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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Laparoscopic Surgery's 100 Most Influential Manuscripts: A Bibliometric Analysis.

PURPOSE: Bibliometric analysis of the 100 most cited manuscripts in laparoscopic surgery. MATERIALS AND METHODS: Web of Science database was used to identify all English language full manuscripts with search terms "laparoscop*" and "surg*." The 100 most cited publications were analyzed by; topic, journal, author, year, and institution. RESULTS: In total, 71,524 eligible papers were returned with a median citation of 585.76. The 2 most cited papers received 1635 citations each. Nelson and colleagues, compared laparoscopic with open colectomy for malignancy, and Clavien and colleagues, classified postoperative morbidity by severity. Annals of Surgery published the largest number of papers (n=22), and received most citations (n=12,356). The United States (n=55) and 2004 (n=13) had the highest number of publications. The most ubiquitous topic was cancer treatment (n=35), followed by surgical technique (n=24), and comparison of laparoscopic with open surgery (n=22). CONCLUSIONS: The most cited topic compared laparoscopic surgical techniques and comparisons thereof with open surgery.

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 cancer.

The 100 most cited manuscripts in emergency abdominal surgery: A bibliometric analysis.

BACKGROUND: The number of citations a scientific article receives provides a good indication of its impact within any given field. This bibliometric analysis aimed to identify the 100 most cited articles in Emergency Abdominal Surgery (EAS), to highlight key areas of interest and identify those that have most significantly shaped contemporary clinical practice in this newly evolving surgical specialty. This is of increasing relevance as concerns grow regarding the variable and suboptimal outcomes in Emergency General Surgery. MATERIALS AND METHODS: The Thomson Reuters Web of Science database was used to search using the terms [Emergency AND Abdom* AND Surg*] to identify all English language, full manuscripts. Results were ranked according to citation number. The top 100 articles were further analysed by subject, author, journal, year of publication, institution, and country of origin. RESULTS: The median (range) citation number of the top 100 out of 7433 eligible papers was 131 (1569-97). The most cited paper (by Goldman et al., Massachusetts General Hospital, New England Journal of Medicine; 1569 citations) focused on cardiac risk stratification in non-cardiac surgery. The Journal of Trauma, Injury, Infection and Critical Care published the most papers and received most citations (n = 19; 2954 citations. The majority of papers were published by centres in the USA (n = 52; 9422 citations), followed by the UK (n = 13; 1816 citations). The most common topics of publication concerned abdominal aneurysm management (n = 26) and emergency gastrointestinal surgery (n = 26). CONCLUSION: Vascular surgery, risk assessment and gastrointestinal surgery were the areas of focus for 59% of the contemporary most cited emergency abdominal surgery manuscripts. By providing the most influential references this work serves as a guide to what makes a citable emergency surgery paper.