Prognostic significance of competition ratios in surgical specialty training selection.

BACKGROUND: A competition ratio (CR) indicates the ratio of total applications for a training post when compared with numbers of specialty posts available. This study aimed to evaluate CRs' influence on National Training Number (NTN) selection in a single UK Statutory Education Body. METHODS: Consecutive core surgical trainees numbering 154 (105 men, 49 women; median years since graduation: four) were studied over a 6-year period. Annual specialty specific CRs were obtained from Health Education England's website, and primary outcome measure was UK NTN appointment. RESULTS: Overall NTN appointment was 45.5%. Median CR was 2.36; range Oral & Maxillofacial Surgery 0.70 (2020) to Neurosurgery 22.0 (2020). Multivariable analysis revealed that NTN success was associated with: CR (OR 0.46, p=0.003), a single scientific publication (OR 6.25, p=0.001), cohort year (2019, OR 12.65, p=0.003) and Universal Annual Review of Competence Progression Outcome 1 (OR 45.24, p<0.001). CRs predicted NTN appointment with a Youden index defined critical ratio of 4.42; 28.6% (n=8) versus 49.2% (n=62), p=0.018. CONCLUSION: CRs displayed 30-fold variation, with CRs below 4.42 associated with twofold better NTN promotion, but strong clinical competence and academic reach again emerged as the principal drivers of career advancement.

The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer.

BACKGROUND: The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy. METHODS: Two cohorts were utilised; 862 TNM I-III CRC validation cohort, and 2912 TNM II-III CRC adjuvant chemotherapy cohort (TransSCOT). Primary endpoints were disease-free survival (DFS) and relapse-free survival (RFS). Exploratory endpoint was adjuvant chemotherapy interaction. RESULTS: GMS independently associated with DFS (p = 0.001) and RFS (p < 0.001). GMS significantly stratified RFS for both low risk (GMS 0 v GMS 2: HR 3.24 95% CI 1.85-5.68, p < 0.001) and high-risk disease (GMS 0 v GMS 2: HR 2.18 95% CI 1.39-3.41, p = 0.001). In TransSCOT, chemotherapy type (pinteraction = 0.013), but not duration (p = 0.64) was dependent on GMS. Furthermore, GMS 0 significantly associated with improved DFS in patients receiving FOLFOX compared with CAPOX (HR 2.23 95% CI 1.19-4.16, p = 0.012). CONCLUSIONS: This study validates the GMS as a prognostic tool for patients with stage I-III colorectal cancer, independent of TNM, with the ability to stratify both low- and high-risk disease. Furthermore, GMS 0 could be employed to identify a subset of patients that benefit from FOLFOX over CAPOX.

Prognostic significance of serum inflammatory markers in esophageal cancer.

BACKGROUND: The aim of this study was to assess the relative prognostic value of biomarkers to measure the systemic inflammatory response (SIR) and potentially improve prognostic modeling in patients undergoing potentially curative surgery for esophageal adenocarcinoma (EC). METHODS: Consecutive 330 patients undergoing surgery for EC between 2004 and 2018 within a regional UK cancer network were identified. Serum measurements of haemoglobin, C-reactive protein, albumin, modified Glasgow Prognostic Score (mGPS), and differential neutrophil to lymphocyte ratio (NLR) were obtained before surgery, and correlated with histopathological factors and outcomes. Primary outcome measures were disease-free (DFS) and overall survival (OS). RESULTS: Of 330 OC patients, 294 underwent potentially curative esophagectomy. Univariable DFS analysis revealed pT, pN, pTNM stage (all p < 0.001), poor differentiation (p = 0.001), vascular invasion (p < 0.001), R1 status (p < 0.001), perioperative chemotherapy (p = 0.009), CRP (p = 0.010), mGPS (p = 0.011), and NLR (p < 0.001), were all associated with poor survival. Multivariable Cox regression analysis of DFS revealed only NLR [Hazard Ratio (HR) 3.63, 95% Confidence Interval (CI) 2.11-6.24, p < 0.001] retained significance. Multivariable Cox regression analysis of OS revealed similar findings: NLR [HR 2.66, (95% CI 1.58-4.50), p < 0.001]. CONCLUSION: NLR is an important SIR prognostic biomarker associated with DFS and OS in EC.

Targeting Wnt Signaling for the Treatment of Gastric Cancer.

The Wnt signaling pathway is evolutionarily conserved, regulating both embryonic development and maintaining adult tissue homeostasis. Wnt signaling controls several fundamental cell functions, including proliferation, differentiation, migration, and stemness. It therefore plays an important role in the epithelial homeostasis and regeneration of the gastrointestinal tract. Often, both hypo- or hyper-activation of the pathway due to genetic, epigenetic, or receptor/ligand alterations are seen in many solid cancers, such as breast, colorectal, gastric, and prostate. Gastric cancer (GC) is the fourth commonest cause of cancer worldwide and is the second leading cause of cancer-related death annually. Although the number of new diagnoses has declined over recent decades, prognosis remains poor, with only 15% surviving to five years. Geographical differences in clinicopathological features are also apparent, with epidemiological and genetic studies revealing GC to be a highly heterogeneous disease with phenotypic diversity as a result of etiological factors. The molecular heterogeneity associated with GC dictates that a single 'one size fits all' approach to management is unlikely to be successful. Wnt pathway dysregulation has been observed in approximately 50% of GC tumors and may offer a novel therapeutic target for patients who would otherwise have a poor outcome. This mini review will highlight some recent discoveries involving Wnt signaling in GC.

Relative Value of Adapted Novel Bibliometrics in Evaluating Surgical Academic Impact and Reach.

BACKGROUND: The Hirsch index, often used to assess research impact, suffers from questionable validity within the context of General Surgery, and consequently adapted bibliometrics and altmetrics have emerged, including the r-index, m-index, g-index and i10-index. This study aimed to assess the relative value of these novel bibliometrics in a single UK Deanery General Surgical Consultant cohort. METHOD: Five indices (h, r, m, g and i10) and altmetric scores (AS) were calculated for 151 general surgical consultants in a UK Deanery. Indices and AS were calculated from publication data via the Scopus search engine with assessment of construct validity and reliability. RESULTS: The median number of publications, h-index, r-index, m-index, g-index and i10-index were 13 (range 0-389), 5 (range 0-63), 5.2 (range 0-64.8), 0.33 (range 0-1.5), 10 (range 0-125) and 4 (range 0-245), respectively. Correlation coefficients of r-index, m-index, g-index and i10-index with h-index were 0.913 (p < 0.001), 0.716 (p < 0.001), 0.961 (p < 0.001) and 0.939 (p < 0.001), respectively. Significant variance was observed when the cohort was ranked by individual bibliometric measures; the median ranking shifts were: r-index - 2 (- 46 to + 23); m-index - 6.5 (- 53 to + 22); g-index - 0.5 (- 24 to + 13); and i10-index 0 (- 8 to + 11), respectively (p < 0.001). The median altmetric score and AS index were 0 (range 0-225.5) and 1 (range 0-10), respectively; AS index correlated strongly with h-index (correlation coefficient 0.390, p < 0.001). CONCLUSIONS: Adapted bibliometric indices appear to be equally valid measures of evaluating academic productivity, impact and reach.

Mode of presentation rather than the 'weekend effect' is a major determinant of in-hospital mortality.

BACKGROUND: The influence of patient demographics and mode of admission on the 'weekend effect' remains unclear. This study examins the relationship between day of admission, patient demographics, mode of presentation and survival. METHODS: Hospital admissions over a three-year period were studied. Patients with an inpatient stay less than 24 h and those who were discharged from the emergency department were excluded. In-hospital mortality was correlated with day of admission, age, gender and mode of presentation in a binary logistical regression analysis. RESULTS: There were 448,827 admissions, of which 350,648 (85.7%) occurred during a weekday. 256,777 (62.7%) were emergency presentations, which was closely related to a weekend admission (92.3% vs 57.8%, p < 0.001). There were 8099 deaths of which 6336 (78.2%) related to a weekday admission and 1736 (21.4%) related a weekend admission. Mortality for elective admissions was 78 (0.05%) compared to 8021 (3.12%), p < 0.001 in emergency admissions. Univariable regression analysis revealed a weekend admission (Odds Ratio (OR) 1.68 (95% confidence interval (CI) 1.60-1.78, p < 0.001) and emergency presentation (OR 63.02 (95%CI 50.42-78.77), p < 0.011) were associated with weekend mortality. On multivariable analysis the OR for weekend admission reduced to 1.07 (95%CI 1.01-1.13), p = 0.013 and the OR for emergency presentation increased to 76.68 (95%CI 61.40-96.00), p < 0.001. CONCLUSION: This study highlights that higher weekend mortality rates are a consequence of a lower proportion of elective admissions. Extending the working week to seven days might reduce weekend mortality without reducing the total number of deaths.

Altmetric Versus Bibliometric Perspective Regarding Publication Impact and Force.

BACKGROUND: Bibliometric and Altmetric analyses highlight key publications, which have been considered to be the most influential in their field. The hypothesis was that highly cited articles would correlate positively with levels of evidence and Altmetric scores (AS) and rank. METHODS: Surgery as a search term was entered into Thomson Reuter's Web of Science database to identify all English-language full articles. The 100 most cited articles were analysed by topic, journal, author, year, institution, and AS. RESULTS: By bibliometric criteria, eligible articles numbered 286,122 and the median (range) citation number was 574 (446-5746). The most cited article (Dindo et al.) classified surgical complications by severity score (5746 citations). Annals of Surgery published most articles and received most citations (26,457). The country and year with most publications were the USA (n = 50) and 1999 (n = 11). By Altmetric criteria, the article with the highest AS was by Bigelow et al. (AS = 53, hypothermia's role in cardiac surgery); Annals of Surgery published most articles, and the country and year with most publications were USA (n = 4) and 2007 (n = 3). Level-1-evidence articles numbered 13, but no correlation was found between evidence level and citation number (SCC 0.094, p = 0.352) or AS (SCC = 0.149, p = 0.244). Median AS was 0 (0-53), and in articles published after the year 2000, AS was associated with citation number (r = 0.461, p = 0.001) and citation rate index (r = 0.455, p = 0.002). AS was not associated with journal impact factor (r = 0.160, p = 0.118). CONCLUSION: Bibliometric and Altmetric analyses provide important but different perspectives regarding article impact, which are unrelated to evidence level.

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.

Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment.

BACKGROUND: Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is associated with a conspicuous local immune infiltrate; however, its relationship with systemic inflammatory responses remains to be determined. The present study aims to examine the relationships and prognostic value of assessment of the local and systemic environment in the context of MMR status in patients with CRC. METHODS: The relationship between MMR status, determined using immunohistochemistry, and the local inflammatory cell infiltrate, differential white cell count, neutrophil : platelet score (NPS), neutrophil : lymphocyte ratio and modified Glasgow Prognostic Score (mGPS), and cancer-specific survival was examined in 228 patients undergoing resection of stage I-III CRC. RESULTS: Thirty-five patients (15%) had dMMR CRC. Mismatch repair deficiency was associated with a higher density of CD3(+), CD8(+) and CD45R0(+) T lymphocytes within the cancer cell nests and an elevated mGPS (mGPS2: 23% vs 9%, P=0.007) and NPS (NPS2: 19% vs 3%, P=0.001). CD3(+) density (P<0.001), mGPS (P=0.01) and NPS (P=0.042) were associated with survival independent of MMR status (P=0.367) and stratified 5-year survival of patients with MMR-competent CRC from 94% to 67%, 83% to 46% and 78% to 60% respectively. CONCLUSIONS: Mismatch repair deficiency was associated with local and systemic environments, and in comparison with their assessment, dMMR had relatively poor prognostic value in patients with primary operable CRC. In addition to MMR status, local and systemic inflammatory responses should be assessed in these patients.

Long-Term Follow-Up of Patients Undergoing Resection of TNM Stage I Colorectal Cancer: An Analysis of Tumour and Host Determinants of Outcome.

BACKGROUND: Screening for colorectal cancer improves cancer-specific survival (CSS) through the detection of early-stage disease; however, its impact on overall survival (OS) is unclear. The present study examined tumour and host determinants of outcome in TNM Stage I disease. METHODS: All patients with pathologically confirmed TNM Stage I disease across 4 hospitals in the North of Glasgow between 2000 and 2008 were included. The preoperative modified Glasgow Prognostic Score (mGPS) was used as a marker of the host systemic inflammatory response (SIR). RESULTS: There were 191 patients identified, 105 (55 %) were males, 91 (48 %) were over the age of 75 years and 7 (4 %) patients underwent an emergency operation. In those with a preoperative CRP result (n = 150), 35 (24 %) patients had evidence of an elevated mGPS. Median follow-up of survivors was 116 months (minimum 72 months) during which 88 (46 %) patients died; 7 (8 %) had postoperative deaths, 15 (17 %) had cancer-related deaths and 66 (75 %) had non-cancer-related deaths. 5-year CSS was 95 % and OS was 76 %. On univariate analysis, advancing age (p < 0.001), emergency presentation (p = 0.008), and an elevated mGPS (p = 0.012) were associated with reduced OS. On multivariate analysis, only age (HR = 3.611, 95 % CI 2.049-6.365, p < 0.001) and the presence of an elevated mGPS (HR = 2.173, 95 % CI 1.204-3.921, p = 0.010) retained significance. CONCLUSIONS: In patients undergoing resection for TNM Stage I colorectal cancer, an elevated mGPS was an objective independent marker of poorer OS. These patients may benefit from a targeted intervention.

Undergraduate medical textbooks do not provide adequate information on intravenous fluid therapy: a systematic survey and suggestions for improvement.

BACKGROUND: Inappropriate prescribing of intravenous (IV) fluid, particularly 0.9% sodium chloride, causes post-operative complications. Fluid prescription is often left to junior medical staff and is frequently poorly managed. One reason for poor intravenous fluid prescribing practices could be inadequate coverage of this topic in the textbooks that are used. METHODS: We formulated a comprehensive set of topics, related to important common clinical situations involving IV fluid therapy, (routine fluid replacement, fluid loss, fluids overload) to assess the adequacy of textbooks in common use. We assessed 29 medical textbooks widely available to students in the UK, scoring the presence of information provided by each book on each of the topics. The scores indicated how fully the topics were considered: not at all, partly, and adequately. No attempt was made to judge the quality of the information, because there is no consensus on these topics. RESULTS: The maximum score that a book could achieve was 52. Three of the topics we chose were not considered by any of the books. Discounting these topics as "too esoteric", the maximum possible score became 46. One textbook gained a score of 45, but the general score was poor (median 11, quartiles 4, 21). In particular, coverage of routine postoperative management was inadequate. CONCLUSIONS: Textbooks for undergraduates cover the topic of intravenous therapy badly, which may partly explain the poor knowledge and performance of junior doctors in this important field. Systematic revision of current textbooks might improve knowledge and practice by junior doctors. Careful definition of the remit and content of textbooks should be applied more widely to ensure quality and "fitness for purpose", and avoid omission of vital knowledge.

A case of septicaemic anthrax in an intravenous drug user.

BACKGROUND: In 2000, Ringertz et al described the first case of systemic anthrax caused by injecting heroin contaminated with anthrax. In 2008, there were 574 drug related deaths in Scotland, of which 336 were associated with heroin and or morphine. We report a rare case of septicaemic anthrax caused by injecting heroin contaminated with anthrax in Scotland. CASE PRESENTATION: A 32 year old intravenous drug user (IVDU), presented with a 12 hour history of increasing purulent discharge from a chronic sinus in his left groin. He had a tachycardia, pyrexia, leukocytosis and an elevated C-reactive protein (CRP). He was treated with Vancomycin, Clindamycin, Ciprofloxacin, Gentamicin and Metronidazole. Blood cultures grew Bacillus anthracis within 24 hours of presentation. He had a computed tomography (CT) scan and magnetic resonance imagining (MRI) of his abdomen, pelvis and thighs performed. These showed inflammatory change relating to the iliopsoas and an area of necrosis in the adductor magnus.He underwent an exploration of his left thigh. This revealed chronically indurated subcutaneous tissues with no evidence of a collection or necrotic muscle. Treatment with Vancomycin, Ciprofloxacin and Clindamycin continued for 14 days. Negative Pressure Wound Therapy (NPWT) device was applied utilising the Venturi™ wound sealing kit. Following 4 weeks of treatment, the wound dimensions had reduced by 77%. CONCLUSIONS: Although systemic anthrax infection is rare, it should be considered when faced with severe cutaneous infection in IVDU patients. This case shows that patients with significant bacteraemia may present with no signs of haemodynamic compromise. Prompt recognition and treatment with high dose IV antimicrobial therapy increases the likelihood of survival. The use of simple wound therapy adjuncts such as NPWT can give excellent wound healing results.

Economic cost-utility analysis of stage-directed gastric cancer treatment.

BACKGROUND: Gastric cancer (GC) treatment levies substantial financial burden on health services. Potentially curative surgery with or without chemotherapy is offered to patients with locoregional disease. This study aimed to examine treatment costs related to life-years gained in patients having potentially curative treatment (gastrectomy) and those receiving best supportive care (BSC). METHODS: Some 398 consecutive patients with GC were classified according to treatment modality (116 BSC, 282 gastrectomy). Cost calculations for 1 year's treatment from referral were made according to network diagnostic, staging and treatment algorithms. Primary outcome was overall survival (OS). RESULTS: GC median survival after BSC was 8 months, costing €5413, compared with gastrectomy median survival of 34 months, costing €22 753 for 1 year's treatment: cost per life-year gained €9319. Cost incurred for stage I GC was €22 434, stage II €23 498, stage III €22 445, and stage IV €22 032. Based on these values, the cost per quality adjusted life-year (QALY) for BSC for stage I GC was -€8335 stage II -€8952, stage III -€11 317, and stage IV -€25 669. CONCLUSION: Potentially curative treatment that included gastrectomy improved OS four-fold compared with BSC and was cost-effective at national thresholds of readiness to pay per QALY.

Biosensors, Biomarkers and Biometrics: a Bootcamp Perspective.

Introduction: Competitive physical performance is routinely monitored by wearable technology (biosensors), yet professional healthcare is not, despite high prevalence of trainee stress and burnout, notwithstanding the corresponding risk to patient safety. This study aimed to document the physiological stress response of UK Core Surgical Trainees (CSTs) during simulation training. Methods: CSTs (n=20, 10 male) were fitted with Vital Scout Wellness Monitors (VivaLNK, Campbell, California, USA) for an intensive 3-day training bootcamp. In addition to physiological parameters, CST demographics, event diaries and Maslach Burnout Inventory scores were recorded prospectively during exposure to three scenarios: interactive lectures, clinical skills simulation and non-technical (communication) training. Results: Baseline heart rate (BHR, 60 bpm (range 39-81 bpm)) and baseline respiratory rate (14/min (11-18/min)) varied considerably and did not correlate (rho 0.076, p=0.772). BHR was associated with weekly exercise performed (66 bpm (<1 hour) vs 43 bpm (>5 hour), rho -0.663, p=0.004). Trainee response (standardised median heart rate vs BHR) revealed heart rate was related proportionately to lectures (71 bpm, p<0.001), non-technical skills training (79 bpm, p<0.001) and clinical skills simulation (88 bpm, p<0.001). Respiratory rate responded similarly (p<0.001 in each case). Heart rate during clinical skills simulation was associated with emotional exhaustion (rho 0.493, p=0.044), but maximum heart rate was unrelated to CSTs' perceived peak stressors. Discussion: Stress response, as derived from positive sympathetic heart rate drive varied over two-fold, with a direct implication on oxygen uptake and energy expenditure, and highlighting the daily physical demands placed upon clinicians.

Cardiopulmonary fitness predicts postoperative major morbidity after esophagectomy for patients with cancer.

Surgery for radical treatment of esophageal cancer (EC) carries significant inherent risk. The objective identification of patients who are at high risk of complications is of importance. In this study the prognostic value of cardiopulmonary fitness variables (CPF) derived from cardiopulmonary exercise testing (CPET) was assessed in patients undergoing potentially curative surgery for EC within an enhanced recovery program. OC patients underwent preoperative CPET using automated breath-by-breath respiratory gas analysis, with measurements taken during a ramped exercise test on a bicycle. The prognostic value of V˙O2Peak , Anaerobic Threshold (AT) and VE/VCO2 derived from CPET were studied in relation to post-operative morbidity, which was collected prospectively, and overall survival. Consecutive 120 patients were included for analysis (median age 65 years, 100 male, 75 neoadjuvant therapy). Median AT in the cohort developing major morbidity (Clavien-Dindo classification >2) was 10.4 mL/kg/min compared with 11.3 mL/kg/min with no major morbidity (P = 0.048). Median V˙O2Peak in the cohort developing major morbidity was 17.0 mL/kg/min compared with 18.7 mL/kg/min in the cohort (P = 0.009). V˙O2Peak optimum cut-off was 17.0 mL/kg/min (sensitivity 70%, specificity 53%) and for AT was 10.5 mL/kg/min (sensitivity 60%, specificity 44%). Multivariable analysis revealed V˙O2Peak to be the only independent factor to predict major morbidity (OR 0.85, 95% CI 0.75-0.97, P = 0.018). Cumulative survival was associated with operative morbidity severity (χ2  = 4.892, df = 1, P = 0.027). These results indicate that V˙O2Peak as derived from CPET is a significant predictor of major morbidity after oesophagectomy highlighting the physiological importance of cardiopulmonary fitness.

Src family kinases, HCK and FGR, associate with local inflammation and tumour progression in colorectal cancer.

BACKGROUND: In colorectal cancer (CRC), inflammatory responses have been reported to associate with patient survival. However, the specific signalling pathways responsible for regulating inflammatory responses are not clear. Src family kinases (SFKs) impact tumourigenic processes, including inflammation. METHODS: The relationship between SFK expression, inflammatory responses and cancer specific survival (CSS) in stage I-III CRC patients was assessed using immunohistochemistry on a 272 patient discovery cohort and an extended 822 patient validation cohort. RESULTS: In the discovery cohort, cytoplasmic FGR associated with improved CSS (P = 0.019), with membrane HCK (p = 0.093) trending towards poorer CSS. In the validation cohort membrane FGR (p = 0.016), membrane HCK (p = 0.019), and cytoplasmic HCK (p = 0.030) all associated with poorer CSS. Both markers also associated with decreased proliferation and cytotoxic T-lymphocytes (all p < 0.05). Furthermore, cytoplasmic HCK was an independent prognostic marker compared to common clinical factors. To assess synergy a combine FGR + HCK score was assessed. The membrane FGR + HCK score strengthened associations with poor prognosis (p = 0.006), decreased proliferation (p < 0.001) and cytotoxic T-lymphocytes (p < 0.001). CONCLUSIONS: SFKs associate with prognosis and the local inflammatory response in patients with stage I-III CRC. Active membrane FGR and HCK work in parallel to promote tumour progression and down-regulation of the local inflammatory lymphocytic response.

Systematic Review and Meta-Analysis of the Prognostic Significance of Neutrophil-Lymphocyte Ratio (NLR) After R0 Gastrectomy for Cancer.

PURPOSE: A meta-analysis was performed to evaluate the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients undergoing potentially curative gastrectomy for cancer (GC). METHODS: Thomson Reuters Web of Science, Ovid MEDLINE(R) and PUBMED databases were searched for relevant articles using search terms neutrophil-lymphocyte ratio (NLR), GC and survival. Articles reporting overall survival (OS), cancer-specific survival and disease-free survival (DFS), in patients undergoing R0 gastrectomy, were studied. RESULTS: Articles numbering 365 were identified during the preliminary search, and 10 containing 4164 patients were included in the final review. Most patients were > 60 years of age, male (67%) and 2239 (53.8%) had pT3 disease. The number of NLR dichotomization thresholds reported numbered 7, with 2.00 and 3.00 (n = 2) the most common. NLR was associated with poor survival in eight studies with hazard ratios ranging from 1.54 (95% confidence interval (CI) 1.26-1.89) to 2.99 (1.99-4.49). Pooled odds ratio (OR) for OS was 2.31 (1.40-3.83, p = 0.001) and for DFS 2.72 (1.14-6.54, p = 0.020). Four studies presented T-stage data, OR 1.62 (1.33-1.96, p < 0.001). CONCLUSION: NLR is an important prognostic indicator associated with both OS and DFS after R0 resection of GC, but the critical level is equivocal.