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.

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.

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.

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.

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.

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.

Surgical Education's 100 Most Cited Articles: A Bibliometric Analysis.

BACKGROUND: Bibliometric analysis highlights the key topics and publications, which have shaped surgical education. Here, the 100 most cited articles in the arena of surgical education were analyzed. METHODS: Thomson Reuters Web of Science was interrogated using the keyword search terms "surgery" and ("learning" or "skills" or "competence" or "assessment" or "training" or "procedure-based assessments" or "performance" or "technical skills" or "curriculum" or "education" or "mentoring"] to identify all English language full articles, and the 100 most cited articles were analyzed by topic, journal, author, year, institution, and country of origin. RESULTS: A total of 403,733 eligible articles were returned and the median citation number was 164 (range: 107-1018). The most cited article (by Seymour, Yale University School of Medicine, Annals of Surgery, 1018 citations) focused on the use of virtual reality surgical simulation training. Annals of Surgery published the highest number of articles and received the most citations (n = 16, 3715 citations). The countries with the greatest number of publications were the USA (n = 45), Canada (n = 19), and the UK (n = 18). The commonest topics included simulation (n = 45) and assessment of clinical competence (n = 40). CONCLUSION: Surgical skill acquisition and assessment was the area of focus of 85% of the most cited contemporary articles, and this study provides the most cited references, serving as a guide as to what makes a citable published work in the field of surgical education.

Relationship between tumour PTEN/Akt/COX-2 expression, inflammatory response and survival in patients with colorectal cancer.

In patients with colorectal cancer (CRC), local and systemic inflammatory responses have been extensively reported to associate with cancer survival. However, the specific signalling pathways responsible for inflammatory responses are not clear. The PTEN/Akt pathway is a plausible candidate as it may play a role in mediating inflammation via COX-2, and has been associated with cancer progression. This study therefore examined the relationship between tumour PTEN/Akt/COX-2 expression, inflammatory responses and survival in CRC patients using a tissue microarray.In 201 CRC patients, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (12.0yrs v 7.3yrs, P=0.032), poorer differentiation (P=0.032), venous invasion (P=0.008) and peritoneal involvement (P=0.004). Patients were stratified for peri-nuclear expression of COX-2 to examine associations with inflammatory responses. In patients with absent peri-nuclear COX-2 expression, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (11.9yrs v 5.4yrs, P=0.001), poorer differentiation (P=0.018), venous invasion (P=0.003) and peritoneal involvement (P=0.001). However, no associations were seen with either the local or systemic inflammatory responses.In CRC patients, tumour-specific PTEN/Akt pathway activation was significantly associated with poorer CSS, particularly when peri-nuclear COX-2 expression was absent. However, activation of the PTEN/Akt pathway appears not to be responsible for the regulation of inflammatory responses.

The relationship between genetic profiling, clinicopathological factors and survival in patients undergoing surgery for node-negative colorectal cancer: 10-year follow-up.

PURPOSE: The introduction of the bowel cancer screening programme has resulted in increasing numbers of patients being diagnosed with node-negative disease. Unfortunately, approximately 30 % will develop recurrence following surgery. Given the toxicity associated with adjuvant chemotherapy, it is important to identify high-risk patients who may benefit from adjuvant therapy. This study aims to identify which clinicopathological factors and genetic profiling markers predict outcome in node-negative disease. METHODS: Forty-nine microsatellite stable (MSS) patients undergoing curative resection between 1991 and 1993 were included. Local immune response was assessed by Klintrup criteria and vascular invasion status assessed through Miller's elastin staining. Comparative genomic hybridisation (CGH) on a range of loci provided data on allelic imbalance. Analysis of survival included clinicopathological and CGH data in a multivariate (Cox) model. RESULTS: On binary logistical regression analysis, 4p deletion was independently associated with low Klintrup score (HR 0.16; 95 % CI (0.03-0.96); P = 0.045), venous invasion (HR 4.19; 95 % CI (1.08-16.29); P = 0.039) and higher Dukes' stage (HR 6.43; 95 % CI (1.22-33.97); P = 0.028). Minimum follow-up was 109 months and there were 24 cancer deaths. On multivariate analysis, high Klintrup score (HR 0.33; 95 % CI (0.12-0.93); P = 0.036), 4p- (HR 4.01; 95 % CI (1.58-10.21); P = 0.004) and 5q- (HR 3.81; 95 % CI (1.54-9.47); P = 0.004) were significantly associated with survival. CONCLUSION: 4p-, 5q- and low Klintrup score were independently associated with poor cancer-specific survival in node-negative MSS colorectal cancer. Confirmatory work in a larger cohort is needed to determine whether these markers may be used to identify patients who may benefit from adjuvant chemotherapy.

The bodies fight against cancer: is human leucocyte antigen (HLA) class 1 the key?

INTRODUCTION: Loss of human leucocyte antigen (HLA) class I expression has been implicated in tumour progression and metastasis; however, studies reporting its relationship with long-term survival are few in number with conflicting reports. The aim of this review was to assess the prognostic value of HLA class I expression in gastrointestinal cancer. METHODS: Major electronic databases, including Medline, Embase, Cochrane Library and Pubmed were searched for original studies. Two independent reviewers assessed each study against inclusion and exclusion criteria. All data were specific to gastrointestinal cancer surgery. RESULTS: Fourteen original studies were included in this present review. In oesophageal cancer, reduced expression of HLA-A, HLA-B, HLA-C and HLA-G were associated with poorer survival. However, in gastric and colorectal cancer, the prognostic value of HLA-A, HLA-B, HLA-C and HLA-G remains conflicting. Antibody use and reporting methodology was different between all 14 studies examined. CONCLUSION: Variability in antibody use makes it difficult to validate HLA class I expression as an independent prognostic marker in GI cancer. Consensus guidelines, incorporating heavy and light chain antibodies, are required with further studies on HLA class I expression being performed to validate its prognostic value.