Additional value of EUS in oesophageal cancer patients staged N0 on PET/CT: validation of a prognostic model

Background Lymph node metastases are a major prognostic indicator in oesophageal cancer. Radiological staging largely influences treatment decisions and is becoming more reliant on PET and CT. However, the sensitivity of these modalities is suboptimal and is known to under-stage disease. The primary aim of this study was to validate a published prognostic model in oesophageal cancer patients staged N0 with PET/CT, which showed that EUS nodal status was an independent predictor of survival. The secondary aim was to assess the prognostic significance of pathological lymph node metastases in this cohort. Methods An independent validation cohort included 139 consecutive patients from a regional upper gastrointestinal cancer network staged N0 with PET/CT between 1st January 2013 and 31st June 2015. Replicating the original study, two Cox regression models were produced: one included EUS T-stage and EUS N-stage, and one included EUS T-stage and EUS N0 versus N+. The primary outcome of the prognostic model was overall survival (OS). Kaplan–Meier analysis assessed differences in OS between pathological node-negative (pN0) and node-positive (pN+) groups. A p value of < 0.05 was considered statistically significant. Results The mean OS of the validation cohort was 29.8 months (95% CI 27.1–35.2). EUS T-stage was significantly and independently associated with OS in both models (p = 0.011 and p = 0.012, respectively). EUS N-stage and EUS N0 versus N+ were not significantly associated with OS (p = 0.553 and p = 0.359, respectively). There was a significant difference in OS between pN0 and pN+ groups (χ2 13.315, df 1, p < 0.001). Conclusion Lymph node metastases have a significant detrimental effect on OS. This validation study did not replicate the results of the developed prognostic model but the continued benefit of EUS in patients staged N0 with PET/CT was demonstrated. EUS remains a valuable component of a multi-modality approach to oesophageal cancer staging

Systematic review and meta-analysis of the prognostic significance of Neutrophil-Lymphocyte Ratio (NLR) After R0 gastrectomy for cancer

Abstract 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 &gt; 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 &lt; 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. </jats:sec

Prognostic significance of serum inflammatory markers in gastric cancer

Background The aim of this study was to assess the relative prognostic value of biomarkers to measure the systemic inflammatory response (SIR) and improve prognostic modeling in a cohort of patients undergoing potentially curative surgery for gastric adenocarcinoma. The hypothesis was that a single SIR biomarker would be associated with the most prognostic value. Methods Consecutive 331 patients undergoing surgery for gastric cancer between 2004 and 2016 within a regional UK cancer network were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow Prognostic Score, and differential white cell counts were obtained before surgery, and correlated with histopathological factors (pTNM stage, differentiation, and vascular invasion) and survival. Primary outcome measures were disease-free (DFS) and overall survival (OS). Results Consecutive 331 patients were identified and 291 underwent potentially curative gastrectomy for adenocarcinoma. On univariable DFS analysis, female gender (p = 0.027), proximal location (p = 0.018), pT stage (p < 0.001), pN stage (p < 0.001), pTNM stage (p < 0.001), vascular invasion (p < 0.001), poor differentiation (p = 0.001), lymph node ratio (p < 0.001), R1 status (p < 0.001), platelet count (p = 0.038), and mGPS (p = 0.001) were significantly associated with poor survival. The mGPS was associated with advanced pT stage (p = 0.001), pTNM stage (p = 0.013), and poor differentiation (p = 0.030). On multivariable DFS analysis, mGPS [hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.35–4.65, p = 0.011] was the only inflammatory marker to retain independent significance. Multivariable OS analysis revealed similar findings; mGPS (HR 2.75, (95% CI 1.65– 4.59), p < 0.001). Conclusion mGPS is an important and only SIR-related prognostic biomarker independently associated with both DFS and OS in gastric cance

Team strategic philosophy: requiem for the infinite game

Deliberate accountability has arrived in the medical arena, producing an age of reward for measured performance, and belief in publicizing metrics to ensure clarity, with winning defined as hitting targets, whereby staff are incentivised by arbitrary objectives. Finite game theory declares that players are known, rules are fixed, and the objective agreed, but infinite game theory asserts that players are both known and unknown, rules are changeable, and the objective is to perpetuate the game; these standards are clearly at odds and risk real world chaos in global universal medical education and clinical outcomes and functioning. Five principles are necessary to lead an infinite game: first, a fair basis, such that sacrifices for its advancement are promoted; second, a trusting blame-free team culture and environment; third, competitors viewed as worthy rivals, rather than adversaries, promoting healthy competition; fourth, existential flexibility when faced with credible evidence; and finally, transformational leadership; including infinite game theory into healthcare planning may be difficult, but the potential rewards are surely worth the existential fight

Relative Prognostic Value of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Operable Oesophagogastric Cancer

Aims. The aim of this study was to determine the prognostic significance of HER2 receptor expression in operable oesophagogastric adenocarcinoma. Methods. Eighty-five consecutive patients diagnosed with oesophagogastric adenocarcinoma [18 oesophageal (OC), 32 junctional (JC) and 35 gastric (GC)] undergoing potentially curative resection were studied retrospectively. Immunohistochemistry was used to determine HER2 status at endoscopic biopsy and resection specimen. The primary outcome measure was survival. Results. Twenty (24%) patients had HER2 positive tumours which was commoner in JC (14/32, 44% versus 2/18, 11% in OC and 4/35, 11% in GC

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

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

Neutrophil-lymphocyte ratio as a predictor of response to neoadjuvant chemotherapy and survival in oesophageal adenocarcinoma

Background: Inflammation has an important role in cancer survival, yet whether serum markers of inflammation predict response to potentially curative neoadjuvant chemotherapy (NAC) in oesophageal adenocarcinoma (OAC) is controversial. This study aimed to determine whether systemic inflammatory response (SIR) was associated with response to NAC and survival. Methods: Consecutive patients with OAC planned to undergo surgery with curative intent received blood neutrophil and lymphocyte measurements at diagnosis to calculate Neutrophil-lymphocyte ratio (NLR). Pathological variables including pTNM stage, differentiation, vascular invasion, and Mandard Tumour Regression Grade (TRG) were recorded. TRGs 1&2 were taken to represent good response and primary outcome was overall survival (OS). Results: During follow-up of 136 patients, 36 patients (26.5%) suffered recurrence and 69 patients (50.7%) died. Receiver-Operator-Characteristic (ROC) analysis of NLR before NAC predicted poor TRG (area-under-the-curve (AUC) 0.71 (95% confidence interval (CI) 0.58-0.83, p=0.002). On univariable analysis, pT-stage (p<0.001), pN-stage (p<0.001), poor differentiation (p=0.006), margin positivity (p=0.001), poor TRG (p=0.014), and NLR (dichotomised 2.25, p=0.017) were associated with poor OS. but only NLR (Hazard Ratio (HR) 2.28 95% CI (1.03-4.93), p=0.042) retained independent significance on multivariable analysis. Conclusions: Pre-treatment NLR was associated with OAC pathological response to NAC and OS