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Colorectal cancer progression and survival is dependent on complex interactions between the tumour and the host. The pronounced local inflammatory response in and around the tumour is thought to represent the in situ host anti-tumour immune response. Since early reports, 40years ago, there has been a continuing interest in establishing the cellular composition of immune cell infiltrates and their relationship with survival in colorectal cancer. In this review, we comprehensively examine the evidence for the local inflammatory cell reaction/in situ immune response in predicting outcome in primary operable colorectal cancer and make recommendations as to how such information may be incorporated into routine clinical assessment. Generally, an increasing number/density of immune cells in and around the tumour is associated with improved outcome in over 100 studies. Whilst the prognostic value of a generalized lymphocytic infiltrate or non-specific peritumoural inflammatory response is strongly related to survival based on 40 different studies, it is also apparent that most individual immune cell types relate to recurrence and cancer specific survival. The evidence is particularly robust for tumour infiltrating T lymphocytes and their subsets (CD3+, CD8+, CD45RO+, FOXP3+) in addition to tumour associated macrophages, dendritic cells and neutrophils. Taken together, the evidence suggests both adaptive and innate anti-tumour immune responses play key roles in determining cancer progression. In order to establish routine clinical utility there is a need to rationalise this prognostic information, published over a 40years period, into a standardized assessment of tumour inflammatory cell infiltrate. Such standardization may also guide development of novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: The host inflammatory response is an important determinant of cancer outcome. We examined different methods of assessing the local inflammatory response in colorectal tumours and explored relationships with both clinicopathological characteristics and survival.Methods: Cohort study of patients (n=130) with primary operable colorectal cancer and mature follow-up. Local inflammatory response at the invasive margin was assessed with: (1) a semi-quantitative assessment of peritumoural inflammation using Klintrup-Makinen (K-M) grading and (2) an assessment of individual immune cell infiltration (lymphocytes, plasma cells, neutrophils, macrophages and eosinophils).Results: The peritumoural inflammatory response was K-M low grade in 48% and high grade in 52%. Inflammatory cells were primarily macrophages, lymphocytes and neutrophils with relatively few plasma cells or eosinophils. On univariate analysis, K-M grade, lymphocyte infiltration and plasma cell infiltration were associated with cancer-specific survival. On multivariate analysis, only systemic inflammatory response, TNM (tumour, node and metastases) stage, venous invasion, tumour necrosis and K-M grade were independently associated with cancer-specific survival. There was no relationship between local infiltration of inflammatory cells and a systemic inflammatory response. However, high K-M grade, lymphocyte infiltration and plasma cell infiltration were associated with a number of favourable pathological characteristics, including an absence of venous invasion.Conclusion: Infiltration of inflammatory cells in the invasive margin of colorectal tumours is beneficial to survival. The adaptive immune response appears to have a prominent role in the prevention of tumour progression in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemistry of Ki-67 protein is widely used to assess tumour proliferation, and is an established prognostic factor in breast cancer. There is interest in automating the assessment of Ki-67 labelling index (LI) with possible benefits in handling increased workload, with improved accuracy and precision.Patients and Methods: Visual and automated assessment of Ki-67 LI and survival were examined in patients with primary operable invasive ductal breast cancer. Tissue microarrays (n=379 patients) immunostained for Ki-67 were scored visually and automatically with the Slidepath Tissue IA system.Results: Visual and automated Ki-67 LI were in excellent agreement (ICCC=0.96, P<0.001). On univariate analysis, visual (P<0.001) and automated Ki67 LI (P<0.05) were associated with cancer-specific survival in patients with invasive ductal breast cancer overall and in patients who received endocrine therapy (Tamoxifen) (P<0.01 for visual and P<0.05 for automated scoring).Conclusion: Automated assessment of Ki-67 LI would appear to be comparable to visual Ki-67 LI. However, automated Ki-67 LI assessment was inferior in predicting cancer survival in patients with breast cancer, including patients who received Tamoxifen. [ABSTRACT FROM AUTHOR]

Background: Trichloroethylene (TCE) is a suspected human carcinogen and a common groundwater contaminant. Chloral hydrate (CH) is the major metabolite of TCE formed in the liver by cytochrome P450 2E1. CH is metabolized to the hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH) and to the noncarcinogenic metabolite trichloroethanol (TCOH) by alcohol dehydrogenase (ADH) . ALDH and ADH are polymorphic in humans, and these polymorphisms are known to affect the elimination of ethanol. It is therefore possible that polymorphisms in CH metabolism will yield subpopulations with greater than expected TCA formation with associated enhanced risk of liver tumors after TCE exposure. Methods: The present studies were undertaken to determine the feasibility of using commercially available, cryogenically preserved human hepatocytes to determine simultaneously the kinetics of CH metabolism and ALDH/ADH genotype. Thirteen human hepatocyte samples were examined. Linear reciprocal plots were obtained for 11 ADH and 12 ALDH determinations. Results: There was large interindividual variation in the V(subscript)max(/subscript) values for both TCOH and TCA formation. Within this limited sample size, no correlation with ADH/ALDH genotype was apparent. Despite the large variation in V(subscript)max(/subscript) values among individuals, disposition of CH into the two competing pathways was relatively constant. Conclusions: These data support the use of cryopreserved human hepatocytes as an experimental system to generate metabolic and genomic information for incorporation into TCE cancer risk assessment models. The data are discussed with regard to cellular factors, other than genotype, that may contribute to the observed variability in metabolism of CH in human liver. [ABSTRACT FROM AUTHOR]

BACKGROUND: The factors contributing to the high mortality after emergency abdominal surgery are unclear. Recent studies have revealed gender differences in immune function after trauma and in the presence of sepsis. OBJECTIVE: This study tested the hypothesis that factors determining survival after emergency abdominal surgery differ in males and females. METHODS: Consecutive patients, aged > or =50 years, who underwent emergency abdominal surgery between July 1998 and June 2000 at the Royal and Western Infirmaries in Glasgow, Scotland, were identified for study. Data collected retrospectively included sex, age, severity of surgery, seniority of surgeon and anesthetist, extent of deprivation, and 30-day postoperative mortality. RESULTS: A total of 633 patients were identified for study; 49 (8%) were excluded from analysis because 30-day mortality or surgery details were unavailable. Of the remaining 584 patients, 256 were male and 328 were female. The overall 30-day mortality was 26%, with 74 (29%) males and 79 (24%) females dying within this period. The mortality rates were 25% in males and 10% in females (P = 0.043) after minor surgery, 26% in males and 23% in females (P = NS) after intermediate surgery, and 44% in males and 39% in females (P = NS) after major surgery. On univariate logistic regression analysis in males, increasing age (P < 0.001), severity of surgery (P = 0.04), and seniority of anesthetist (P < 0.001) were associated with mortality. In females, severity of surgery (P < 0.001) was associated with mortality. CONCLUSIONS: These results show that in females, 30-day mortality was determined by severity of surgery, whereas in males increasing age and seniority of anesthetist also influenced 30-day mortality. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that circulating concentrations of leptin might play a role in cancer cachexia. In the first part of the study, we compared circulating concentrations of free and total leptin, percent fat mass, and the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), together with appetite score, in age- and gender-matched healthy controls (n = 11) and advanced gastrointestinal cancer patients (n = 26). In the second part of the study, the same measurements were repeated before and after megestrol acetate treatment of weight-losing gastrointestinal cancer patients (n = 10). Body mass index and percent fat mass were significantly lower (P < 0.05) and IL-6 and CRP were significantly higher (P < 0.05) in cancer patients than in controls. There was no difference in the percentage of leptin bound in the circulation between controls and cancer patients. Circulating 'free' leptin concentrations correlated with percent fat mass in controls (r = 0.745, P = 0.008) and cancer patients (r = 0.600, P = 0.001). In cancer patients, circulating leptin concentrations, either free or total, were not correlated with IL-6 or CRP concentrations. When adjusted for fat mass, the circulating concentrations of free and total leptin were significantly lower in the cancer patients (P < 0.01). Megestrol acetate treatment significantly increased circulating free and total leptin concentrations in the cancer patients (P < 0.05). There was a significant positive correlation between the change in circulating concentrations of free and total leptin and the change in percent fat mass (r = 0.685, P < 0.05 and r = 0.661, P < 0.05, respectively). The results of the present study indicate that the proportions of free and bound leptin in the circulation do not differ between normal subjects and patients with gastrointestinal cancer and in both groups are related to fat mass. Furthermore, the increase in circulating leptin concentrations after megestrol acetate treatment is not associated with any alteration in leptin binding. [ABSTRACT FROM AUTHOR]

Weight loss in advanced cancer patients is refractory to conventional nutritional support. This may be due to metabolic changes mediated by proinflammatory cytokines, hormones, and tumor-derived products. We previously showed that a nutritional supplement enriched with fish oil will reverse weight loss in patients with pancreatic cancer cachexia. The present study examines the effect of this supplement on a number of mediators thought to play a role in cancer cachexia. Twenty weight-losing patients with pancreatic cancer were asked to consume a nutritional supplement providing 600 kcal and 2 g of eicosapentaenoic acid per day. At baseline and after 3 wk, patients were weighed and samples were collected to measure serum concentrations of interleukin (IL)-6 and its soluble receptor tumor necrosis factor receptors I and II, cortisol, insulin, and leptin, peripheral blood mononuclear cell production of IL-1 beta, IL-6, and tumor necrosis factor, and urinary excretion of proteolysis inducing factor. After 3 wk of consumption of the fish oil-enriched nutritional supplement, there was a significant fall in production of IL-6 (from median 16.5 to 13.7 ng/ml, P = 0.015), a rise in serum insulin concentration (from 3.3 to 5.0 mU/l, P = 0.0064), a fall in the cortisol-to-insulin ratio (P = 0.0084), and a fall in the proportion of patients excreting proteolysis inducing factor (from 88% to 40%, P = 0.008). These changes occurred in association with weight gain (median 1 kg, P = 0.024). Various mediators of catabolism in cachexia are modulated by administration of a fish oil-enriched nutritional supplement in pancreatic cancer patients. This may account for the reversal of weight loss in patients consuming this supplement. [ABSTRACT FROM AUTHOR]

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C-reactive protein) in male patients (n = 40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r = 0.390, p < 0.05), extent of reported weight loss (r = -0.492, p < 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r = 0.686, p < 0.001), and log10 C-reactive protein concentrations (r = -0.545, p < 0.001). On multiple regression analysis, the percent predicted total body potassium and log10 C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r2 = 0.626, p < 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer. [ABSTRACT FROM AUTHOR]

There are few reports on factors that determine survival in advanced gastrointestinal cancer with weight loss. In these patients (n = 91, median weight loss 16.6%), we prospectively examined the importance of metastatic spread, anthropometry, blood parameters, Karnofsky performance status, appetite, and the acute-phase response as predictors of survival. Survival was calculated from date of assessment to the most recent clinic attendance (> or = 30 mo) or until death. On multivariate analysis, metastatic spread (p < 0.05), Karnofsky performance status (p < 0.01), and C-reactive protein concentration (p < 0.001) had independent prognostic value. In locally advanced disease (n = 64), Karnofsky performance status and C-reactive protein concentration remained significant. There was a significantly lower survival in patients with an acute-phase response (median 136 days) than in patients with no response (median 466 days; p < 0.01). Performance status and the acute-phase response are associated, independent of weight loss, with survival duration in advanced gastrointestinal cancer patients. [ABSTRACT FROM AUTHOR]

It has been suggested that resting energy expenditure may be raised in chronic fatigue syndrome due to an upregulation of transmembrane ion transport. We measured resting energy expenditure by indirect calorimetry in 11 women with chronic fatigue and in 11 healthy women. Total body potassium, by whole body counting, and total body water, extracellular water and intracellular water, by a bioelectrical impedance method, were also measured. When individual resting energy expenditure was predicted on the basis of total body potassium values for the chronic fatigue group, 5 out of 11 of these subjects had resting energy expenditure above the upper limit of normal as defined by the control group data. This is consistent with the hypothesis that there is upregulation of the sodium-potassium pump in chronic fatigue syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND: In humans, leptin circulates in a free form and is also bound to macromolecules. The aim of the present study was to compare a rapid acid-ethanol precipitation (AEP) method of measuring bound leptin with the more laborious gel exclusion chromatography (GEC) reference procedure. Serum samples collected from healthy subjects and cancer patients were used in this comparison. METHODS: AEP and GEC methods for measuring leptin binding in serum (from 14 healthy volunteers and 14 patients with advanced non-small cell lung cancer) were adapted from previously published procedures. RESULTS: Intra- and inter-assay precision of the AEP method were 6% (n = 10) and 8% (n = 10), respectively. Bland-Altman analysis of results obtained from the AEP and GEC methods indicated no significant difference in healthy controls. However, significantly higher results were obtained by the AEP method in the cancer patients. CONCLUSIONS: Evaluation of the AEP method revealed that on examination of normal subjects the method was less precise than had previously been reported. Moreover, the method gave differing results in the cancer patients when compared with the GEC method. This study indicates that careful evaluation of any new method for measuring leptin binding requires comparison with a GEC method using the sample matrix of interest. [ABSTRACT FROM AUTHOR]

In the advanced cancer patient, performance status has considerable prognostic power. Karnofsky performance status, together with variables reported to influence its score, was measured in advanced gastrointestinal cancer patients (n = 148). For male and female patients, age, body mass index, weight loss, triceps skinfold thickness, mid-upper arm circumference, albumin, C-reactive protein, and tumor type and stage were regressed against Karnofsky performance status. On multiple regression analysis, only mid-upper arm circumference and log10 C-reactive protein in men (r2 = 0.462, P < 0.0001) and only mid-upper arm circumference and weight loss in women (r2 = 0.485, P < 0.01) were independent predictors of Karnofsky performance status. There was a significant partial correlation, with gender as a covariable, between log10 C-reactive protein and albumin (r = -0.530, P < 0.0001) and mid-upper arm circumference (r = -0.269, P = 0.035) and weight loss (r = 0.286, P = 0.024). The results of the present study indicate that mid-upper arm circumference is a major factor that influences performance status in male and female patients with advanced gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

Abstract: There is increasing evidence that, in most patients with advanced cancer, weight loss is associated with an inflammatory response. To examine the temporal relationship between weight loss, appetite, performance status, and the inflammatory response, 50 patients with advanced gastrointestinal cancer with weight loss were observed for six weeks. Patients were grouped according to whether they had lost weight (>3%, n = 16), were weight stable (<3% change, n = 25), or gained weight (>3%, n = 9). At baseline, the group that subsequently lost weight had lower albumin and higher C-reactive protein concentrations (p < 0.05). On follow-up, there was an increase in C-reactive protein concentration and reductions in triceps skinfold thickness and Karnofsky performance status in the weight-losing group (p < 0.05). In contrast, Karnofsky performance status was improved in the group that gained weight (p < 0.05). Over the six to eight weeks, there was a difference in the changes of triceps skinfold thickness (p < 0.05) and Karnofsky performance status (p < 0.01) between the two groups. These results suggest that loss or gain of >2.5 kg over a six- to eight-week period is required to produce a significant alteration in performance status in weight-losing patients with gastrointestinal cancer. Moreover, the results suggest that the presence of an inflammatory response is associated with further weight loss and the deterioration of performance status. [ABSTRACT FROM AUTHOR]

Background: An association between preoperative markers of systemic inflammation and inferior mortality following abdominal aortic aneurysm (AAA) repair has been observed. The prognostic value of the postoperative inflammatory response remains unreported in patients with AAA. This study aimed to describe the association between the perioperative inflammatory response and mortality in patients undergoing endovascular aneurysm repair and open surgical repair (OSR) for infrarenal AAA., Methods: Consecutive patients undergoing either emergency (endovascular aneurysm repair or OSR) or elective (OSR) intervention for infrarenal AAA were retrospectively recruited from 3 centers. Preoperative systemic inflammation was assessed using the modified Glasgow Prognostic Score. Day 3 postoperative C-reactive protein (CRP) (≤300 mg/L, >300 mg/L) was chosen as the covariate of interest. The primary outcome was 30-day mortality in the emergency cohort and 12-month mortality in the elective cohort., Results: There were 167 emergency cases (120 (72%) OSR) and 207 elective (207 (100%) OSR) cases, with a median (interquartile range) follow-up of 85 (52) months in the emergency cohort and 63 (57) months in the elective cohort. There were 56% versus 44% of patients in the emergency cohort day 3 CRP ≤300 mg/l versus >300 mg/L compared with 82% versus 18% of patients in the elective cohort (P < 0.001). On univariate binary logistic regression analyses in the emergency cohort, open repair (P < 0.05), preoperative modified Glasgow Prognostic Score 2 (P < 0.05), postoperative mesenteric ischemia (P < 0.01), and day 3 postoperative CRP >300 mg/L (P < 0.05) were associated with increased odds of 30-day mortality. On multivariate binary logistic regression analyses, only preoperative modified Glasgow Prognostic Score 2 (odds ratio [OR]: 2.11, 95% confidence interval [CI]: 1.12-3.98, P < 0.05) retained independent association with 30-day mortality. In the elective cohort, mean (95% CI) survival in the day 3 CRP ≤300 mg/l versus >300 mg/L was 112.0 (101.8-122.2) months versus 67.2 (54.1-80.2) months (P < 0.001). On univariate binary logistic regression analyses in the elective cohort, age ≥75 (P < 0.05), ischemic heart disease (P < 0.05), and day 3 postoperative CRP >300 mg/L (P < 0.001) were associated with increased odds of 12-month mortality. On multivariate binary logistic regression analyses, both age ≥75 (OR: 5.15, 95% CI: 1.25-21.30, P < 0.05) and day 3 postoperative CRP >300 mg/L (OR: 15.68, 95% CI: 3.61-68.15, P < 0.001) retained independent association with 12-month mortality., Conclusions: Preoperative and postoperative markers of systemic inflammation were independently associated with inferior survival following emergency and elective repair of AAA, respectively. Further investigation of the perioperative systemic inflammatory response is warranted in this patient group, with a particular focus on identifying targets for intervention., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: CT-derived measures of body composition have been shown to have prognostic value in patients with cancer. However, few studies have compared these observations across tumor types and stages of disease. The aim of the present study was to compare body composition measures between two types of cancers, i.e. colorectal cancer (CRC), which is less inflammatory and patients maintain body composition over a longitudinal study period, whereas lung cancer (LC) is proinflammatory and patients lose more fat and muscle mass using a standard methodology., Methods: Clinicopathological characteristics, including those pertaining to nutritional risk/status and systemic inflammation in patients with colorectal cancer (CRC, n  = 1047) and lung cancer (LC, n  = 662), were compared. The CT image at L3 was used to assess body composition. Comparison of these cohorts was carried out using the chi-square test. Binary logistic regression analysis was performed to assess the impact of clinico-pathological variables on body composition, and scatter plots were used to examine the relationship between body mass index (BMI) and CT-derived measures of body composition., Results: According to CT-derived body composition, high subcutaneous (SFI) and visceral fat index (VFI) were common (>70%) in both CRC and LC. Also, low skeletal muscle index (SMI) and density (SMD) were approximately 40-50% and 60-70% in both CRC and LC. Compared with CRC, patients with LC had a higher American Society of Anaesthesia (ASA) ( P  < 0.001), Malnutrition Universal Screening Tool (MUST) ( P  < 0.001), modified frailty index (mFI) ( P  < 0.001), modified Glasgow Prognostic Score (mGPS) ( P  < 0.001), and neutrophil lymphocyte ratio (NLR) ( P  < 0.001) scores.On binary logistic regression analysis, MUST, mFI, and NLR were predictors of subcutaneous adiposity ( P  < 0.05); type of cancer, MUST, and mFI were predictors of visceral obesity ( P  < 0.001); age, type of cancer, MUST, and mGPS were predictors of low SMI ( P  < 0.001); and age, type of cancer, mFI, and mGPS were predictors of low SMD ( P  < 0.05). There was a similar relationship between BMI and other measures of CT-derived body composition across two types of cancers., Conclusion: Obesity and low skeletal muscle mass were common in both CRC and LC cohorts despite large differences in comorbidity, nutritional risk, systemic inflammation, and survival, even when normalized for TNM stage. These observations would support the hypothesis that, although prognostic, CT derived body composition analysis primarily reflects patient constitution rather than the effect of tumor stage in patients with cancer. The systemic inflammatory response, as evidenced by mGPS, can be considered as an important therapeutic target and loss of muscle mass in patients with advanced cancer is related to the systemic inflammatory response.

Purpose: Carbonic anhydrase IX (CAIX) is a well-established prognostic marker in breast cancer (BC). Nevertheless, this prognostic value is yet to be confirmed in BC subtypes. This study aims to investigate the prognostic effects of CAIX in oestrogen receptor (ER)-negative (ER-) BCs and to establish pathways related to cytoplasmic CAIX expression in ER- and lymph node-negative BCs., Methods: Immunohistochemistry was performed to identify the prognostic role of CAIX protein expression in ER- tissue microarrays (TMAs) (n = 191). CAIX-positive samples (n = 37) were transcriptionally profiled by TempO-Seq and analysed by STRING. Real-time quantitative PCR (RT-qPCR) analysis was used to validate differentially expressed genes., Results: Overexpression of cytoplasmic CAIX was an independent predictor of recurrence free survival, disease-free survival and overall survival in ER- cohort. RNA transcriptomic analysis identified 10 significant genes in ER- cohort and 3 genes in the node-negative group. The STRING database demonstrated a significant interaction between MUCL1 and GALNT6, which were linked with extracellular matrix organisation, degradation of the extracellular matrix and disease of glycosylation pathways. In the node-negative group, SPNS2 is mainly involved in the sphingolipid de novo biosynthesis pathway. A significant correlation between cytoplasmic SphK1 and cytoplasmic hypoxia-inducible factor-1α was observed. Among the 10 genes, 7 genes (SERHL2, GALNT6, MUCL1, MMP7, PITX2, CEACAM6 and SPNS2) were selected, and their expression was quantitatively assessed by RT-qPCR. The PCR data of these genes showed that SERHL2, GALNT6, MUCL1, PITX2, and SPNS2 mRNA levels were expressed in MDA-MB-231 BC cell lines at variable levels of hypoxic exposure., Conclusion: Cytoplasmic CAIX was independently associated with poor prognosis in ER- BC. Gene expression profiles shed light on the pathways and genes associated with hypoxia in ER- BC. In node-negative patients, SPNS2 was of particular interest., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Body composition assessment using CT images at the L3-level is increasingly applied in cancer research and has been shown to be strongly associated with long-term survival. Robust high-throughput automated segmentation is key to assess large patient cohorts and to support implementation of body composition analysis into routine clinical practice. We trained and externally validated a deep learning neural network (DLNN) to automatically segment L3-CT images., Methods: Expert-drawn segmentations of visceral and subcutaneous adipose tissue (VAT/SAT) and skeletal muscle (SM) of L3-CT-images of 3187 patients undergoing abdominal surgery were used to train a DLNN. The external validation cohort was comprised of 2535 patients with abdominal cancer. DLNN performance was evaluated with (geometric) dice similarity (DS) and Lin's concordance correlation coefficient., Results: There was a strong concordance between automatic and manual segmentations with median DS for SM, VAT, and SAT of 0.97 (IQR: 0.95-0.98), 0.98 (IQR: 0.95-0.98), and 0.95 (IQR: 0.92-0.97), respectively. Concordance correlations were excellent: SM 0.964 (0.959-0.968), VAT 0.998 (0.998-0.998), and SAT 0.992 (0.991-0.993). Bland-Altman metrics indicated only small and clinically insignificant systematic offsets; SM radiodensity: 0.23 Hounsfield units (0.5%), SM: 1.26 cm2.m-2 (2.8%), VAT: -1.02 cm2.m-2 (1.7%), and SAT: 3.24 cm2.m-2 (4.6%)., Conclusion: A robustly-performing and independently externally validated DLNN for automated body composition analysis was developed., Advances in Knowledge: This DLNN was successfully trained and externally validated on several large patient cohorts. The trained algorithm could facilitate large-scale population studies and implementation of body composition analysis into clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Background: The review discusses the significant impact of cancer on patients, particularly focusing on cachexia - a condition marked by weight and lean tissue loss. This condition critically affects the nutritional status, quality of life, and treatment outcomes of cancer patients., Research Question: The review seeks to understand the effectiveness and necessity of routine clinical monitoring of cancer cachexia, and how it can aid in better therapeutic interventions., Methods: The systematic review followed a pre-defined protocol based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)statement. A systematic search using specific keywords was conducted in PubMed and EMBASE databases on October 24, 2023, supplemented by citations from the original papers. The selection process involved screening titles and abstracts for relevance., Results: The review finds varying levels of effectiveness in the different measurement criteria used for monitoring cachexia. It highlights the potential of the Global Leadership Initiative on Malnutrition (GLIM) framework in defining and managing cancer cachexia, though noting some challenges in standardisation and implementation of measurements., Conclusion: The present systematic review highlights the variability and lack of standardization in the application of GLIM criteria for monitoring cachexia in cancer patients. Despite these challenges, it will be important to determine the most efficacious clinically routine nutritional and inflammation assessments in the routine application of GLIM criteria assessment., Competing Interests: Declaration of competing interest We declare that there are no conflicts of interest regarding the publication of this paper. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Transforming growth factor β-activated protein kinase-1 (TAK1) plays an important role in MAPK and NFκB pathways and has been associated with colorectal cancer. The aim of this study was to determine how cytoplasmic and juxtanuclear punctate staining of TAK1 relates to immune checkpoint expression and cancer specific survival in colorectal cancer., Methods: Protein expression was assessed by immunohistochemistry on tissue microarrays from primary curative colorectal cancer resected specimens. Expression levels of cytoplasmic TAK1 by QuPath digital quantification and punctate TAK1 staining was scored using a manual point scoring technique and correlated with clinicopathological features, immune checkpoint expression and cancer-specific survival. Bulk RNA sequencing was performed in specimens to determine mutational profiles and differentially expressed genes., Results: A cohort of 875 patients who had undergone colorectal cancer resection were assessed for TAK1 expression. Higher levels of cytoplasmic TAK1 expression correlated with elevated PD1 and PD-L1 expression (p < 0.010). High punctate TAK1 expression was more commonly identified in poorly differentiated colorectal cancers (p = 0.036), had dysregulated mutational and transcriptional profiles with decreased insulin-like growth factor 2(IGF2) expression (p < 0.010), and independently predicted poor cancer-specific survival (HR 2.690, 95% CI 1.419-5.100, p = 0.002). The association of punctate TAK1 expression and recurrence remained after subgroup analysis for microsatellite-stable colorectal cancer (p = 0.028)., Discussion: Punctate TAK1 expression is associated with worse cancer specific survival. TAK1 signalling may be an important pathway to investigate underlying mechanisms for recurrence in microsatellite-stable colorectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Sarcopenia appears to be associated with inferior outcomes in surgical conditions. Chronic systemic inflammation confers an inferior long-term prognosis in cardiovascular disease and is associated with the development of sarcopenia. The aim of this study was to describe the prognostic role of sarcopenia assessed using computed tomography (CT)-derived body composition analysis and systemic inflammation in patients undergoing carotid endarterectomy for symptomatic carotid stenosis., Methods: In this retrospective cohort study, patients undergoing carotid endarterectomy for symptomatic carotid stenosis between 1 January 2011 and 1 October 2021 at four referral centres were included. The C3 skeletal muscle index and C3 skeletal muscle density were recorded from preoperative CT images. Systemic inflammation was assessed using the preoperative systemic inflammatory grade (SIG). The primary outcome was overall mortality during the study interval., Results: A total of 618 patients were included, with a median follow-up of 69 (interquartile range 34-85) months. On univariable analysis, age greater than or equal to 75 years (P < 0.001), American Society of Anesthesiologists (ASA) grade greater than II (P < 0.001), low C3 skeletal muscle index (P = 0.002), low C3 skeletal muscle density (P < 0.001), SIG greater than or equal to 2 (P < 0.001), and low L3 derived skeletal muscle index (P < 0.001) were associated with increased mortality, whereas body mass index greater than or equal to 25 kg/m2 was associated with decreased mortality (P = 0.023). On multivariable analysis, age 75 years or older (HR 2.17 (95% c.i. 1.58 to 2.97), P < 0.001), ASA grade greater than II (HR 2.06 (95% c.i. 1.35 to 3.12), P < 0.001), low C3 skeletal muscle density (HR 1.84 (95% c.i. 1.33 to 2.54), P < 0.001), and SIG greater than or equal to 2 (HR 1.63 (95% c.i. 1.33 to 1.99), P < 0.001) were independently associated with increased mortality., Conclusion: Cervical CT-derived muscle mass and density, and markers of systemic inflammation, such as systemic inflammatory grade, may be associated with an inferior long-term prognosis after carotid endarterectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Purpose of Review: The following article examines the rationale for an inflammation-first approach for diagnosing cachexia and how the current Global Leadership Initiative on Malnutrition (GLIM) framework may be adapted to facilitate this., Recent Findings: Recently, the GLIM have published guidance on the measurement of inflammation in the context of cachexia, advocating that C-reactive protein (CRP) should be utilized for quantification. The inclusion of a systemic inflammatory biomarker for the diagnosis of cachexia questions whether it may be more aptly considered a systemic inflammatory syndrome., Summary: The current consensus of the GLIM is that cachexia is 'disease-related malnutrition with inflammation'. In line with this definition, the GLIM proposed a two-step diagnostic framework: screening for malnutrition using validated screening tools and then confirming the presence of disease-related malnutrition with phenotypic (nonvolitional weight loss, low BMI, and reduced muscle mass) and aetiologic criterion reduced food intake/assimilation, and inflammation or disease burden). The GLIM are to be commended for guidance on the measurement of systemic inflammation in their current proposal, given the relative importance to clinical outcomes in patients with cancer. However, the use of CRP is somewhat rudimentary and contrasts other cancer cachexia guidelines and contemporary clinical cancer research., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Activation of the systemic inflammatory response (SIR) is associated with inferior outcomes across a spectrum of disease. Routinely available measures of the SIR (neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory grade (SIG)) have been shown to provide prognostic value in patients undergoing surgical intervention. The present study aimed to review the literature describing the prognostic association of NLR, PLR, SII and SIG in patients undergoing intervention for abdominal aortic aneurysm (AAA)., Methods: This PRISMA guidelines were followed. The MEDLINE database was interrogated for relevant studies investigating the effect of peri-operative systemic inflammation-based prognostic systems on all-cause mortality in patients undergoing OSR and EVAR for AAA. Inter-study heterogeneity precluded meaningful meta-analysis; qualitative analysis was instead performed., Results: There were 9 studies included in the final review reporting outcomes on a total of 4571 patients; 1256 (27 %) patients underwent OSR, and 3315 (73 %) patients underwent EVAR. 4356 (95 %) patients underwent a procedure for unruptured AAA, 215 (5 %) patients underwent an emergency procedure for ruptured AAA0.5 studies reported early (inpatient or 30-day) mortality; 2 of these found that elevated NLR predicted inferior survival, however PLR did not provide prognostic value. 6 studies reported long-term mortality; elevated NLR (5 studies), PLR (1 study), and SIG (1 study) predicted inferior survival., Conclusions: It appears that activation of the SIR is associated with inferior prognosis in patients undergoing intervention for AAA, however the evidence is limited by heterogenous methodology and lack of consensus regarding optimal cutoff., Prospero Database Registration Number: CRD42022363765., Competing Interests: Declaration of competing interest Nicholas A Bradley, Campbell S D Roxburgh, Donald C McMillan, and Graeme J K Guthrie declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The present study sought to examine the relationships between systemic inflammatory composite ratios/cumulative scores, magnitude of systemic inflammatory response (SIR) and survival in good performance status patients (ECOG-PS 0/1) with advanced NSCLC receiving palliative radiotherapy., Methods: Systemic inflammatory composite ratios/cumulative scores included the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein, (CRP)-albumin ratio (CAR), neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil-platelet score (NPS), modified Glasgow prognostic score (mGPS). The magnitude of SIR was determined by serum CRP concentration, with a median CRP concentration of >10 m mg/L considered to be systemically inflamed. Relationships between systemic inflammatory composite ratios/ cumulative scores and clinicopathological characteristics were examined using chi-square analysis. Relationships between overall survival (OS) and systemic inflammatory composite ratios/ cumulative scores were examined using cox regression analysis., Results: 479 patients were included. 48% (n = 231) of patients were male and 70% (n = 338) were ≥65 years of age. 29% (n = 140) patients were ECOG-PS 0 and 71% (n = 339) were ECOG-PS 1. 98% (n = 469) of patients died during follow-up. The median survival was 5 months (2-11). A similar prevalence of systemic inflammation was noted across the various ratios/scores (NLR >3 68%; LMR <2.4 65%; PLR >150 70%; CAR >0.20 83%; NLS ≥1 66%; LMS ≥1 71%; NPS≥1 50%; PLS≥1 60% and mGPS≥1 75%). Despite not considered to be systemically inflamed, an NLR <3, LMR ≥2.4, PLR ≤150, NLS 0, LMS 0, NPS 0 and PLS 0 all had a median CRP concentration of >10 mg/L. When adjusted for ECOG-PS, CAR>0.40 (p < 0.001) and mGPS 2 (p < 0.05) remained significantly associated with OS., Conclusion: Liver-based measures of systemic inflammation (CAR and mGPS) appear more reliable for the quantification of the magnitude of SIR and have prognostic value in patients with advanced NSCLC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Low skeletal muscle index/density (SMI/SMD) is prevalent in cancer, adversely prognostic and associated with tumour stage and the systemic inflammatory response (SIR). Age and SMI/SMD has not been widely studied. The present study analyses the association between age and SMI/SMD after adjustment for other clinicopathological factors. Patients undergoing resectional surgery for TNM Stage I-III disease within the West of Scotland between 2011 and 2014 were identified. A single CT slice was obtained from each patients staging CT scan. SMI and SMD were stratified normal/abnormal. The SIR was stratified using Systemic Inflammatory Grade (SIG). When stratified by age (< 50/50s/60s/70s/80+), 39%/38%/48%/62%/74% and 27%/48%/64%/82%/92% of patients had a low SMI and SMD respectively (both p < 0.001). Older age (OR 1.47, p < 0.001), female sex (OR 1.32, p = 0.032), lower socioeconomic deprivation (OR 1.15, p = 0.004), higher ASA (OR 1.30, p = 0.019), emergency presentation (OR 1.82, p = 0.003), lower BMI (OR 0.67, p < 0.002) and higher SIG (OR 1.23, p < 0.001) were independently associated with low SMI. Older age (OR 2.28, p < 0.001), female sex (OR 1.38, p = 0.038), higher ASA (OR 1.92, p < 0.001), emergency presentation (OR 1.71, p = 0.023), and higher SIG (OR 1.37, p < 0.001) were independently associated with lower SMD. Tumour factors were not independently associated with either SMI/SMD. Age was a major factor associated with low SMI/SMD in patients with colon cancer. Therefore, in these patients it is likely that this represents largely constitutional body composition as opposed to being a disease mediated effect. Adjustment for age is required when considering the cancer mediated effect on SMI/SMD in patients with colon cancer., (© 2024. The Author(s).)

Introduction: Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed., Methods: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS)., Results: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29-2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p<0.00001) or CRP (HR 1.55, 1.43 - 1.69; p<0.00001)., Conclusion: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Frailty is a chronic condition with complex etiology and impaired functional performance that has been associated with altered body composition and chronic inflammation. Chronic limb-threatening ischemia (CLTI) carries significant morbidity and mortality and is associated with poor quality of life. The present study aims to examine these relationships and their prognostic value in patients with CLTI., Methods: Consecutive patients presenting as unscheduled admissions to a single tertiary center with CLTI were included over a 12-month period. Frailty was diagnosed using the Clinical Frailty Scale (CFS). Body composition was assessed using computerised tomography (CT) at the L3 vertebral level (CT-BC) to generate visceral and subcutaneous fat indices, skeletal muscle index, and skeletal muscle density. Skeletal muscle index and skeletal muscle density were combined to form the CT-sarcopenia score (CT-SS). Systemic inflammation was assessed by the modified Glasgow prognostic score (mGPS). The primary outcome was overall mortality., Results: There were 190 patients included with a median (interquartile range) follow-up of 22 (6) months (range 15-32 months) and 79 deaths during the follow-up period. One hundred patients (53%) had a CFS >4. CFS >4 (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.25-3.66, P < 0.01), CT-SS (HR 1.47, 95% CI 1.03-2.09, P < 0.05), and mGPS (HR 1.54, 95% CI 1.11-2.13, P < 0.01) were independently associated with increased mortality. CT-SS (odds ratio 1.88, 95% CI 1.09-3.24, P < 0.01) was independently associated with CFS >4. Patients with CT-SS 0 and CFS ≤4 had 90% (standard error [SE] 5%) 1-year survival, compared with 35% (SE 9%) in patients with CT-SS 2 and CFS >4 (P < 0.001). Patients with mGPS 0 and CFS ≤4 had 94% (SE 4%) 1-year survival compared with 44% (SE 6%) in the mGPS 2 and CFS >4 subgroup (P < 0.001)., Conclusions: Frailty assessed by CFS was associated with CT-BC. CFS, CT-SS, and mGPS were associated with poorer survival in patients presenting as unscheduled admissions with CLTI. CT-SS and mGPS may contribute to part of frailty and prognostic assessment in this patient cohort., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cardio-pulmonary exercise testing (CPEX) is selectively used before intervention for abdominal aortic aneurysm (AAA). Sarcopenia, a chronic condition defined by reduced skeletal muscle function and volume, can be assessed radiologically by computed tomography (CT)-derived body composition analysis (CT-BC), and is associated with systemic inflammation., Objective: The aim was to describe the association between CT-BC, CPEX, inflammation and survival in patients undergoing elective intervention for AAA., Setting: Patients were recruited retrospectively from a single, secondary-care centre-operative database. Cases undergoing elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR) between 31 March 2015 and 25 June 2020 were included., Patients: There were 176 patients (130 EVAR, 46 OSR) available for analysis in the final study; median (interquartile range [IQR]) follow-up was 60.5 [27] months, and all completed a minimum of 2 years follow-up., Main Outcome Measures: Preoperative CPEX tests were recorded. CT sarcopenia score [CT-SS, range 0 to 2, calculated based on normal/low SMI (0/1) and normal/low SMD (0/1)] assessed radiological sarcopenia. Preoperative modified Glasgow Prognostic score (mGPS) was used to assess systemic inflammation., Results: Mean [95% confidence interval (CI) survival in the CT-SS 0 vs. CT-SS 1 vs. CT-SS 2 subgroups was 80.1 (73.6 to 86.6) months vs. 70.3 (63.5 to 77.1) months vs. 63.8 (53.4 to 74.2) months] ( P  = 0.01). CT-SS was not associated with CPEX results ( P  > 0.05). Elevated CT-SS [hazard ratio (HR) 1.83, 95% CI, 1.16 to 2.89, P  < 0.01] was independently associated with increased hazard of long-term mortality; however, CPEX results were not ( P  > 0.05)., Conclusion: CPEX test results were not consistently associated with body composition and did not have significant prognostic value in patients undergoing elective treatment for AAA., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Purpose: The purpose of this study is to evaluate the association between hyperparathyroidism (PHPT), parathyroid hormone levels, and calcium levels in patients diagnosed with benign fibro-osseous lesions such as fibrous dysplasia (FD), ossifying fibroma (OF), central giant cell granulomas (GCG)., Methods: This is a retrospective, single-center study from a sample of patients who underwent surgical treatment of FD, OF, and GCG at Mayo Clinic between 1996 and 2021. Patient demographics, history of PHPT, histopathological diagnosis, and relevant laboratory values such as parathyroid hormone (PTH), serum calcium, vitamin D, and alkaline phosphatase were collected., Results: Of the patients diagnosed with FD (n = 64), OF (n = 24), and GCG (n = 5), a diagnosis of PHPT was found in 2 patients (3.1%), 1 patient (4.2%), and 0 patients (0%), respectively. Elevated PTH levels (>65 pg/mL) were observed in 3 patients (4.7%) with FD, 1 patient (4.2%) with OF, and 1 patient (20%) with GCG. Mean (standard deviation) calcium levels were 9.3 (0.6) mg/dL in the FD group, 9.4 (0.5) mg/dL in the OF group, and 9.3 (0.6) mg/dL in the GCG group. Patients with fibro-osseous jaw tumors including FD, OF, and GCG may have increased risk of PHPT compared to the general population., Conclusion: Patients with benign jaw tumors including FD, OF, and GCG may have increased risk of PHPT compared to the general population. Surgeons treating these benign tumors need to be cognizant of these findings, obtain appropriate laboratory studies, and incorporate multidisciplinary care including endocrinologists, endocrine surgeons, and maxillofacial surgeons., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Lower extremity arterial disease (LEAD) is caused by atherosclerotic plaque in the arterial supply to the lower limbs. The neutrophil to lymphocyte and platelet to lymphocyte ratios (NLR, PLR) are established markers of systemic inflammation which are related to inferior outcomes in multiple clinical conditions, though remain poorly described in patients with LEAD. This review was carried out in accordance with PRISMA guidelines. The MEDLINE database was interrogated for relevant studies. Primary outcome was the prognostic effect of NLR and PLR on clinical outcomes following treatment, and secondary outcomes were the prognostic effect of NLR and PLR on disease severity and technical success following revascularisation. There were 34 studies included in the final review reporting outcomes on a total of 19870 patients. NLR was investigated in 21 studies, PLR was investigated in two studies, and both NLR & PLR were investigated in 11 studies. Relating to increased levels of systemic inflammation, 20 studies (100%) reported inferior clinical outcomes, 13 (92.9%) studies reported increased disease severity, and seven (87.5%) studies reported inferior technical results from revascularisation. The studies included in this review support the role of elevated NLR and PLR as key components influencing the clinical outcomes, severity, and success of treatment in patients with LEAD. The use of these easily accessible, cost effective and routinely available markers is supported by the present review.

Introduction: There is growing evidence that the use of robotic-assisted surgery (RAS) in colorectal cancer resections is associated with improved short-term outcomes when compared to laparoscopic surgery (LS) or open surgery (OS), possibly through a reduced systemic inflammatory response (SIR). Serum C-reactive protein (CRP) is a sensitive SIR biomarker and its utility in the early identification of post-operative complications has been validated in a variety of surgical procedures. There remains a paucity of studies characterising post-operative SIR in RAS., Methods: Retrospective study of a prospectively collected database of consecutive patients undergoing OS, LS and RAS for left-sided and rectal cancer in a single high-volume unit. Patient and disease characteristics, post-operative CRP levels, and clinical outcomes were reviewed, and their relationships explored within binary logistic regression and propensity scores matched models., Results: A total of 1031 patients were included (483 OS, 376 LS, and 172 RAS). RAS and LS were associated with lower CRP levels across the first 4 post-operative days (p < 0.001) as well as reduced complications and length of stay compared to OS in unadjusted analyses. In binary logistic regression models, RAS was independently associated with lower CRP levels at Day 3 post-operatively (OR 0.35, 95% CI 0.21-0.59, p < 0.001) and a reduction in the rate of all complications (OR 0.39, 95% CI 0.26-0.56, p < 0.001) and major complications (OR 0.5, 95% CI 0.26-0.95, p = 0.036). Within a propensity scores matched model comparing LS versus RAS specifically, RAS was associated with lower post-operative CRP levels in the first two post-operative days, a lower proportion of patients with a CRP ≥ 150 mg/L at Day 3 (20.9% versus 30.5%, p = 0.036) and a lower rate of all complications (34.7% versus 46.7%, p = 0.033)., Conclusions: The present observational study shows that an RAS approach was associated with lower postoperative SIR, and a better postoperative complications profile., (© 2024. The Author(s).)

Background: Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned., Methods: Consecutive patients newly diagnosed with locally advanced (T3-4 or at least N1) oesophagogastric cancer between 1 January 2010 and 31 December 2015 were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil lymphocyte ratio). Sex-stratified cut-off values were determined based on the area under the curve (AUC), and patients were divided into groups with low or normal CXI. Primary outcomes were disease progression during neoadjuvant chemotherapy and overall survival (at least 5 years of follow-up)., Results: Overall, 385 patients (72% men, median age 66 years) were treated with neoadjuvant chemotherapy for oesophageal (274) or gastric (111) cancer across the study interval. Although patients with a low CXI (men: CXI below 52 (AUC 0.707); women: CXI below 41 (AUC 0.759)) were older with more co-morbidity, disease characteristics were comparable to those in patients with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with a low CXI (28 versus 12%; adjusted OR 3.07, 95% c.i. 1.67 to 5.64; P < 0.001). Low CXI was associated with worsened postoperative mortality (P = 0.019) and decreased overall survival (median 14.9 versus 56.9 months; adjusted HR 1.85, 1.42 to 2.42; P < 0.001)., Conclusion: CXI is associated with disease progression, worse postoperative mortality, and overall survival, and could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)