Publications
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Knight WRC, McEwen R, Byrne BE, et al., 2020, Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus, European Journal of Surgical Oncology, ISSN: 0748-7983
BackgroundPrognostication in oesophageal cancer on the basis of preoperative variables is challenging. Many of the accepted predictors of survival are only derived after surgical treatment and may be influenced by neoadjuvant therapy. This study aims to explore the relationship between pre-treatment endoscopic tumour morphology and postoperative survival.MethodsPatients with endoscopic descriptions of tumours were identified from the prospectively managed databases including the OCCAMS database. Tumours were classified as exophytic, ulcerating or stenosing. Kaplan Meier survival analysis and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals.Results262 patients with oesophageal adenocarcinoma undergoing potentially curative resection were pooled from St Thomas’ Hospital (161) and the OCCAMS database (101). There were 70 ulcerating, 114 exophytic and 78 stenosing oesophageal adenocarcinomas. Initial tumour staging was similar across all groups (T3/4 tumours 71.4%, 70.2%, 74.4%). Median survival was 55 months, 51 months and 36 months respectively (p < 0.001). Rates of lymphovascular invasion (P = 0.0176), pathological nodal status (P = 0.0195) and pathological T stage (P = 0.0007) increased from ulcerating to exophytic to stenosing lesions. Resection margin positivity was 21.4% in ulcerating tumours compared to 54% in stenosing tumours (p < 0.001). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on multivariable analysis (HR 0.56 95% CI 0.31–0.93, HR 0.42 95% CI 0.21–0.82).ConclusionThis study demonstrates that endoscopic morphology may be an important pre-treatment prognostic factor in oesophageal cancer. Ulcerating, exophytic and stenosing tumours may represent different pathological processes and tumour biology.
Markar SR, Ni M, Gisbertz SS, et al., 2020, Implementation of Minimally Invasive Esophagectomy From a Randomized Controlled Trial Setting to National Practice, JOURNAL OF CLINICAL ONCOLOGY, Vol: 38, Pages: 2130-+, ISSN: 0732-183X
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- Citations: 46
Curtis NJ, Foster JD, Miskovic D, et al., 2020, Association of Surgical Skill Assessment With Clinical Outcomes in Cancer Surgery, JAMA SURGERY, Vol: 155, Pages: 590-598, ISSN: 2168-6254
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- Citations: 68
Rahman SA, Walker RC, Lloyd MA, et al., 2020, Machine learning to predict early recurrence after oesophageal cancer surgery, BRITISH JOURNAL OF SURGERY, Vol: 107, Pages: 1042-1052, ISSN: 0007-1323
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- Citations: 27
Muthuswamy K, Fisher R, Mavroveli S, et al., 2020, Assessment of technical skills in axillary lymph node dissection, Annals of Surgery, ISSN: 0003-4932
Objective A simulator to enable safe practice and assessment of ALND has been designed, and face, content and construct validity has been investigated.Summary and Background Data The reduction in the number of ALNDs conducted has led to decreased resident exposure and confidence. MethodsA cross-sectional multi-center observational study was carried out between July 2017 to August 2018. Following model development, 30 surgeons ofvarying experience (n=9 ‘experts’, n=11 ‘senior residents’ and n=10 ‘junior residents’) were asked to perform a simulated ALND. Face and content validity questionnaires were administered immediately after ALND. All ALND procedures were retrospectively assessed by two attending breast surgeons, blinded to operator identity, using a video-based assessment tool and an end product assessment tool.ResultsStatistically significant differences between groups were observed across all operative sub-phases on theaxillary clearance assessment tool (p<0.001). Significant differences between groups were observed for overall procedure quality (p<0.05) and total number of lymph nodes harvested (p<0.001). However, operator grade could not be distinguished across other end product variables such as axillary vein damage (p=0.864) and long thoracic nerve injury R1 ALND Structured abstract(p=0.094). Overall, participants indicated that the simulator has good anatomical (median score >7) and procedural realism (median score >7).ConclusionsVideo based analysis demonstrates construct validity for ALND assessment. Given reduced ALND exposure, this simulation is a useful adjunct for both technical skills training and formative Deanery orFaculty administered assessments.
Leff DR, Muthuswamy K, Fisher R, et al., 2020, Assessment of Technical Skills in Axillary Lymph Node Dissection, Annals of Surgery, ISSN: 0003-4932
Markar SR, Griffiths EA, Behrens P, et al., 2020, Protocol for LAsting Symptoms after Oesophageal Resectional Surgery (LASORS): multicentre validation cohort study, BMJ OPEN, Vol: 10, ISSN: 2044-6055
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- Citations: 2
de Vries FEE, Hodgkinson JD, Claessen JJM, et al., 2020, Long-term outcomes after contaminated complex abdominal wall reconstruction, HERNIA, Vol: 24, Pages: 459-468, ISSN: 1265-4906
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- Citations: 18
Hodgkinson JD, de Vries FEE, Claessen JJM, et al., 2020, The development and validation of risk-stratification models for short-term outcomes following contaminated complex abdominal wall reconstruction, HERNIA, Vol: 24, Pages: 449-458, ISSN: 1265-4906
Markar SR, Ni M, Mackenzie H, et al., 2020, The effect of time between procedures upon the proficiency gain period for minimally invasive esophagectomy, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 34, Pages: 2703-2708, ISSN: 0930-2794
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- Citations: 2
Vadhwana B, Belluomo I, Boshier PR, et al., 2020, Impact of oral cleansing strategies on exhaled volatile organic compound levels, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Vol: 34, ISSN: 0951-4198
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- Citations: 10
Jammula S, Katz-Summercorn AC, Li X, et al., 2020, Identi fication of Subtypes of Barrett ?s Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Pro files and Integration of Transcriptome and Genome Data, GASTROENTEROLOGY, Vol: 158, Pages: 1682-+, ISSN: 0016-5085
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- Citations: 42
Halliday LJ, Doran SLF, Sgromo B, et al., 2020, Variation in esophageal anastomosis technique-the role of collaborative learning, DISEASES OF THE ESOPHAGUS, Vol: 33, ISSN: 1120-8694
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- Citations: 6
Tukanova K, Markar SR, Jamel S, et al., 2020, An international comparison of the utilisation of and outcomes from minimal access surgery for the treatment of common abdominal surgical emergencies, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 34, Pages: 2012-2018, ISSN: 0930-2794
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- Citations: 2
Abbassi-Ghadi N, Antonowicz S, McKenzie J, et al., 2020, De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma, Cancer Research, Vol: 80, Pages: 2764-2774, ISSN: 0008-5472
The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging can support objective diagnosis in minutes using a routine frozen tissue section. However, whether mass spectrometry imaging can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here we used desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariable models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (area-under-curve = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in pre-malignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened GPL chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of pre-malignant tissues and unveils mechanisms of phospholipidomic reprogramming. These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.
Markar SR, Arhi C, Wiggins T, et al., 2020, Reintervention after antireflux surgery for gastroesophageal reflux disease in England, Annals of Surgery, Vol: 271, Pages: 709-715, ISSN: 0003-4932
BACKGROUND: After antireflux surgery, highly variable rates of recurrent gastroesophageal reflux disease (GERD) have been reported. OBJECTIVE: To identify the occurrence and risk factors of recurrent GERD requiring surgical reintervention or medication. METHODS: The Hospital Episode Statistics database was used to identify adults in England receiving primary antireflux surgery for GERD in 2000 to 2012 with follow-up through 2014, and the outcome was surgical reintervention. In a subset of participants, the Clinical Practice Research Datalink was additionally used to assess proton pump inhibitor therapy for at least 6 months (medical reintervention). Risk factors were assessed using multivariable Cox regression providing adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: Among 22,377 patients who underwent primary antireflux surgery in the Hospital Episode Statistics dataset, 811 (3.6%) had surgical reintervention, with risk factors being age 41 to 60 years (HR = 1.22, 95% CI 1.03-1.44), female sex (HR = 1.5; 95% CI 1.3-1.74), white ethnicity (HR = 1.71, 95% CI 1.06-2.77), and low hospital annual volume of antireflux surgery (HR = 1.32, 95% CI 1.04-1.67). Among 2005 patients who underwent primary antireflux surgery in the Clinical Practice Research Datalink dataset, 189 (9.4%) had surgical reintervention and 1192 (59.5%) used proton pump inhibitor therapy, with risk factors for the combined outcome being age >60 years (HR = 2.38, 95% CI 1.81-3.13) and preoperative psychiatric morbidity (HR = 1.58, 95% CI 1.25-1.99). CONCLUSION: At least 3.6% of patients may require surgical reintervention and 59.5% medical therapy following antireflux surgery in England. The influence of patient characteristics and hospital volume highlights the need for patient selection and surgical experience in successful antireflux surgery.
Harris A, Butterworth J, Boshier PR, et al., 2020, Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials., Ann Surg
OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098. TRIAL REGISTRATION NUMBER: ISRCTN59036820, ISRCTN10386621.
Ni M, Borsci S, Walne S, et al., 2020, The Lean and Agile Multi-dimensional Process (LAMP) - a new framework for rapid and iterative evidence generation to support health-care technology design and development, Expert Review of Medical Devices, Vol: 17, Pages: 277-288, ISSN: 1743-4440
Introduction: Health technology assessments (HTA) are tools for policymaking and resource allocation. Early HTAs are increasingly used in design and development of new technologies. Conducting early HTAs is challenging, due to a lack of evidence and significant uncertainties in the technology and the market. A multi-disciplinary approach is considered essential. However, an operational framework that can enable the integration of multi-dimensional evidence into commercialization remains lacking.Areas covered: We developed the Lean and Agile Multi-dimensional Process (LAMP), an early HTA framework, for embedding commercial decision-making in structured evidence generation activities, divided into phases. Diverse evidence in unmet needs, user acceptance, cost-effectiveness, and market competitiveness are being generated in increasing depth. This supports the emergence of design and value propositions that align technology capabilities and clinical and user needs.Expert opinion: We have been applying LAMP to working with medical device and diagnostic industry in the UK. The framework can be adapted to suit different technologies, decision needs, time scales, and resources. LAMP offers a practical solution to the multi-disciplinary approach. Methodologists drive the process by performing evidence generation and synthesis as and by enabling interactions between manufacturers, designers, clinicians, and other key stakeholders.
Tukanova K, Papi E, Jamel S, et al., 2020, Assessment of chest wall movement following thoracotomy: a systematic review, JOURNAL OF THORACIC DISEASE, Vol: 12, Pages: 1031-+, ISSN: 2072-1439
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- Citations: 10
Goh YM, Antonowicz S, Boshier P, et al., 2020, Metabolic biomarkers of squamous cell carcinoma of the aerodigestive tract: a systematic review and quality assessment, Oxidative Medicine and Cellular Longevity, Vol: 2020, Pages: 1-13, ISSN: 1942-0900
Introduction. Aerodigestive squamous cell carcinomas (ASCC) constitute a major source of global cancer deaths. Patients typically present with advanced, incurable disease, so new means of detecting early disease are a research priority. Metabolite quantitation is amenable to point-of-care analysis and can be performed in ASCC surrogates such as breath and saliva. The purpose of this systematic review is to summarise progress of ASCC metabolomic studies, with an emphasis on the critical appraisal of methodological quality and reporting. Method. A systematic online literature search was performed to identify studies reporting metabolic biomarkers of ASCC. This review was conducted in accordance with the recommendations of the Cochrane Library and MOOSE guidelines. Results. Thirty studies comprising 2117 patients were included in the review. All publications represented phase-I biomarker discovery studies, and none validated their findings in an independent cohort. There was heterogeneity in study design and methodological and reporting quality. Sensitivities and specificities were higher in oesophageal and head and neck squamous cell carcinomas compared to those in lung squamous cell carcinoma. The metabolic phenotypes of these cancers were similar, as was the kinetics of metabolite groups when comparing blood, tissue, and breath/saliva concentrations. Deregulation of amino acid metabolism was the most frequently reported theme. Conclusion. Metabolite analysis has shown promising diagnostic performance, especially for oesophageal and head and neck ASCC subtypes, which are phenotypically similar. However, shortcomings in study design have led to inconsistencies between studies. To support future studies and ultimately clinical adoption, these limitations are discussed.
Campbell PJ, Getz G, Korbel JO, et al., 2020, Pan-cancer analysis of whole genomes, Nature, Vol: 578, Pages: 82-93, ISSN: 0028-0836
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
Bornschein J, Wernisch L, Secrier M, et al., 2019, Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction, International Journal of Cancer, Vol: 145, Pages: 3389-3401, ISSN: 0020-7136
Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment‐naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina‐HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune‐response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed.
Tsai AY-C, Mavroveli S, Miskovic D, et al., 2019, Surgical quality assurance in COLOR III standardization and competency assessment in a randomized controlled trial, Annals of Surgery, Vol: 270, Pages: 768-774, ISSN: 0003-4932
Objective: The aim of this study was to develop an objective and reliable surgical quality assurance system (SQA) for COLOR III, an international multicenter randomized controlled trial (RCT) comparing transanal total mesorectal excision (TaTME) with laparoscopic approach for rectal cancer.Background of Summary Data: SQA influences outcome measures in RCTs such as lymph nodes harvest, in-hospital mortality, and locoregional cancer recurrence. However, levels of SQA are variable.Method: Hierarchical task analysis of TaTME was performed. A 4-round Delphi methodology was applied for standardization of TaTME steps. Semistructured interviews were conducted in round 1 to identify key steps and tasks, which were rated as mandatory, optional, or prohibited in rounds 2 to 4 using questionnaires. Competency assessment tool (CAT) was developed and its content validity was examined by expert surgeons. Twenty unedited videos were assessed to test reliability using generalizability theory.Results: Eighty-three of 101 surgical tasks identified reached 70% agreement (26 mandatory, 56 optional, and 1 prohibited). An operative guide of standardized TaTME was created. CAT is matrix of 9 steps and 4 performance qualities: exposure, execution, adverse event, and end-product. The overall G-coefficient was 0.883. Inter-rater and interitem reliability were 0.883 and 0.986. To enter COLOR III, 2 unedited TaTME and 1 laparoscopic TME videos were submitted and assessed by 2 independent assessors using CAT.Conclusion: We described an iterative approach to develop an objective SQA within multicenter RCT. This approach provided standardization, the development of reliable and valid CAT, and the criteria for trial entry and monitoring surgical performance during the trial.
Markar S, Lagergren P, Zaninotto G, et al., 2019, AUGIS abstracts 2019, 22nd Annual Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland (AUGIS), Publisher: WILEY, Pages: 5-5, ISSN: 0007-1323
Turkington RC, Knight LA, Blayney JK, et al., 2019, Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma, GUT, Vol: 68, Pages: 1918-1927, ISSN: 0017-5749
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- Citations: 16
Boshier PR, Swaray A, O'Sullivan A, et al., 2019, Predictive models of survival after resection of oesophageal adenocarcinoma: a systematic review and multicentre validation of models, 22nd Annual Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland (AUGIS), Publisher: WILEY, Pages: 66-66, ISSN: 0007-1323
Markar SR, Vidal-Diez A, Patel K, et al., 2019, Comparison of Surgical Intervention and Mortality for Seven Surgical Emergencies in England and the United States, ANNALS OF SURGERY, Vol: 270, Pages: 806-812, ISSN: 0003-4932
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- Citations: 8
Hodgkinson JD, Oke SM, Warusavitarne J, et al., 2019, Incisional hernia and enterocutaneous fistula in patients with chronic intestinal failure: prevalence and risk factors in a cohort of patients referred to a tertiary centre, COLORECTAL DISEASE, Vol: 21, Pages: 1288-1295, ISSN: 1462-8910
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- Citations: 1
Curtis NJ, Conti JA, Dalton R, et al., 2019, 2D versus 3D laparoscopic total mesorectal excision: a developmental multicentre randomised controlled trial, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 33, Pages: 3370-3383, ISSN: 0930-2794
AimsThe role of laparoscopy in rectal cancer has been questioned. 3D laparoscopic systems are suggested to aid optimal surgical performance but have not been evaluated in advanced procedures. We hypothesised that stereoscopic imaging could improve the performance of laparoscopic total mesorectal excision (TME).MethodsA multicentre developmental randomised controlled trial comparing 2D and 3D laparoscopic TME was performed (ISRCTN59485808). Trial surgeons were colorectal consultants that had completed their TME proficiency curve and underwent stereoscopic visual testing. Patients requiring elective laparoscopic TME with curative intent were centrally randomised (1:1) to 2D or 3D using Karl Storz IMAGE1 S D3-Link™ and 10-mm TIPCAM®1S 3D passive polarising laparoscopic systems. Outcomes were enacted adverse events as assessed by the observational clinical human reliability analysis technique, intraoperative data, 30-day patient outcomes, histopathological specimen assessment and surgeon cognitive load.Results88 patients were included. There were no differences in patient or tumour demographics, surgeon stereopsis, case difficulty, cognitive load, operative time, blood loss or conversion between the trial arms. 1377 intraoperative adverse events were identified (median 18 per case, IQR 14–21, range 2–49) with no differences seen between the 2D and 3D arms (18 (95% CI 17–21) vs. 17 (95% CI 16–19), p = 0.437). 3D laparoscopy had non-significantly higher mesorectal fascial plane resections (94 vs. 77%, p = 0.059; OR 0.23 (95% CI 0.05–1.16)) but equal lymph node yield and circumferential margin distance and involvement. 30-day morbidity, anastomotic leak, re-operation, length of stay and readmission rates were equal between the 2D and 3D arms.ConclusionFeasibility of performing multicentre 3D laparoscopic multicentre trials of specialist performed complex procedures is shown. 3D imaging did not alter the nu
Arhi CS, Markar S, Burns EM, et al., 2019, Delays in referral from primary care are associated with a worse survival in patients with esophagogastric cancer, Diseases of the Esophagus, Vol: 32, Pages: 1-11, ISSN: 1120-8694
NICE referral guidelines for suspected cancer were introduced to improve prognosis by reducing referral delays. However, over 20% of patients with esophagogastric cancer experience three or more consultations before referral. In this retrospective cohort study, we hypothesize that such a delay is associated with a worse survival compared with patients referred earlier. By utilizing Clinical Practice Research Datalink, a national primary care linked database, the first presentation, referral date, a number of consultations before referral and stage for esophagogastric cancer patients were determined. The risk of a referral after one or two consultations compared with three or more consultations was calculated for age and the presence of symptom fulfilling the NICE criteria. The risk of death according to the number of consultations before referral was determined, while accounting for stage and surgical management. 1307 patients were included. Patients referred after one (HR 0.80 95% CI 0.68-0.93 p = 0.005) or two consultations (HR 0.81 95% CI 0.67-0.98 p = 0.034) demonstrated significantly improved prognosis compared with those referred later. The risk of death was also lower for patients who underwent a resection, were younger or had an earlier stage at diagnosis. Those presenting with a symptom fulfilling the NICE criteria (OR 0.27 95% CI 0.21-0.35 p < 0.0001) were more likely to be referred earlier. This is the first study to demonstrate an association between a delay in referral and worse prognosis in esophagogastric patients. These findings should prompt further research to reduce primary care delays.
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