Cachexia index for prognostication in surgical patients with locally advanced oesophageal or gastric cancer: multicentre cohort study.

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.

Robotic-assisted surgery for left-sided colon and rectal resections is associated with reduction in the postoperative surgical stress response and improved short-term outcomes: a cohort study.

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.

Management of malignant T1 colorectal cancer polyps: results from a 10-year prospective observational study.

AIM: The recurrence risk associated with residual malignant cells (bowel wall/regional nodes) following T1 colorectal cancer (CRC) polypectomy must be weighed against operative morbidity. Our aim was to describe the management and outcomes of a large prospective cohort of T1 CRCs. METHOD: All T1 CRCs diagnosed between March 2007 and March 2017 at the Glasgow Royal Infirmary were included. Patients were grouped by polypectomy, rectal local excision and formal resection status. χ2 testing, multivariate binary logistic and Cox regression were performed. RESULTS: Of 236 patients, 90 (38.1%) underwent polypectomy only, six (2.6%) polypectomy and then rectal excision, 57 (24.2%) polypectomy and then resection, 14 (5.9%) rectal excision only and 69 (29.2%) primary resection. Polypectomy only correlated with male sex (P = 0.028), older age (P < 0.001), distal CRCs (P < 0.001) and pedunculated polyps (P < 0.001); primary resection with larger polyps (P < 0.001); polypectomy then resection with piecemeal excision (P = 0.002) and involved polypectomy margin (P < 0.001). Poor differentiation (OR 7.860, 95% CI 1.117-55.328; P = 0.038) independently predicted lymph node involvement. Submucosal venous invasion (hazard ratio [HR] 10.154, 95% CI 2.087-49.396; P = 0.004) and mucinous subtype (HR 7.779, 95% CI 1.566-38.625; P = 0.012) independently predicted recurrence. Submucosal venous invasion (HR 5.792, 95% CI 1.056-31.754; P = 0.043) predicted CRC-specific survival. Although 64.4% of polypectomy-only patients had margin involvement/other risk factors, none developed recurrence. Of 94 with polypectomy margin involvement, five (5.3%) had confirmed residual tumour. Overall, lymph node metastases (7.1%), recurrence (4.2%) and cancer-specific mortality (3.0%) were rare. Cancer-specific 5-year survival was high: polypectomy only (100%), polypectomy and then resection (98.2%), primary resection (100%). CONCLUSION: Surveillance may be safe for more T1 CRC polyp patients. Multidisciplinary team discussion and informed patient choice are critical.

Risk stratification for the detection of metachronous polyps after bowel screening polypectomy: clinical outcomes from the Integrated Technologies for Improved Polyp Surveillance (INCISE) study cohort.

BACKGROUND: After colorectal polypectomy, 20-50 per cent of patients develop metachronous polyps and some have increased colorectal cancer risk. British Society of Gastroenterology (BSG) 2020 guidelines recommend surveillance colonoscopy for high-risk patients based on index pathology. The aim of this study was to evaluate metachronous lesion outcome using BSG 2020 criteria. METHODS: A retrospective, multicentred study was conducted including patients who had polypectomy during screening colonoscopy (2009-2016) followed by surveillance. Demographics, index pathology, and BSG 2020 risk criteria were compared with regard to metachronous lesion pathology (non-advanced versus advanced lesions) and timing of detection (early versus late). Advanced lesions were defined as adenomas/serrated polyps greater than or equal to 10 mm, high-grade dysplasia, serrated polyps with dysplasia, or colorectal cancer, and late lesions those detected greater than 2 years after the index procedure. RESULTS: Of 3090 eligible patients, 2643 were included. Among these, retrospective BSG 2020 application would have excluded 51.5 per cent from surveillance. After a median of 36 months, the advanced polyp/colorectal cancer rate in BSG 2020 high-risk patients was 16.3 versus 13.0 per cent in low-risk patients. Older age (P = 0.008) correlated with advanced metachronous lesions. Male sex, greater than five polyps, and BSG 2020 high-risk criteria correlated with non-advanced and advanced lesions (P < 0.001). Older age (P < 0.001), villous features (P = 0.006), advanced index polyp (P = 0.020), and greater than five polyps (P < 0.001) correlated with early metachronous lesions. Male sex and BSG 2020 high-risk criteria correlated with early and late lesions (P < 0.001). On multivariable regression, increased polyp number (odds ratio (OR) 1.15 (95 per cent c.i. 1.07 to 1.25); P < 0.001) and villous features (OR 1.49 (95 per cent c.i. 1.05 to 2.10); P = 0.025) independently correlated with early advanced lesions. The rate of non-advanced and advanced metachronous polyps was higher in BSG 2020 high- versus low-risk patients (44.4 versus 35.4 per cent for non-advanced and 15.7 versus 11.8 per cent for advanced; P < 0.001), but the colorectal cancer rate was similar (0.6 versus 1.2 per cent). However, when examining only lesions detected greater than 2 years after the index colonoscopy in high- versus low-risk patients, no significant differences were observed (P = 0.140). CONCLUSION: BSG 2020 criteria correlated with metachronous polyps, but did not differentiate advanced and non-advanced lesions and were not predictive of late lesions.

Prevalence of repeat faecal immunochemical testing in symptomatic patients attending primary care.

AIM: The faecal immunochemical test (FIT) for faecal haemoglobin (f-Hb) helps determine the risk of colorectal cancer (CRC) and has been integrated into symptomatic referral pathways. 'Safety netting' advice includes considering referral for persistent symptoms, but no published data exists on repeated FITs. We aimed to examine the prevalence of serial FITs in primary care and CRC risk in these patients. METHOD: A multicentre, retrospective, observational study was conducted of patients with two or more consecutive f-Hb results within a year from three Scottish Health Boards which utilize FIT in primary care. Cancer registry data ensured identification of CRC cases. RESULTS: Overall, 135 396 FIT results were reviewed, of which 12 359 were serial results reported within 12 months (9.1%), derived from 5761 patients. Of these, 42 (0.7%) were diagnosed with CRC. A total of 3487 (60.5%) patients had two f-Hb < 10 µg/g, 944 (16.4%) had f-Hb ≥ 10 µg/g followed by <10 µg/g, 704 (12.2%) f-Hb < 10 µg/g followed by ≥10 µg/g and 626 (10.9%) had two f-Hb ≥ 10 µg/g. The CRC rate in each group was 0.1%, 0.4%, 1.4% and 4.0%, respectively. Seven hundred and thirty four patients submitted more than two FITs within a year. The likelihood of one or more f-Hb ≥ 10 µg/g rose from 40.4% with two samples to 100% with six, while the CRC rate fell from 0.8% to 0%. CONCLUSION: Serial FITs within a year account for 9.1% of all results in our Boards. CRC prevalence amongst symptomatic patients with serial FIT is lower than in single-FIT cohorts. Performing two FITs within a year for patients with persistent symptoms effectively acts as a safety net, while performing more than two within this timeframe is unlikely to be beneficial.

Alternative diagnoses and demographics associated with a raised quantitative faecal immunochemical test in symptomatic patients.

BACKGROUND: The faecal immunochemical test (FIT) has proven utility for colorectal cancer detection in symptomatic patients. However, most patients with a raised faecal haemoglobin (f-Hb) do not have colorectal cancer. We investigated alternative diagnoses and demographics associated with a raised f-Hb in symptomatic patients. METHODS: A retrospective, observational study was performed of patients with FIT submitted between August 2018 to January 2019 in NHS Greater Glasgow and Clyde followed by colonoscopy. Colonoscopy/pathology reports were searched for alternative diagnoses. Covariables were compared using the χ2 test. Multivariate binary logistic regression identified independent predictors of a raised f-Hb. RESULTS: 1272 patients were included. In addition to colorectal cancer (odds ratio (OR), 9.27 (95% confidence interval (CI): 3.61-23.83; p < 0.001)), older age (OR, 1.52 (95% CI: 1.00-2.32; p = 0.05)), deprivation (OR, 1.54 (95% CI: 1.21-1.94; p < 0.001)), oral anticoagulants (OR, 1.78 (95% CI: 1.01-3.15; p = 0.046)), rectal bleeding (OR, 1.47 (95% CI: 1.15-1.88; p = 0.002)), advanced adenoma (OR, 7.52 (95% CI: 3.90-14.49; p < 0.001)), non-advanced polyps (OR, 1.78 (95% CI: 1.33-2.38; p < 0.001)) and inflammatory bowel disease (IBD) (OR, 4.19 (95% CI: 2.17-8.07; p < 0.001)) independently predicted raised f-Hb. Deprivation (Scottish Index of Multiple Deprivation (SIMD) 1-2: OR, 2.13 (95% CI: 1.38-3.29; p = 0.001)) independently predicted a raised f-Hb in patients with no pathology found at colonoscopy. CONCLUSIONS: An elevated f-Hb is independently associated with older age, deprivation, anticoagulants, rectal bleeding, advanced adenoma, non-advanced polyps and IBD in symptomatic patients. Deprivation is associated with a raised f-Hb in the absence of pathology. This must be considered when utilising FIT in symptomatic patients.

Combining the quantitative faecal immunochemical test and full blood count reliably rules out colorectal cancer in a symptomatic patient referral pathway.

PURPOSE: Faecal Immunochemical Test (FIT) has proven utility for Colorectal Cancer (CRC) detection in symptomatic patients. Most studies have examined FIT in symptomatic patients subsequently referred from primary care. We investigated associations between CRC and FIT in both referred and non-referred symptomatic patients. METHODS: A retrospective, observational study of all patients with a FIT submitted Aug 2018 to Jan 2019 in NHS GG&C was performed. Referral to colorectal/gastroenterology and decision to perform colonoscopy were recorded. FIT results were grouped as f-Hb < 10/10-149/150-399/ ≥ 400 µg/g. The MCN cancer registry identified new cases of CRC. Covariables were compared using the χ2 test. Multivariate binary logistic regression identified independent predictors of CRC. RESULTS: A total of 4968 patients were included. Raised FIT correlated with decision to refer (p < 0.001) and scope (p < 0.001). With 23-month median follow-up, 61 patients were diagnosed with CRC. These patients were older (median 69 vs 59 years, cancer and no cancer respectively, p = 0.001), more likely to be male (55.7% vs 42.1%, p = 0.033), and to report rectal bleeding (51.7% vs 36.1%, p = 0.013). FIT (< 10 µg/g 8.2% vs 76.7% and ≥ 400 µg/g 55.7% vs 3.8%, p < 0.001) and anaemia (45.9% vs 19.7%, p < 0.001) were associated with CRC. On multivariate analysis, age (p = 0.023), male sex (p = 0.04), FIT (≥ 400 OR 54.256 (95% CI:20.683-142.325; p < 0.001)), and anaemia (OR 1.956 (1.071-3.574; p = 0.029)) independently predicted CRC. One patient (0.04%) with a negative FIT and normal haemoglobin had CRC. CONCLUSION: GP referral and secondary care investigation patterns were influenced by FIT. The combination of normal Hb and f-Hb excluded CRC in 99.96% of cases, providing excellent reassurance to those prioritising access to endoscopy services.

Longitudinal Changes in CT Body Composition in Patients Undergoing Surgery for Colorectal Cancer and Associations With Peri-Operative Clinicopathological Characteristics.

There is evidence for the direct association between body composition, the magnitude of the systemic inflammatory response, and outcomes in patients with colorectal cancer. Patients with a primary operable disease with and without follow-up CT scans were examined in this study. CT scans were used to define the presence and changes in subcutaneous fat, visceral fat, skeletal muscle mass, and skeletal muscle density (SMD). In total, 804 patients had follow-up scans and 83 patients did not. Furthermore, 783 (97%) patients with follow-up scans and 60 (72%) patients without follow-up scans were alive at 1 year. Patients with follow-up scans were younger (p < 0.001), had a lower American Society of Anaesthesiology Grade (p < 0.01), underwent a laparoscopic surgery (p < 0.05), had a higher BMI (p < 0.05), a higher skeletal muscle index (SMI) (p < 0.01), a higher SMD (p < 0.01), and a better 1-year survival (p < 0.001). Overall only 20% of the patients showed changes in their SMI (n = 161) and an even lower percentage of patients showed relative changes of 10% (n = 82) or more. In conclusion, over the period of ~12 months, a low-skeletal muscle mass was associated with a systemic inflammatory response and was largely maintained following surgical resection.

Postoperative C-reactive protein concentrations to predict infective complications following gastrectomy for cancer.

BACKGROUND AND OBJECTIVES: Gastrectomy for gastric cancer is associated with significant infective postoperative complications. C-reactive protein (CRP) is a useful biomarker in the early detection of infective complications following major abdominal surgery. This single-centre retrospective study aimed to determine the relationship between postoperative CRP levels and development of postoperative infective complications after gastrectomy. METHODS: Daily postoperative CRP levels were analyzed to determine a CRP threshold associated with infective complications. ROC curve analysis was used to determine which postoperative day (POD) gave the optimal cutoff. Multivariate analysis was performed to determine significant factors associated with complications. RESULTS: One hundred and forty-four patients were included. A total of 61 patients (42%) had at least one infective complication. A CRP level of 220 mg/L was associated with the highest AUC (0.765) with a sensitivity of 70% and specificity of 76% (positive predictive value, 67%; negative predictive value, 78%). More patients with a CRP > 220 mg/L on POD 3 developed infective complications (67% vs. 21%, p < 0.001). CONCLUSIONS: A CRP of more than 220 mg/L on POD 3 may be useful to alert clinicians to the increased risk of a postoperative infective complication or enable earlier safe discharge from critical care for those with a lower value.

The inflammatory microenvironment in screen-detected premaligant adenomatous polyps: early results from the integrated technologies for improved polyp surveillance (INCISE) project.

INTRODUCTION: Around 40% of patients who attend colonoscopy following a positive stool screening test have adenomatous polyps. Identifying which patients have a higher propensity for malignant transformation is currently poorly understood. The aim of the present study was to assess whether the type and intensity of inflammatory infiltrate differ between screen-detected adenomas with high-grade dysplasia (HGD) and low-grade dysplasia (LGD). METHODS: A representative sample of 207 polyps from 134 individuals were included from a database of all patients with adenomas detected through the first round of the Scottish Bowel Screening Programme in NHS Greater Glasgow and Clyde (April 2009-April 2011). Inflammatory cell phenotype infiltrate was assessed by immunohistochemistry for CD3+, CD8+, CD45+ and CD68+ in a semi-quantitative manner at 20× resolution. Immune-cell infiltrate was graded as absent, weak, moderate or strong. Patient and polyp characteristics and inflammatory infiltrate were then compared between HGD and LGD polyps. RESULTS: CD3+ infiltrate was significantly higher in HGD polyps compared to LGD polyps (74 vs. 69%; P < 0.05). CD8+ infiltrate was significantly higher in HGD polyps compared to LGD polyps (36 vs. 13%; P < 0.001) whereas CD45+ infiltrate was not significantly different (69 vs. 64%; P = 0.401). There was no significant difference in CD68+ infiltrate (P = 0.540) or total inflammatory cell infiltrate (calculated from CD3+ and CD68+) (P = 0.226). CONCLUSIONS: This study reports an increase in CD3+ and CD8+ infiltrate in HGD colonic adenomas when compared to LGD adenomas. It may therefore have a use in the prognostic stratification and treatment of dysplastic polyps.

Impact of anaemia in oesophago-gastric cancer patients undergoing curative treatment by means of neoadjuvant chemotherapy and surgery.

BACKGROUND: The present study investigated factors associated with pre-neoadjuvant chemotherapy (NAC), and pre-operative anaemia, and examined their impact on outcomes in patients with oesophago-gastric cancer treated with curative intent. METHODS: Patients diagnosed with oesophago-gastric cancer (January 2010 to December 2015) and treated with curative intent by NAC then surgery at a tertiary centre were included. Patients were grouped by the presence of anaemia (haemoglobin <130 mg/L in males and <120 mg/L in females) and into microcytic (MCV <80 fL), normocytic (80-100 fL) and macrocytic (>100 fL) subgroups. Categorical data were analysed by chi-squared test and overall survival by univariate and multivariate Cox regression. RESULTS: 99/295 (34%) patients who received NAC were diagnosed with pre-NAC anaemia, and 157/268 (59%) of patients who subsequently underwent surgery were diagnosed with pre-operative anaemia. Normocytic anaemia was the most common, with 76 (26%) in pre-NAC and 107 (40%) in pre-operative groups. Pre-NAC anaemia was associated with increasing clinical N stage (p = 0.022), higher modified Glasgow Prognostic Score (mGPS) (p = 0.006), and a higher rate of intra-operative transfusion (p = 0.030). Pre-operative anaemia was associated with pre-NAC anaemia (p = 0.004), increasing age (p = 0.026), higher pre-operative mGPS (p = 0.021), and a higher rate of intra-operative transfusion (p = 0.021). Anaemia before NAC and surgery was associated with poorer overall survival in patient following R0 resection, independent of stage (HR 1.26, 95% CI 1.02-1.54, p = 0.030). CONCLUSION: Anaemia was associated with poorer overall survival and greater requirement for intra-operative blood transfusion in oesophago-gastric cancer patients undergoing treatment with curative intent.

The effect of anesthesia on the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colorectal cancer in the context of an enhanced recovery pathway: A prospective cohort study.

ABSTRACT: There are reports that the use of regional anesthesia (RA) may be associated with better perioperative surgical stress response in cancer patients compared with general anesthetics (GA). However, the role of anesthesia on the magnitude of the postoperative systemic inflammatory response (SIR) in colorectal cancer patients, within an enhanced recovery pathway (ERP), is not clear.The aim of the present study was to examine the effect of anesthesia, within an enhanced recovery pathway, on the magnitude of the postoperative SIR in patients undergoing elective surgery for colorectal cancer.Database of 507 patients who underwent elective open or laparoscopic colorectal cancer surgery between 2015 and 2019 at a single center was studied. The anesthetic technique used was categorized into either GA or GA + RA using a prospective proforma. The relationship between each anesthetic technique and perioperative clinicopathological characteristics was examined using binary logistic regression analysis.The majority of patients were male (54%), younger than 65 years (41%), either normal or overweight (64%), and were nonsmokers (47%). Also, the majority of patients underwent open surgery (60%) and received mainly general + regional anesthetic technique (80%). On univariate analysis, GA + RA was associated with a lower day 4 CRP (≤150/>150 mg/L) concentration. On day 4, postoperative CRP was associated with anesthetic technique [odds ratio (OR) 0.58; confidence interval (CI) 0.31-1.07; P = .086], age (OR 0.70; CI 0.50-0.98; P = .043), sex (OR 1.15; CI 0.95-2.52; P = .074), smoking (OR 1.57; CI 1.13-2.19; P = .006), preoperative mGPS (OR 1.55; CI 1.15-2.10; P = .004), and preoperative dexamethasone (OR 0.70; CI 0.47-1.03; P = .072). On multivariate analysis, day 4 postoperative CRP was independently associated with anesthetic technique (OR 0.56; CI 0.32-0.97; P = .039), age (OR 0.74; CI 0.55-0.99; P = .045), smoking (OR 1.58; CI 1.18-2.12; P = .002), preoperative mGPS (OR 1.41; CI 1.08-1.84; P = .012), and preoperative dexamethasone (OR 0.68; CI 0.50-0.92; P = .014).There was a modest but an independent association between RA and a lower magnitude of the postoperative SIR. Future work is warranted with multicenter RCT to precisely clarify the relationship between anesthesia and the magnitude of the postoperative SIR.

Yield of colorectal cancer at colonoscopy according to faecal haemoglobin concentration in symptomatic patients referred from primary care.

AIM: Lower gastrointestinal (GI) symptoms are poor predictors of colorectal cancer (CRC). The aim of this study was to examine the diagnostic yield of colonoscopy by faecal haemoglobin (f-Hb) concentration in symptomatic patients assessed in primary care by faecal immunochemical testing (FIT). METHOD: In three Scottish NHS Boards, FIT kits (HM-JACKarc, Hitachi Chemical Diagnostics Systems Co., Ltd, Tokyo, Japan) were used by general practitioners to guide referrals for patients with lower GI symptoms (laboratory data studied for 12 months from December 2015 onwards in Tayside, 18 months from June 2018 onwards in Fife and 5 months from September 2018 onwards in Greater Glasgow and Clyde). Cases of CRC diagnosed at colonoscopy were ascertained from colonoscopy and pathology records. RESULTS: Four thousand eight hundred and forty one symptomatic patients who underwent colonoscopy after FIT submission were included. Of the 2166 patients (44.7%) with f-Hb <10 µg Hb/g faeces (µg/g), 14 (0.6%) were diagnosed with CRC, with a number needed to scope (NNS) of 155. Of the 2675 patients (55.3%) with f-Hb ≥10 µg/g, 252 were diagnosed with CRC (9.4%) with a NNS of 11. Of the 705 patients with f-Hb ≥400 µg/g, 158 (22.4%) were diagnosed with CRC with a NNS of 5. Over half of those diagnosed with CRC with f-Hb <10 µg/g had coexisting anaemia. CONCLUSION: Symptomatic patients with f-Hb ≥10 µg/g should undergo further investigation for CRC, while higher f-Hb concentrations could be used to triage for urgency during the COVID-19 recovery phase. Patients with f-Hb <10 µg/g and without anaemia are very unlikely to be diagnosed with CRC and the majority need no further investigation.

Staging the Tumor and Staging the Host: Pretreatment Combined Neutrophil Lymphocyte Ratio and Modified Glasgow Prognostic Score Is Associated with Overall Survival in Patients with Esophagogastric Cancers Undergoing Treatment with Curative Intent.

BACKGROUND: This study examined whether an innate systemic inflammatory response (SIR) measured by combination neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) was associated with overall survival (OS) in patients with esophagogastric cancer (EC) undergoing neoadjuvant chemotherapy (NAC) followed by surgery. METHODS: Patients diagnosed with EC, managed with NAC prior to surgery at a regional referral center, between January 2010 and December 2015, were included. The mGPS and NLR were calculated within 12 weeks before NAC. Patients were grouped by combined NLR/mGPS score into three groups of increasing SIR: NLR ≤ 3 (n = 152), NLR > 3 + mGPS = 0 (n = 55), and NLR > 3 + mGPS > 0 (n = 32). Univariable and multivariable Cox regression was used to analyse OS. RESULTS: Overall, 337 NAC patients were included, with 301 (89%) proceeding to surgery and 215 (64%) having R0 resection. There were 203 deaths, with a median follow-up of those alive at censor of 69 months (range 44-114). Higher combined NLR/mGPS score (n = 239) was associated with poorer OS independent of clinical stage and performance status (hazard ratio 1.28, 95% confidence interval 1.02-1.61; p = 0.032), higher rate of progression on NAC (7% vs. 7% vs. 19%; p = 0.003), and lower proportion of eventual resection (80% vs. 84% vs. 53%; p = 0.003). CONCLUSIONS: The combined NLR/mGPS score was associated with OS and initial treatment outcomes in patients undergoing NAC prior to surgery for EC, stratifying survival in addition to clinical staging and performance status. The host SIR may be a useful adjunct to multidisciplinary decision making.

The relationship between 18F-FDG-PETCT-derived tumour metabolic activity, nutritional risk, body composition, systemic inflammation and survival in patients with lung cancer.

The aim of this study was to examine the relationship between PET-CT derived tumour glucose uptake as measured by maximum standard glucose uptake (SUVmax) and total lesion glycolysis (TLG), nutritional risk as measured by the malnutrition universal screening tool (MUST), CT derived body composition as measured by skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD), the systemic inflammatory response as measured by the modified Glasgow prognostic score (mGPS) and the neutrophil to lymphocyte ratio (NLR) and survival in patients with lung cancer, treated with radiotherapy. In a retrospective cohort study, 119 patients were included in final analyses. The majority of patients were over 65 (86%), female (52%), had a performance status (ECOG-PS) of 0 or 1 (57%), were at nutritional risk (57%), were overweight (53%), had visceral obesity (62%), had a normal SMI (51%), had a low SMD (62%) and were systemically inflammed (mGPS 1/2, 51%). An elevated TLG was associated with sex (p < 0.05), TNM stage (p < 0.001), MUST (p < 0.01) and mGPS (p < 0.01). An elevated mGPS was associated with age (p < 0.05), NLR (p < 0.01), MUST (p < 0.01), and TLG (p < 0.01). On univariate survival analysis, TNM stage (p < 0.01), mGPS (p < 0.05), NLR (p < 0.01), MUST (p ≤ 0.001), Low SMD (p < 0.05), SUVmax (p ≤ 0.001) and TLG (p < 0.001) were associated with overall survival. On multivariate survival analysis MUST (HR: 1.49 95%CI 1.12-01.98 p < 0.01) and TLG (HR: 2.02 95%CI 1.34-3.04 p = 0.001) remained independently associated with survival. In conclusion, elevated tumour metabolic activity was associated with more advanced stage, greater nutritional risk, the systemic inflammatory response and poorer survival but not body composition analysis in patients with lung cancer. These results suggest that detrimental body composition is not directly determined by tumour metabolic activity but rather an ongoing systemic inflammatory response.

A comparison of the prognostic value of composite ratios and cumulative scores in patients with operable rectal cancer.

The aim of this study was to directly compare the prognostic value of cumulative scores and composite ratios in patients with operable rectal cancer. Within a single surgical unit preoperative differential blood cell results including neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, as well as CRP (C) and albumin (A) levels were recorded. These results were used to construct a series of composite ratios (NLR, PLR, LMR, CAR) and cumulative scores (NLS, PLS, LMS, NPS, mGPS). The relationship between composite ratios and the cumulative scores and clinicopathological characteristics, cancer specific survival (CSS) and overall survival (OS) were examined. A total of 413 patients were included. When adjusted for TNM stage, surgical approach, time of surgery and margin involvement mGPS (p < 0.05) was associated with CSS. In addition, most composite ratios/scores showed correlations with neoadjuvant therapy (p < 0.001). When a direct comparison between NPS (myeloid) and mGPS (liver) was carried out they showed similar associations with both CSS and OS. Therefore, both composite ratios and cumulative scores have been shown to be prognostic in patients with operable rectal cancer.

The impact of preoperative systemic inflammation on the efficacy of intravenous iron infusion to correct anaemia prior to surgery for colorectal cancer.

AIM: Intravenous iron is increasingly used prior to surgery for colorectal cancer (CRC) to correct iron deficiency anaemia and reduce blood transfusion. Its utility in functional iron deficiency (FID) or anaemia of inflammation is less clear. This observational study examined post-iron infusion changes in haemoglobin (Hb) based on grouping by C-reactive protein (CRP) and ferritin. METHODS: Anaemic (M:Hb < 130 mg/L, F:Hb < 120 mg/L) patients with CRC receiving iron infusion, within a preoperative anaemia detection and correction protocol, at a single centre between 2016 and 2019 were included. Patients were grouped by iron deficiency (ferritin < 30 µg/L and CRP ≤ 5 mg/L, n = 18), FID (ferritin < 30 µg/L and CRP > 5 mg/L, n = 17), anaemia of inflammation (ferritin ≥ 30 µg/L and CRP > 5 mg/L, n = 6), and anaemia of other causes (ferritin ≥ 30 µg/L and CRP ≤ 5 mg/L, n = 6). Median change in Hb and postoperative day (POD) 1 Hb was compared by Kruskal-Wallis test. RESULTS: Iron-deficient patients had the greatest increase in Hb after infusion (24 mg/L), highest POD 1 Hb (108 mg/L), and required no blood transfusions. Patients with FID had the second greatest increase in Hb (15 mg/L) and second highest POD 1 Hb (103 mg/L). Those with anaemia of inflammation had little increase in Hb after infusion (3 mg/L) and lower POD 1 Hb (102 mg/L) than either iron-deficient group. Those without iron deficiency showed a decrease in haemoglobin after infusion (- 5 mg/L) and lowest POD 1 Hb (95 mg/L). CONCLUSIONS: Preoperative intravenous iron is less efficacious in patients with anaemia of inflammation and FID undergoing surgery for CRC, compared with true iron deficiency. Further understanding of the role of perioperative iron infusions is required for maximum gain from therapy.

The relationship between anaesthetic technique, clinicopathological characteristics and the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colon cancer.

BACKGROUND/AIM: The magnitude of the postoperative systemic inflammatory response (SIR) is now recognised to be associated with both short and long-term outcomes in patients undergoing surgery for colon cancer. During such surgery, it is unclear whether the anaesthetic regimens influence the magnitude of the postoperative SIR, independent of other factors. The aim of the present study was to examine the association between anaesthetic agents, clinicopathological characteristics and the magnitude of the postoperative SIR in patients undergoing elective surgery for colon cancer. METHODS: Patients with colon cancer who underwent elective open or laparoscopic surgery between 2008 and 2016 (n = 409) were studied at a single center. The relationship between type of anaesthesia, surgical technique; open (n = 241) versus laparoscopic (n = 168) and clinicopathological characteristics was examined by using chi-square testing. The chi-square test was used to determine which anaesthetic group influences the POD 2 CRP for only patients undergoing elective open colon surgery. RESULTS: The majority of patients were <75 years old, male, normal weight or obese, underwent open surgery and had regional anaesthesia, in particular an epidural approach. There was a significant association between type of anaesthesia and post-operative CRP on day 2 (p <0.001) in patients undergoing open surgery but not laparoscopic surgery. Other factors associated with type of anaesthesia included; year of operation (p <0.01), surgical technique (p <0.001), and preoperative dexamethasone (p <0.01). CONCLUSION: In patients undergoing surgery for elective colon cancer, the type of anaesthesia varied over time. The type of anaesthesia appears to influence the magnitude of the postoperative SIR on post-operative day 2 in open surgery but not laparoscopic surgery. Future work using prospective study design is required to better define this relationship.

Perioperative Blood Transfusion is Associated with Postoperative Systemic Inflammatory Response and Poorer Outcomes Following Surgery for Colorectal Cancer.

BACKGROUND: The present study investigated relationships between perioperative blood transfusion, postoperative systemic inflammatory response, and outcomes following surgery for colorectal cancer. METHODS: Data were recorded for patients (n = 544) undergoing potentially curative, elective surgery for colorectal cancer at a single center between 2012 and 2017. Transfusion history was obtained retrospectively from electronic records. Associations between blood transfusion, postoperative C-reactive protein (CRP), albumin, hemoglobin, complications, cancer-specific survival and overall survival (OS) were assessed using propensity score matching (n =116). RESULTS: Of 544 patients, the majority were male (n =294, 54%), over 65 years of age (n =350, 64%), and with colonic (n =347, 64%) node-negative disease (n =353, 65%). Eighty-six patients (16%) required perioperative blood transfusion. In the unmatched cohort, blood transfusion was associated with higher median postoperative day (POD) 3 CRP {143 [interquartile range (IQR) 96-221 mg/L] vs. 120 (IQR 72-188 mg/L); p = 0.004}, lower median POD 3 albumin [24 (IQR 20-26 g/L) vs. 27 (IQR 24-30 g/L); p < 0.001], more postoperative complications [odds ratio (OR) 3.28, 95% confidence interval (CI) 2.03-5.29] and poorer OS [hazard ratio (HR) 3.18, 95% CI 2.08-4.84]. In the propensity score matched cohort, blood transfusion was similarly associated with higher median POD 3 CRP [130 (IQR 93-196 mg/L) vs. 113 (IQR 66-173 mg/L); p = 0.046], lower median POD 3 albumin [24 (IQR 20-26 g/L) vs. 26 (IQR 24-30 g/L); p < 0.001], more postoperative complications (OR 2.91, 95% CI 1.36-6.20) and poorer OS (HR 2.38, 95% CI 0.99-5.73). CONCLUSIONS: Perioperative blood transfusion was associated with postoperative inflammation, complications, and poorer survival in patients undergoing colorectal cancer surgery, with and without propensity score techniques.

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.