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.

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.

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.

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.

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.

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.

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.

The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer.

Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A cohort of 150 patients with stage I-III CRC were utilised to assess tumour cell expression of MCT-1, MCT-2, LDH-1 and LDH-5 by immunohistochemistry. Expression levels were dichotomised and associations with tumour factors, the tumour microenvironment and survival analysed. Nuclear LDH-5 associates with poor prognosis (HR 1.68 95% CI 0.99-2.84, p = 0.050) and trends toward increased tumour stroma percentage (TSP, p = 0.125). Cytoplasmic MCT-2 also trends toward increased TSP (p = 0.081). When combined into a single score; nuclear LDH-5 + TSP significantly associated with decreased survival independent of stage (HR 2.61 95% CI 1.27-5.35, p = 0.009), increased tumour budding (p = 0.002) and decreased stromal T-lymphocytes (p = 0.014). Similarly, cytoplasmic MCT-2 + TSP significantly associated with decreased survival (HR 2.32 95% CI 1.31-4.11, p = 0.003), decreased necrosis (p = 0.039), and increased tumour budding (p = 0.004). The present study reports that the combination of TSP and nuclear LDH-5 was significantly associated with survival, increased tumour budding, and decreased stromal T-lymphocytes. This supports the hypothesis that increased stromal invasion promotes tumour progression via modulation of tumour metabolism. Moreover, MCT-2 and LDH-5 may provide promising therapeutic targets for patients with stromal-rich CRC.

Regression Correction Equation to Adjust Serum Iron and Ferritin Concentrations Based on C-Reactive Protein and Albumin in Patients Receiving Primary and Secondary Care.

BACKGROUND: Systemic inflammation, even at low levels, can greatly interfere with measures of iron status, making diagnosis of iron deficiency difficult. The objective of the present study was to create linear regression correction equations to adjust serum ferritin and iron concentrations based on measurements of the acute-phase proteins C-reactive protein (CRP) and albumin. METHODS: Data from a cohort (1) of patients (n = 7226) in primary and secondary care who had serum ferritin, iron, CRP, and albumin measured at the same time point were examined. Linear regression coefficients were calculated for CRP and albumin with serum iron and ferritin as the outcome variables. Patients with ferritin <15 µg/L or serum iron <10 µmol/L were categorized as iron deficient. The equation was then applied to a cohort (2) of patients with colorectal cancer who had ferritin and iron measured preoperatively ( n = 356). RESULTS: In cohort 1 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (7% and 55%), adjusted based on CRP alone (13% and 26%), adjusted based on albumin alone (11% and 37%), and adjusted based on both CRP and albumin (24% and 15%) values were compared (both P < 0.001). In cohort 2 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (28% and 66%), adjusted based on CRP alone (39% and 57%), adjusted based on albumin alone (39% and 59%), and adjusted based on both CRP and albumin (46% and 44%) values were compared (P < 0.001 and P < 0.004). CONCLUSIONS: In both cohorts the greatest increase in the proportion of patients meeting definitions of iron deficiency was found when adjustment was made for both CRP and albumin together. Even low levels of inflammation had a significant effect on serum iron and ferritin values.

Normocytic anaemia is associated with systemic inflammation and poorer survival in patients with colorectal cancer treated with curative intent.

BACKGROUND: The present study aimed to characterise the prevalence and prognostic impact of normocytic anaemia in patients undergoing curative treatment for colorectal cancer. METHODS: All individuals invited to the first round of bowel cancer screening, diagnosed with colorectal cancer and treated with curative intent from April 2009 to March 2011 in a single health board were included. The modified Glasgow prognostic score (mGPS) was used to quantify preoperative systemic inflammation. Patients were grouped as having microcytic anaemia (Hb < 130 mg/L males, < 120 mg/L females and MCV < 80 fL), normocytic anaemia (Hb < 130 mg/L males, < 120 mg/L females and MCV 80-100 fL), or neither. RESULTS: Of 395,097 patients invited to screening during the study period, 872 were diagnosed with colorectal cancer. Seven hundred seventy-seven patients had FBC measured at diagnosis, of which 78 (10%) had microcytic anaemia, and 180 (23%) normocytic anaemia. On multivariate binary logistic regression, microcytic anaemia was associated with T stage (OR 1.92, 95% CI 1.26-2.91, p = 0.002) and mGPS (OR 1.57, 95% CI 1.10-2.24, p = 0.013), while normocytic anaemia was associated with colonic tumours (OR = 2.51, 95% CI 1.10-4.01, p = 0.025), T stage (OR 1.38, 95% CI 1.05-1.81, p = 0.022), and mGPS (OR 1.52, 95% CI 1.12-2.05, p = 0.007). On univariate Cox regression, there was no significant association between microcytic anaemia and cancer specific survival (CSS) (p = 0.969). Normocytic anaemia was significantly associated with poorer CSS (HR 1.55, 95% CI 1.13-2.12, p = 0.007). CONCLUSIONS: Normocytic anaemia was associated with systemic inflammation and poorer CSS. Inflammation may drive both anaemia and disease recurrence in these patients, and targeting this process may improve both.

Dropped gallstones causing abdominal wall abscess and pleural empyema: a case series.

INTRODUCTION: Dropped gallstones are gallstones lost in the abdominal cavity during cholecystectomy. They are a rare occurrence and often cause minimal long-term issues. However, it is recognised that dropped stones can cause intra- or extra-abdominal sepsis. We present three cases below which highlight this. CASES: All three cases describe patients presenting for laparoscopic cholecystectomy, Cases 1 and 2 post-gallstone pancreatitis and Case 3 for gallbladder stones. Cases 1 and 3 presented nine months and five years post-operatively, respectively, with flank abscess. Both received CT scans, with incision and drainage performed to remove gallstone. Case 2 presented six weeks post-operatively with cough and breathlessness. CT scan showed pleural effusion with communication to subphrenic collection. Pus and gallstone fragments were drained. CONCLUSION: The above cases highlight that despite the majority of patients remaining asymptomatic, dropped gallstones should be considered amongst the differential in patients presenting with intra- or extra-abdominal abscess post-cholecystectomy, with timely intervention key to management.

The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer.

BACKGROUND: There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer. METHODS: Clinicopathological characteristics were extracted from a prospective database. MMR and BRAF status was determined using immunohistochemistry. The tumour microenvironment was assessed using routine H&E pathological sections. SIR was assessed using modified Glasgow Prognostic Score (mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and lymphocyte:monocyte ratio (LMR). RESULTS: Overall, 972 patients were included. The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right-sided tumour location was associated with older age (P=0.001), deficient MMR (P=0.005), higher T stage (P<0.001), poor tumour differentiation (P<0.001), venous invasion (P=0.021), and high CD3+ within cancer cell nests (P=0.048). Right-sided location was consistently associated with a high SIR, mGPS (P<0.001) and NPS (P<0.001). There was no relationship between tumour location, adjuvant chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275 patients who received adjuvant chemotherapy, right-sided location was not associated with the MMR status (P=0.509) but was associated with higher T stage (P=0.001), venous invasion (P=0.036), CD3+ at the invasive margin (P=0.033) and CD3+ within cancer nests (P=0.012). There was no relationship between tumour location, SIR or CSS in the adjuvant group. CONCLUSIONS: Right-sided tumour location was associated with an elevated tumour lymphocytic infiltrate and an elevated SIR. There was no association between tumour location and survival in the non-adjuvant or adjuvant setting in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer.

The prognostic value of systemic inflammation in patients undergoing surgery for colon cancer: comparison of composite ratios and cumulative scores.

INTRODUCTION: The systemic inflammatory response has been proven to have a prognostic value. There are two methods of assessing the systemic inflammatory response composite ratios (R) and cumulative scores (S). The aim of this study was to compare the prognostic value of ratios and scores in patients undergoing surgery for colon cancer. METHODS: Patients were identified prospectively in a single surgical unit. Preoperative neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, CRP (C) and albumin (A) levels were recorded. The relationship between composite ratios neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein albumin ratio (CAR) and the cumulative scores neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil- platelet score (NPS), modified Glasgow prognostic score (mGPS) and clinicopathological characteristics, cancer-specific survival (CSS) and overall survival (OS), were examined. RESULTS: A total of 801 patients were examined. When adjusted for tumour node metastasis (TNM) stage, NLR >5 (p < 0.001), NLS (p < 0.01), PLS (p < 0.001), LMR <2.4 (p < 0.001), LMS (p < 0.001), NPS (p < 0.001), CAR >0.22 (p < 0.001) and mGPS (p < 0.001) were significantly associated with CSS. In patients undergoing elective surgery (n = 689), the majority of the composite ratios/scores correlated with age (p < 0.01), BMI (p < 0.01), T stage (p < 0.01), venous invasion (p < 0.01) and peritoneal involvement (p < 0.01). When NPS (myeloid) and mGPS (liver) were directly compared, their relationship with CSS and OS was similar. CONCLUSIONS: Both composite ratios and cumulative scores had prognostic value, independent of TNM stage, in patients with colon cancer. However, cumulative scores, based on normal reference ranges, are simpler and more consistent for clinical use.

The Impact of Preoperative Dexamethasone on the Magnitude of the Postoperative Systemic Inflammatory Response and Complications Following Surgery for Colorectal Cancer.

BACKGROUND: The magnitude of the postoperative systemic inflammatory response (SIR), as evidenced by C-reactive protein (CRP), is associated with both short- and long-term outcomes following surgery for colorectal cancer. The present study examined the impact of preoperative dexamethasone on the postoperative SIR and complications following elective surgery for colorectal cancer. METHODS: Patients who underwent elective surgery, with curative intent, for colorectal cancer at a single center between 2008 and 2016 were included (n = 556) in this study. Data on the use of preoperative dexamethasone were obtained from anesthetic records, and its impact on CRP on postoperative days (PODs) 3 and 4, as well as postoperative complications, was assessed using propensity score matching (n = 276). RESULTS: In the propensity score-matched cohort, preoperative dexamethasone was associated with fewer patients exceeding the established CRP threshold of 150 mg/L on POD 3 (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.26-0.70, p < 0.001) and fewer postoperative complications (OR 0.53, 95% CI 0.33-0.86, p = 0.009). Similar results for both POD 3 CRP and complications were observed when using propensity score-adjusted regression (OR 0.40, 95% CI 0.28-0.57 and OR 0.57, 95% CI 0.41-0.80, respectively) and propensity score stratification (OR 0.41, 95% CI 0.25-0.57 and OR 0.53, 95% CI 0.33-0.86, respectively). CONCLUSIONS: Preoperative dexamethasone was associated with a lower postoperative SIR and fewer complications following elective surgery for colorectal cancer.

A Postoperative Systemic Inflammation Score Predicts Short- and Long-Term Outcomes in Patients Undergoing Surgery for Colorectal Cancer.

BACKGROUND: Following surgery, a significant proportion of patients develop postoperative complications that are associated with poorer long-term survival. Stereotypical markers of the systemic inflammatory response (SIR) have been shown to identify patients at increased risk of developing such complications. The aim of the present study was to examine the prognostic value of a postoperative systemic inflammation-based score in patients undergoing potentially curative surgery for colorectal cancer. METHODS: Patients with histologically proven colorectal cancer undergoing resection between 1999 and 2013 (n = 813) were grouped into two cohorts-a retrospective test cohort (n = 402) and a prospective validation cohort (n = 411). Patients were assessed for postoperative complications and had routine blood samples taken daily. The relationship between markers of the postoperative SIR and survival was examined using Cox regression analysis. RESULTS: In the test cohort, 87 patients developed an infective complication, while in the validation cohort, 106 patients developed an infective complication. In both cohorts, the postoperative SIR (C-reactive protein and albumin thresholds of >150 mg/L and <25 g/L, respectively) were associated with the development of infective complications (all p < 0.01). Using these thresholds, a scoring system [postoperative Glasgow prognostic score (poGPS)] was created, and on days 3 and 4 was associated with an incremental increase in the infective complication rate (all p < 0.001) and complication severity (p < 0.001). In the overall cohort, there were 175 cancer and 139 non-cancer deaths. The poGPS was also significantly associated with overall survival (p < 0.05). CONCLUSIONS: The postoperative SIR, evidenced by the poGPS, was associated with increased complication rates and severity and a reduction in survival.

Clinicopathological Determinants of an Elevated Systemic Inflammatory Response Following Elective Potentially Curative Resection for Colorectal Cancer.

INTRODUCTION: The postoperative systemic inflammatory response (SIR) is related to both long- and short-term outcomes following surgery for colorectal cancer. However, it is not clear which clinicopathological factors are associated with the magnitude of the postoperative SIR. The present study was designed to determine the clinicopathological determinants of the postoperative systemic inflammatory response following colorectal cancer resection. METHODS: Patients with a histologically proven diagnosis of colorectal cancer who underwent elective, potentially curative resection during a period from 1999 to 2013 were included in the study (n = 752). Clinicopathological data and the postoperative SIR, as evidenced by postoperative Glasgow Prognostic Score (poGPS), were recorded in a prospectively maintained database. RESULTS: The majority of patients were aged 65 years or older, male, were overweight or obese, and had an open resection. After adjustment for year of operation, a high day 3 poGPS was independently associated with American Society of Anesthesiologists (ASA) grade (hazard ratio [HR] 1.96; confidence interval [CI] 1.25-3.09; p = 0.003), body mass index (BMI) (HR 1.60; CI 1.07-2.38; p = 0.001), mGPS (HR 2.03; CI 1.35-3.03; p = 0.001), and tumour site (HR 2.99; CI 1.56-5.71; p < 0.001). After adjustment for year of operation, a high day 4 poGPS was independently associated with ASA grade (HR 1.65; CI 1.06-2.57; p = 0.028), mGPS (HR 1.81; CI 1.22-2.68; p = 0.003), NLR (HR 0.50; CI 0.26-0.95; p = 0.034), and tumour site (HR 2.90; CI 1.49-5.65; p = 0.002). CONCLUSIONS: ASA grade, BMI, mGPS, and tumour site were consistently associated with the magnitude of the postoperative systemic inflammatory response, evidenced by a high poGPS on days 3 and 4, in patients undergoing elective potentially curative resection for colorectal cancer.

The Pretreatment Systemic Inflammatory Response is an Important Determinant of Poor Pathologic Response for Patients Undergoing Neoadjuvant Therapy for Rectal Cancer.

BACKGROUND: Not all patients respond equally to neoadjuvant chemoradiotherapy (nCRT), with subsequent effects on survival. The systemic inflammatory response has been shown to predict long-term outcomes in colorectal cancer. The current study examined the association between systemic inflammation and nCRT in patients with rectal cancer. METHODS: Between 1999 and 2010, patients who underwent nCRT were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow prognostic score (mGPS), and differential white cell counts were obtained before and after nCRT. The Rödel scoring system measured pathologic tumor regression, and magnetic resonance imaging and computed tomography determined radiologic staging. RESULTS: The study included 79 patients. Of these patients, 37% were radiologically downstaged, and 44% were categorized as showing a good pathologic response (Rödel scores 3 and 4). As a validated measure of the systemic inflammatory response, mGPS (P = 0.022) was associated with a poor pathologic response to nCRT. A radiologic response was associated with a good pathologic response to treatment (P = 0.003). A binary logistic regression model identified mGPS (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.07-0.96; P = 0.043) and radiologic response (OR 0.43; 95% CI 0.18-0.99; P = 0.048) as strong independent predictors of a pathologic response to treatment. CONCLUSION: The current study showed that a systemic inflammatory response before nCRT is associated with a poor pathologic response. Further study in a prospective controlled trial setting is warranted.

Postoperative Systemic Inflammatory Response, Complication Severity, and Survival Following Surgery for Colorectal Cancer.

BACKGROUND: This study examined the relationship between the magnitude of the postoperative systemic inflammatory response (SIR), the severity of complications, and long-term outcomes following surgery for colorectal cancer. METHODS: Data were recorded prospectively for patients undergoing potentially curative surgery for colorectal cancer in a single centre between 2008 and 2013. The magnitude of the SIR was measured using C-reactive protein (CRP). Complications were classified by Clavien-Dindo grade. The impact on disease specific and overall survival was assessed using univariate and multivariate Cox regression. RESULTS: Of 377 patients included, the majority were male (55 %), older than age 65 years (68 %), with colonic (63 %) and node-negative disease (66 %). A total of 138 patients (37 %) had a complication, of which 26 (6 %) were Clavien-Dindo grade 3 or 4 severity. Complication severity was significantly associated with the established CRP thresholds of 150 mg/L on postoperative day (POD) 3 (p < 0.001) and POD 4 (p < 0.001). Median follow-up was 42 months with disease-specific survival 86 % and overall survival 78 %. On univariate analysis, complication severity [hazard ratio (HR) 1.66, 95 % confidence interval (CI) 1.13-2.43, p = 0.009], and POD 4 CRP > 150 mg/L (HR 2.53, 95 % CI 1.43-4.48, p = 0.001) were associated with disease-specific survival. On multivariate survival analysis, POD 4 CRP > 150 mg/L (HR 2.00, 95 % CI 1.12-3.59, p = 0.020), but not complication severity, was significantly associated with disease-specific survival independent of TNM stage (HR 2.46, 95 % CI 1.52-4.12, p < 0.001). CONCLUSIONS: The magnitude of the postoperative SIR, evidenced by CRP, was significantly associated with long-term outcomes following surgery for colorectal cancer, independent of complications and stage.