CT-derived body composition: Differential association with disease, age and inflammation in a retrospective cohort study.

BACKGROUND: Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients. METHODS: Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG). RESULTS: 1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38-1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09-1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66-2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55-7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08-1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03-1.37, p = 0.02) were independently associated with increased odds of low SMD. CONCLUSIONS: Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease.

The Relationship between Liver Volume, Clinicopathological Characteristics and Survival in Patients Undergoing Resection with Curative Intent for Non-Metastatic Colonic Cancer.

INTRODUCTION: The prognostic value of CT-derived liver volume in terms of cancer outcomes is not clear. The aim of the present study was to examine the relationship between liver area on a single axial CT-slice and the total liver volume in patients with colonic cancer. Furthermore, we examine the relationship between liver volume, determined using this novel method, clinicopathological variables and survival. METHODS: Consecutive patients who underwent potentially curative surgery for colonic cancer were identified from a prospectively maintained database. Maximal liver area on axial CT-slice (cm2) and total volume (cm3), were obtained by the manual segmentation of pre-operative CT-images in a PACS viewer. The maximal liver area was normalized for body height2 to create the liver index (LI) and values, categorized into tertiles. The primary outcome of interest was overall survival (OS). Relationships between LI and clinico-pathological variables were examined using chi-square analysis and binary logistic regression. The relationship between LI and OS was examined using cox proportional hazard regression. RESULTS: A total of 359 patients were included. A total of 51% (n = 182) of patients were male and 73% (n = 261) were aged 65 years or older. 81% (n = 305) of patients were alive 3-years post-operatively. The median maximal liver area on the axial CT slice was 178.7 (163.7-198.4) cm2. The median total liver volume was 1509.13 (857.8-3337.1) cm3. Maximal liver area strongly correlated with total liver volume (R2 = 0.749). The median LI was 66.8 (62.0-71.6) cm2/m2. On multivariate analysis, age (p < 0.001), sex (p < 0.05), BMI (p < 0.001) and T2DM (p < 0.05) remained significantly associated with LI. On univariate analysis, neither LI (continuous) or LI (tertiles) were significantly associated with OS (p = 0.582 and p = 0.290, respectively). CONCLUSIONS: The simple, reliable method proposed in this study for quantifying liver volume using CT-imaging was found to have an excellent correlation between observers and provided results consistent with the contemporary literature. This method may facilitate the further examination of liver volume in future cancer studies.

Adverse Tumour and Host Biology May Explain the Poorer Outcomes Seen in Emergency Presentations of Colon Cancer.

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.

The relationship between the mode of presentation, CT-derived body composition, systemic inflammatory grade and survival in colon cancer.

BACKGROUND: Within colorectal cancer, the systemic inflammatory response (SIR) and CT-derived body composition, particularly the loss of lean muscle mass, are independently associated with oncological outcomes; however, no study has included both non-metastatic and metastatic disease. The present study analyses the association between body composition, mode of presentation, SIR and survival in patients with TNM I-IV colon cancer. METHODS: Patients diagnosed with colon cancer from 2011 to 2014 were identified. The SIR was stratified using systemic inflammatory grade (SIG). Staging CT scans were used to define body composition: subcutaneous fat index (SFI), visceral fat area (VFA), skeletal muscle index (SMI) and skeletal muscle density (SMD). The effect of SIG and body composition on mode of presentation and 3-year overall survival (3-yr OS) was analysed. RESULTS: One thousand one hundred forty-six patients were identified; 14%/38%/40%/8% had TNM Stage I/II/III/IV colon cancer, respectively. Patients were predominantly aged 65 + (63%), male (52%) and BMI > 25 (62%). 79%74% had a high SFI/VFA, and 56%/62% had a low SMI/SMD, respectively. Abnormal body composition was prevalent across all disease stages and associated with TNM stage-high SFI in 87%/76%/81%/68% (P < 0.001), high VFA in 79%/73%/75%/67% (P = 0.189), low SMI in 43%/60%/55%/68% (P < 0.001) and low SMD in 55%/65%/61%/67% (P = 0.094) of TNM I/II/III/IV disease, respectively. Body composition was associated with SIG-high SFI in 83%/80%/77%/78%/66% (P = 0.004), high VFA in 78%/78%/70%/63%/61% (P = 0.002), low SMI in 48%/52%/62%/62%/79% (P < 0.001) and low SMD in 56%/60%/62%/70%/76% (P < 0.001) of patients with SIG 0/1/2/3/4, respectively. After adjustment for other factors, increased SIG (OR 1.95), visceral obesity (OR 0.65) and low SMI (OR 1.61) were associated with emergency presentation. In TNM Stage II colon cancer, low SMI and low SMD were associated with worse 3-yr OS (92% vs 87%, P < 0.001 and 96% vs 85%, P < 0.001, respectively). In TNM Stage III, a trend was seen between low SMI and SMD and 3-yr OS (77% vs 73%, P = 0.091 and 76% vs 75%, P = 0.034, respectively). In TNM Stage IV disease, low SMI was associated with 3-yr OS (43% vs 16%, P < 0.001). A trend, albeit not of significance, was seen between low SMD and 3-yr OS (32% vs 21%, P = 0.366). CONCLUSIONS: The present results show that abnormal body composition is prevalent across TNM I-IV colon cancer and associated with TNM stage and SIG. Body composition is independently associated with emergency presentation and long-term survival. Further research is required to analyse whether interventions including structured exercise programmes or attenuation of the SIR have an effect on CT-derived body composition and oncological outcomes.

Relationship between pre-operative glycated haemoglobin and surgical site infection in patients undergoing elective colon cancer surgery.

Surgical site infections remain a significant cause of morbidity following colon cancer surgery. Although diabetes has been recognised as a risk factor, patients with asymptomatic diabetes are likely underdiagnosed. The aim of the present study was to determine the relationship between preoperative glycated haemoglobin (HbA1C), clinicopathological characteristics and the influence on surgical site infection in a cohort of patients undergoing potentially curative colon cancer surgery. Patients who underwent elective, potentially curative colon cancer surgery between January 2011 and December 2014 were assessed for HbA1C levels (mmol/mol) measured within 3 months preoperatively. Clinicopathological data were recorded in a maintained database. A multivariate binary logistic regression model was used to assess the relationship between HbA1C, clinicopathological characteristics and surgical site infections. A total of 362 patients had HbA1C levels preoperatively recorded. HbA1C was significantly associated with body mass index (BMI), diabetes, smoking status, visceral fat area and skeletal muscle index. As determined by multivariate analysis, preoperative HbA1C levels remained independently associated with an increased risk of surgical site infections (OR 1.69, 95% CI 1.05-2.7; P=0.031) together with BMI (OR 1.91, 95% CI 1.36-2.67; P<0.001). Notably, in the present study, tumour-based factors, such as tumour location and TNM status, were not associated with infective complications. By contrast, host factors, such as BMI and pre-operative HbA1C were associated with surgical site infections suggesting that these factors were of more importance in determining short-term outcomes. In conclusion, objective measurements of BMI and HbA1C effectively stratified the risk of developing surgical site infection from 8 to 59%; therefore, HbA1C levels should be determined to allow for preoperative optimisation.

Evaluation of clinical prognostic variables on short-term outcome for colorectal cancer surgery: An overview and minimum dataset.

INTRODUCTION: Surgery for colorectal cancer is associated with post-operative morbidity and mortality. Multiple systematic reviews have reported on individual factors affecting short-term outcome following surgical resection. This umbrella review aims to synthesize the available evidence on host and other factors associated with short-term post-operative complications. METHODS: A comprehensive search identified systematic reviews reporting on short-term outcomes following colorectal cancer surgery using PubMed, Cochrane Database of Systematic Reviews and Web of Science from inception to 8th September 2020. All reported clinicopathological variables were extracted from published systematic reviews. RESULTS: The present overview identified multiple validated factors affecting short-term outcomes in patients undergoing colorectal cancer resection. In particular, factors consistently associated with post-operative outcome differed with the type of complication; infective, non-infective or mortality. A minimum dataset was identified for future studies and included pre-operative age, sex, diabetes status, body mass index, body composition (sarcopenia, visceral obesity) and functional status (ASA, frailty). A recommended dataset included antibiotic prophylaxis, iron therapy, blood transfusion, erythropoietin, steroid use, enhance recovery programme and finally potential dataset included measures of the systemic inflammatory response CONCLUSION: A minimum dataset of mandatory, recommended, and potential baseline variables to be included in studies of patients undergoing colorectal cancer resection is proposed. This will maximise the benefit of such study datasets.

Determinants of emergency presentation in patients with colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer remains a significant cause of morbidity and mortality, even despite curative treatment. A significant proportion of patients present emergently and have poorer outcomes compared to elective presentations, independent of TNM stage. In this systematic review and meta-analysis, differences between elective/emergency presentations of colorectal cancer were examined to determine which factors were associated with emergency presentation. A literature search was carried out from 1990 to 2018 comparing elective and emergency presentations of colon and/or rectal cancer. All reported clinicopathological variables were extracted from identified studies. Variables were analysed through either systematic review or, if appropriate, meta-analysis. This study identified multiple differences between elective and emergency presentations of colorectal cancer. On meta-analysis, emergency presentations were associated with more advanced tumour stage, both overall (OR 2.05) and T/N/M/ subclassification (OR 2.56/1.59/1.75), more: lymphovascular invasion (OR 1.76), vascular invasion (OR 1.92), perineural invasion (OR 1.89), and ASA (OR 1.83). Emergencies were more likely to be of ethnic minority (OR 1.58). There are multiple tumour/host factors that differ between elective and emergency presentations of colorectal cancer. Further work is required to determine which of these factors are independently associated with emergency presentation and subsequently which factors have the most significant effect on outcomes.

The prognostic value of combined measures of the systemic inflammatory response in patients with colon cancer: an analysis of 1700 patients.

BACKGROUND: The pre-operative systemic inflammatory response (SIR) measured using an acute-phase-protein-based score (modified Glasgow Prognostic Score (mGPS)) or the differential white cell count (neutrophil-lymphocyte ratio (NLR)) demonstrates prognostic significance following curative resection of colon cancer. We investigate the complementary use of both measures to better stratify outcomes. METHODS: The effect on survival of mGPS and NLR was examined using uni/multivariate analysis (UVA/MVA) in patients undergoing curative surgery for colon cancer. The synergistic effect of these scores in predicting OS/CSS was examined using a Systemic Inflammatory Grade (SIG). RESULTS: One thousand seven hundred and eight patients with TNM-I-III colon cancer were included. On MVA both mGPS and NLR were significant for OS (HR 1.16/1.21, respectively). Three-year survival stratified by mGPS was 83-58%(TNM-I-III), 87-65%(TNM-II) and 75-49%(TNM-III), and by NLR was 84-62%(TNM-I-III), 88-69%(TNM-II) and 77-49%(TNM-III). When mGPS and NLR were combined to form an overall SIG 0/1/2/3/4, this stratified 3-year OS 88%/84%/76%/65%/60% and CSS 93%/90%/82%/73%/70%, respectively (both p < 0.001). SIG stratified OS 93-68%/82-48% and CSS 97-80%/86-58% in TNM Stage II/III disease, respectively (all p < 0.001). CONCLUSIONS: The present study shows that the pre-operative SIR in patients undergoing curative surgery for colon cancer is best measured using a SIG utilising mGPS and NLR.

Aortic calcification is associated with non-infective rather than infective postoperative complications following colorectal cancer resection: an observational cohort study.

OBJECTIVES: Complications following colorectal cancer resection are common. The degree of aortic calcification (AC) on CT has been proposed as a predictor of complications, particularly anastomotic leak. This study assessed the relationship between AC and complications in patients undergoing colorectal cancer resection. METHODS: Patients from 2008 to 2016 were retrospectively identified from a prospectively maintained database. Complications were classified using the Clavien-Dindo (CD) scale. Calcification was quantified on preoperative CT by visual assessment of the number of calcified quadrants in the proximal and distal aorta. Scores were grouped into categories: none, minor (< median AC score) and major (> median AC score). The relationship between clinicopathological characteristics and complications was assessed using logistic regression. RESULTS: Of 657 patients, 52% had proximal AC (> median score (1)) and 75% had distal AC (> median score (4)). AC was more common in older patients and smokers. Higher burden of AC was associated with non-infective complications (proximal AC 28% vs 16%, p = 0.004, distal AC 26% vs 14% p = 0.001) but not infective complications (proximal AC 28% vs 29%, p = 0.821, distal AC 29% vs 23%, p = 0.240) or anastomotic leak (proximal AC 6% vs 4%, p = 0.334, distal AC 7% vs 3%, p = 0.077). Independent predictors of complications included open surgery (OR 1.99, 95%CI 1.43-2.79, p = 0.001), rectal resection (OR 1.51, 95%CI 1.07-2.12, p = 0.018) and smoking (OR 2.56, 95%CI 1.42-4.64, p = 0.002). CONCLUSIONS: These data suggest that high levels of AC are associated with non-infective complications after colorectal cancer surgery and not anastomotic leak. KEY POINTS: • Aortic calcification measured by visual quantification of the number of calcified quadrants at two aortic levels on preoperative CT is associated with clinical outcome following colorectal cancer surgery. • An increased burden of aortic calcification was associated with non-infective complications but not anastomotic leak. • Assessment of the degree of aortic calcification may help identify patients at risk of cardiorespiratory complications, improve preoperative risk stratification and assign preoperative strategies to improve fitness for surgery.

Attitudes towards the use of perioperative steroids in resectional colorectal cancer surgery in the UK: A qualitative study.

INTRODUCTION: Resectional surgery remains the mainstay of treatment for colorectal cancer. A heightened postoperative systemic inflammatory response has been shown to correlate negatively with short/long-term outcomes. Perioperative steroid administration may help to alleviate this systemic inflammatory response. This survey has been carried out to assess current attitudes towards perioperative steroid use and to gauge interest in a randomised control trial in this area. METHOD: An internet-based survey consisting of 9 questions was circulated via email. Those responses from outside the United Kingdom were excluded. RESULT: 74 doctors from the United Kingdom, predominantly Consultant Anaesthetists (54%) responded to this survey. 77% gave some or all of their patients steroids, in 75% of cases at the discretion of the anaesthetist. The main perceived benefit was to reduce postoperative nausea and vomiting. Diabetics and those deemed at high risk of wound infection were the group in whom most respondents would be reluctant to give steroids. 32% of respondents had no concerns. 87% of respondents felt that a randomised trial in this field would be of clinical interest with most respondents (58%) preferring a three-armed trial - no steroids vs low dose steroids vs high dose steroids. CONCLUSION: This survey indicated that perioperative steroid use is currently widespread. Sufficient equipoise exists for a trial in this area with regard to examining the impact of dexamethasone on postoperative complications and the postoperative systemic inflammatory response. Respondents favoured a 3-armed trial - no steroids vs low-dose steroids vs high-dose steroids.