. sTNF-R 55 levels were significantly elevated in the cancer patients (3.8 [1.9-8.1] vs. 1.2 pg/mL [0.9-2.2]; p < 0.01). Circulating IL-6, insulin, and cortisol concentrations were not significantly different between the groups. The intravascular albumin mass was lower (88 [56-93] vs. 133 g [105-177]; p < 0.01), but the intravascular albumin fractional synthetic rate was higher (13.9 [13.5-18.5] vs. 10.3%/d [71-11.3]; p < 0.01) in the cancer patients compared with the controls. The total intravascular albumin synthetic rate was, however, similar between the two groups (12.7 [7.7-15.7] vs. 11.7 g/d [8.5-18.7]; p NS)., Conclusions: In weight-losing pancreatic cancer patients with evidence of an ongoing APPR, hypoalbuminemia is not caused by a decreased rate of albumin synthesis.

It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation.