Imperial College London

DrSherazMarkar

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3312 7657s.markar

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
Year
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334 results found

Challine A, Kirouani M, Markar SR, Tzedakis S, Jaquet R, Piessen G, Dabakoyo-Yonli TS, Lefèvre JH, Lazzati A, Voron Tet al., 2024, MIRO study: Do the results of a randomized controlled trial apply in a real population?, Surgery, Vol: 175, Pages: 1055-1062

BACKGROUND: The aim of our study was to evaluate the external validity of the MIRO randomized controlled trial findings in a similar nationwide setting "real life" population, especially the benefit of a hybrid approach in esophageal resection for pulmonary complication. The external validity of randomized controlled trial findings to the general population with the same condition remains problematic because of the inherent selection bias and rigid inclusion criteria. METHODS: This study was a cohort study from a National Health Database (Programme de Medicalisation des Systemes d'Informations) between 2010 and 2022. All adult patients operated on using Ivor Lewis resection for esophageal cancer were included. We first validated the detection algorithm of postoperative complications in the health database. Then, we assessed the primary outcome, which was the comparison of postoperative severe pulmonary complications, leak rate, and 30-day mortality between the 2 surgical approaches (hybrid versus open) over a decade. RESULTS: Between 2010 and 2012, 162 of 205 patients in the MIRO trial were anonymously identified in the health care database. No difference between randomized controlled trials and healthcare database measurements was found within severe respiratory complications (24% vs 22%, respectively) nor within leak rate (10% vs 9%, respectively). After application of selection criteria according to the MIRO trial, 3,852 patients were included between 2013 and 2022. The hybrid approach was a protective factor against respiratory complications after adjustment for confounding variables (odds ratio = 0.83; 95% confidence interval = 0.71-0.98, P = .025). No significant difference in the 30-day mortality rate or 30-day leakage rate between the types of approach was reported. CONCLUSION: This national cohort study demonstrates the external validity of the MIRO randomized controlled trial findings in a real-life population within France.

Journal article

Down B, Lakunina S, Maynard N, Markar SR, Gordon-Weeks Aet al., 2024, Oncological outcomes of patients with oligometastatic oesophagogastric cancer., Eur J Surg Oncol, Vol: 50

Oligometastatic oesophagogastric cancer was recently defined by consensus as the presence of no more than two metastases and an 18-week period of oncological stability during chemotherapy. The number of patients who fit this criterion and whether their oncological outcome differs from those with multi-metastatic disease is unknown. We analysed a database of 497 patients from 2017 to 2021 with metastatic oesophageal cancer. In total, 36 (7.2%) had oligometastatic disease and significantly improved median overall survival (mOS) versus multi-metastatic disease. In synchronous OMD, mOS was 26.8 months versus 7.3 months and in metachronous OMD, 38.6 months versus 6.1 months (both p < 0.0001). A subset of oligometastatic patients who underwent surgical management of their oligometastases after primary tumour resection demonstrated significantly increased mOS compared with systemic treatment alone (60 months versus 24.4 months; p < 0.038). Oligometastatic oesophagogastric cancer is associated with improved oncological outcome when compared to multi-metastatic disease. Further work is needed to identify patients who will benefit from aggressive treatment of metastatic oesophagogastric cancer.

Journal article

Chidambaram S, Markar SR, 2024, Epidemiology of Esophageal Squamous Cell Carcinoma, Foregut, Vol: 4, Pages: 65-71

Esophageal squamous cell carcinoma (ESCC) is a leading cause of death worldwide, particularly prevalent in Southern and Eastern Africa, and central Asia. Initial studies identified various factors associated with an increased risk of ESCC, leading to subsequent research investigating the underlying biological mechanisms. This narrative review aims to summarize the role of risk factors in ESCC development and propose future research directions. A systematic literature search was conducted using EMBASE, MEDLINE/PubMed, and CENTRAL databases to identify relevant publications. Included studies updated the epidemiology of ESCC, including the incidence, prevalence and mortality and its variations globally. We reported on socio-demographic impact on these geographic variations. We, then, focused on identifying risk factors associated with ESCC. The identified risk factors were categorized into 5 subcategories: smoking, alcohol, dietary factors, environmental factors and infection. Each subcategory’s risk factors were summarized and explored, providing geographical links for these associations. The review emphasizes the current understanding of several risk factors for ESCC, and specifically makes geographical links, and potential explanations for their associations were explored. However, further research is essential to validate these findings and gain insights into their impact on tumor biology.

Journal article

Markar SR, Visser MR, van der Veen A, Luyer MDP, Nieuwenhuijzen G, Stoot JHMB, Tegels JJW, Wijnhoven BPL, Lagarde SM, de Steur WO, Hartgrink HH, Kouwenhoven EA, Wassenaar EB, Draaisma WA, Gisbertz SS, van Berge Henehouwen MI, van der Peet DL, Ruurda JP, van Hillegersberg R, LOGICA Study Group, Dutch Upper Gastrointestinal Cancer Audit Groupet al., 2024, Evolution in Laparoscopic Gastrectomy From a Randomized Controlled Trial Through National Clinical Practice., Ann Surg, Vol: 279, Pages: 394-401

OBJECTIVE: To examine the influence of the LOGICA RCT (randomized controlled trial) upon the practice and outcomes of laparoscopic gastrectomy within the Netherlands. BACKGROUND: Following RCTs the dissemination of complex interventions has been poorly studied. The LOGICA RCT included 10 Dutch centers and compared laparoscopic to open gastrectomy. METHODS: Data were obtained from the Dutch Upper Gastrointestinal Cancer Audit (DUCA) on all gastrectomies performed in the Netherlands (2012-2021), and the LOGICA RCT from 2015 to 2018. Multilevel multivariable logistic regression analyses were performed to assess the effect of laparoscopic versus open gastrectomy upon clinical outcomes before, during, and after the LOGICA RCT. RESULTS: Two hundred eleven patients from the LOGICA RCT (105 open vs 106 laparoscopic) and 4131 patients from the DUCA data set (1884 open vs 2247 laparoscopic) were included. In 2012, laparoscopic gastrectomy was performed in 6% of patients, increasing to 82% in 2021. No significant effect of laparoscopic gastrectomy on postoperative clinical outcomes was observed within the LOGICA RCT. Nationally within DUCA, a shift toward a beneficial effect of laparoscopic gastrectomy upon complications was observed, reaching a significant reduction in overall [adjusted odds ratio (aOR):0.62; 95% CI: 0.46-0.82], severe (aOR: 0.64; 95% CI: 0.46-0.90) and cardiac complications (aOR: 0.51; 95% CI: 0.30-0.89) after the LOGICA trial. CONCLUSIONS: The wider benefits of the LOGICA trial included the safe dissemination of laparoscopic gastrectomy across the Netherlands. The robust surgical quality assurance program in the design of the LOGICA RCT was crucial to facilitate the national dissemination of the technique following the trial and reducing potential patient harm during surgeons learning curve.

Journal article

Cizmic A, Romic I, Balla A, Barabino N, Anania G, Baiocchi GL, Bakula B, Balagué C, Berlth F, Bintintan V, Bracale U, Egberts J-H, Fuchs HF, Gisbertz SS, Gockel I, Grimminger P, van Hillegersberg R, Inaki N, Immanuel A, Korr D, Lingohr P, Mascagni P, Melling N, Milone M, Mintz Y, Morales-Conde S, Moulla Y, Müller-Stich BP, Nakajima K, Nilsson M, Reeh M, Sileri P, Targarona EM, Ushimaru Y, Kim Y-W, Markar S, Nickel F, Mitra ATet al., 2024, An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer., Surg Endosc, Vol: 38, Pages: 488-498

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools design

Journal article

Hall LA, Powell-Brett S, Halle-Smith J, Ward L, Wiggins T, Markar SR, Roberts KJet al., 2024, Pancreatic exocrine insufficiency after non-pancreatic upper gastrointestinal surgery: meta-analysis., Br J Surg, Vol: 111

BACKGROUND: Untreated pancreatic exocrine insufficiency (PEI) results in substantial patient harm. Upper gastrointestinal surgery (bariatric metabolic surgery and oesophagogastric resection) affects the delicate physiology of pancreatic exocrine function and may result in PEI. The aim of this study was to assimilate the literature on incidence, diagnosis, and management of PEI after bariatric metabolic surgery and oesophagogastric resection. METHODS: A systematic review of PubMed, MEDLINE, and Embase databases identified studies investigating PEI after non-pancreatic upper gastrointestinal surgery. Meta-analyses were undertaken for incidence of PEI and benefit of pancreatic enzyme replacement therapy. RESULTS: Among 1620 patients from 24 studies included in quantitative synthesis, 36.0% developed PEI. The incidence of PEI was 23.0 and 50.4% after bariatric metabolic surgery and oesophagogastric resection respectively. Notably, the incidence of PEI was 44% after biliopancreatic diversion with duodenal switch and 66.2% after total gastrectomy. The most common diagnostic test used was faecal elastase 1 (15 of 31 studies), with less than 200 µg/g being diagnostic of PEI. A total of 11 studies considered the management of pancreatic exocrine insufficiency, with 78.6% of patients responding positively to pancreatic enzyme replacement when it was prescribed. CONCLUSION: PEI is common after non-pancreatic upper gastrointestinal surgery and patients may benefit from enzyme replacement therapy.

Journal article

Mortensen HR, Populaire P, Hoffmann L, Moeller DS, Appelt A, Nafteux P, Muijs CT, Grau C, Hawkins MA, Troost EGC, Defraene G, Canters R, Clarke CS, Weber DC, Korevaar EW, Haustermans K, Nordsmark M, Gebski V, Achiam MP, Markar SR, Radhakrishna G, Berbee M, Scartoni D, Orlandi E, Doyen J, Gregoire V, Crehange G, Langendijk J, Lorgelly P, Blommenstein HM, Byskov CS, Ehmsen ML, Jensen MF, Freixas GV, Bütof R, PROTECT consortiumet al., 2024, Proton versus photon therapy for esophageal cancer - A trimodality strategy (PROTECT) NCT050555648: A multicenter international randomized phase III study of neoadjuvant proton versus photon chemoradiotherapy in locally advanced esophageal cancer., Radiother Oncol, Vol: 190

Journal article

Hardvik Åkerström J, Santoni G, von Euler Chelpin M, Chidambaram S, Markar SR, Maret-Ouda J, Ness-Jensen E, Kauppila JH, Holmberg D, Lagergren Jet al., 2023, Decreased Risk of Esophageal Adenocarcinoma After Gastric Bypass Surgery in a Cohort Study From 3 Nordic Countries., Ann Surg, Vol: 278, Pages: 904-909

OBJECTIVE: The objective of this study was to test the hypothesis that bariatric surgery decreases the risk of esophageal and cardia adenocarcinoma. BACKGROUND: Obesity is strongly associated with esophageal adenocarcinoma and moderately with cardia adenocarcinoma, but whether weight loss prevents these tumors is unknown. METHODS: This population-based cohort study included patients with an obesity diagnosis in Sweden, Finland, or Denmark. Participants were divided into a bariatric surgery group and a nonoperated group. The incidence of esophageal and cardia adenocarcinoma (ECA) was first compared with the corresponding background population by calculating standardized incidence ratios (SIR) with 95% CIs. Second, the bariatric surgery group and the nonoperated group were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CI, adjusted for sex, age, comorbidity, calendar year, and country. RESULTS: Among 748,932 participants with an obesity diagnosis, 91,731 underwent bariatric surgery, predominantly gastric bypass (n=70,176; 76.5%). The SIRs of ECA decreased over time after gastric bypass, from SIR=2.2 (95% CI, 0.9-4.3) after 2 to 5 years to SIR=0.6 (95% CI, <0.1-3.6) after 10 to 40 years. Gastric bypass patients were also at a decreased risk of ECA compared with nonoperated patients with obesity [adjusted HR=0.6, 95% CI, 0.4-1.0 (0.98)], with decreasing point estimates over time. Gastric bypass was followed by a strongly decreased adjusted risk of esophageal adenocarcinoma (HR=0.3, 95% CI, 0.1-0.8) but not of cardia adenocarcinoma (HR=0.9, 95% CI, 0.5-1.6), when analyzed separately. There were no consistent associations between other bariatric procedures (mainly gastroplasty, gastric banding, sleeve gastrectomy, and biliopancreatic diversion) and ECA. CONCLUSIONS: Gastric bypass surgery may counteract the development of esophageal adenocarcinoma in morbidly obese individuals.

Journal article

Owen RP, Chidambaram S, Griffiths EA, Sultan J, Phillips AW, Vohra R, Preston S, Gossage J, Hanna GB, Underwood TJ, Maynard N, Markar SR, MUSOIC study groupet al., 2023, Multicenter, Prospective Cohort Study of Oesophageal Injuries and Related Clinical Outcomes (MUSOIC study)., Ann Surg, Vol: 278, Pages: 910-917

OBJECTIVE: To identify prognostic factors associated with 90-day mortality in patients with oesophageal perforation (OP), and characterize the specific timeline from presentation to intervention, and its relation to mortality. BACKGROUND: OP is a rare gastro-intestinal surgical emergency with a high mortality rate. However, there is no updated evidence on its outcomes in the context of centralized esophago-gastric services; updated consensus guidelines; and novel non-surgical treatment strategies. METHODS: A multi-center, prospective cohort study involving eight high-volume esophago-gastric centers (January 2016 to December 2020) was undertaken. The primary outcome measure was 90-day mortality. Secondary measures included length of hospital and ICU stay, and complications requiring re-intervention or re-admission. Mortality model training was performed using random forest, support-vector machines, and logistic regression with and without elastic net regularisation. Chronological analysis was performed by examining each patient's journey timepoint with reference to symptom onset. RESULTS: The mortality rate for 369 patients included was 18.9%. Patients treated conservatively, endoscopically, surgically, or combined approaches had mortality rates of 24.1%, 23.7%, 8.7%, and 18.2%, respectively. The predictive variables for mortality were Charlson comorbidity index, haemoglobin count, leucocyte count, creatinine levels, cause of perforation, presence of cancer, hospital transfer, CT findings, whether a contrast swallow was performed, and intervention type. Stepwise interval model showed that time to diagnosis was the most significant contributor to mortality. CONCLUSIONS: Non-surgical strategies have better outcomes and may be preferred in selected cohorts to manage perforations. Outcomes can be significantly improved through better risk-stratification based on afore-mentioned modifiable risk factors.

Journal article

Markar SR, Menon N, Guidozzi N, Kontouli K-M, Mavridis D, Andreou A, Berlth F, Bonavina L, Cushieri A, Fourie L, Gossage J, Gronnier C, Hazebroek EJ, Krishnadath S, Low DE, McCord M, Pouw RE, Watson DI, Carrano FM, Ortenzi M, Antoniou SAet al., 2023, EAES Multidisciplinary Rapid Guideline: systematic review, meta-analysis, GRADE assessment and evidence-informed recommendations on the surgical management of paraesophageal hernias., Surg Endosc, Vol: 37, Pages: 9013-9029

BACKGROUND: New evidence has emerged since latest guidelines on the management of paraesophageal hernia, and guideline development methodology has evolved. Members of the European Association for Endoscopic Surgery have prioritized the management of paraesophageal hernia to be addressed by pertinent recommendations. OBJECTIVE: To develop evidence-informed clinical practice recommendations on paraesophageal hernias, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: We performed three systematic reviews, and we summarized and appraised the certainty of the evidence using the GRADE methodology. A panel of general and upper gastrointestinal surgeons, gastroenterologists and a patient advocate discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost and use of resources, moderated by a Guidelines International Network-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests surgery over conservative management for asymptomatic/minimally symptomatic paraesophageal hernias (conditional recommendation), and recommends conservative management over surgery for asymptomatic/minimally symptomatic paraesophageal hernias in frail patients (strong recommendation). Further, the panel suggests mesh over sutures for hiatal closure in paraesophageal hernia repair, fundoplication over gastropexy in elective paraesophageal hernia repair, and gastropexy over fundoplication in patients who have cardiopulmonary instability and require emergency paraesophageal hernia repair (conditional recommendation). A strong recommendation means that the proposed course of action is appropriate for the vast majority of patients. A conditional recommendation means that most patients would opt for the proposed course of action, and joint d

Journal article

Guidozzi N, Menon N, Chidambaram S, Markar SRet al., 2023, The role of artificial intelligence in the endoscopic diagnosis of esophageal cancer: a systematic review and meta-analysis., Dis Esophagus, Vol: 36

Early detection of esophageal cancer is limited by accurate endoscopic diagnosis of subtle macroscopic lesions. Endoscopic interpretation is subject to expertise, diagnostic skill, and thus human error. Artificial intelligence (AI) in endoscopy is increasingly bridging this gap. This systematic review and meta-analysis consolidate the evidence on the use of AI in the endoscopic diagnosis of esophageal cancer. The systematic review was carried out using Pubmed, MEDLINE and Ovid EMBASE databases and articles on the role of AI in the endoscopic diagnosis of esophageal cancer management were included. A meta-analysis was also performed. Fourteen studies (1590 patients) assessed the use of AI in endoscopic diagnosis of esophageal squamous cell carcinoma-the pooled sensitivity and specificity were 91.2% (84.3-95.2%) and 80% (64.3-89.9%). Nine studies (478 patients) assessed AI capabilities of diagnosing esophageal adenocarcinoma with the pooled sensitivity and specificity of 93.1% (86.8-96.4) and 86.9% (81.7-90.7). The remaining studies formed the qualitative summary. AI technology, as an adjunct to endoscopy, can assist in accurate, early detection of esophageal malignancy. It has shown superior results to endoscopists alone in identifying early cancer and assessing depth of tumor invasion, with the added benefit of not requiring a specialized skill set. Despite promising results, the application in real-time endoscopy is limited, and further multicenter trials are required to accurately assess its use in routine practice.

Journal article

Chidambaram S, Owen R, Sgromo B, Chmura M, Kisiel A, Evans R, Griffiths EA, Castoro C, Gronnier C, MaoAwyes MA, Gutschow CA, Piessen G, Degisors S, Alvieri R, Feldman H, Capovilla G, Grimminger PP, Han S, Low DE, Moore J, Gossage J, Voeten D, Gisbertz SS, Ruurda J, van Hillegersberg R, D'Journo XB, Chmelo J, Phillips AW, Rosati R, Hanna GB, Maynard N, Hofstetter W, Ferri L, Berge Henegouwen MI, Markar SRet al., 2023, Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study., Ann Surg, Vol: 278, Pages: 701-708

OBJECTIVE: To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND: CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS: This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS: A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.

Journal article

Elliott JA, Klevebro F, Mantziari S, Markar SR, Goense L, Johar A, Lagergren P, Zaninotto G, van Hillegersberg R, van Berge Henegouwen MI, Schäfer M, Nilsson M, Hanna GB, Reynolds JV, ENSURE Study Groupet al., 2023, Neoadjuvant Chemoradiotherapy Versus Chemotherapy for the Treatment of Locally Advanced Esophageal Adenocarcinoma in the European Multicenter ENSURE Study., Ann Surg, Vol: 278, Pages: 692-700

OBJECTIVE: This study aimed to compare clinicopathologic, oncologic, and health-related quality of life (HRQL) outcomes following neoadjuvant chemoradiation (nCRT) and chemotherapy (nCT) in the ENSURE international multicenter study. BACKGROUND: nCT and nCRT are the standards of care for locally advanced esophageal cancer (LAEC) treated with curative intent. However, no published randomized controlled trial to date has demonstrated the superiority of either approach. METHODS: ENSURE is an international multicenter study of consecutive patients undergoing surgery for LAEC (2009-2015) across 20 high-volume centers (NCT03461341). The primary outcome measure was overall survival (OS), secondary outcomes included histopathologic response, recurrence pattern, oncologic outcome, and HRQL in survivorship. RESULTS: A total of 2211 patients were studied (48% nCT, 52% nCRT). pCR was observed in 4.9% and 14.7% ( P <0.001), with R0 in 78.2% and 94.2% ( P <0.001) post nCT and nCRT, respectively. Postoperative morbidity was equivalent, but in-hospital mortality was independently increased [hazard ratio (HR)=2.73, 95% CI: 1.43-5.21, P= 0.002] following nCRT versus nCT. Probability of local recurrence was reduced (odds ratio=0.71, 95% CI: 0.54-0.93, P =0.012), and distant recurrence-free survival time reduced (HR=1.18, 95% CI: 1.02-1.37, P =0.023) after nCRT versus nCT, with no difference in OS among all patients (HR=1.10, 95% CI: 0.98-1.25, P =0.113). On subgroup analysis, patients who underwent R0 resection following nCT as compared with nCRT had improved OS (median: 60.7 months, 95% CI: 49.5-71.8 vs 40.8 months, 95% CI: 42.8-53.4, P <0.001). CONCLUSIONS: In this European multicenter study, nCRT compared with nCT was associated with reduced probability of local recurrence but reduced distant recurrence-free survival for patients with LAEC, without differences in OS. These data support tailored patient-specific decision-making in the overall approach to achieving optimum o

Journal article

Geraedts TCM, Weijs TJ, Berkelmans GHK, Fransen LFC, Kouwenhoven EA, van Det MJ, Nilsson M, Lagarde SM, van Hillegersberg R, Markar SR, Nieuwenhuijzen GAP, Luyer MDPet al., 2023, Long-Term Survival Associated with Direct Oral Feeding Following Minimally Invasive Esophagectomy: Results from a Randomized Controlled Trial (NUTRIENT II), Cancers, Vol: 15

Advancements in perioperative care have improved postoperative morbidity and recovery after esophagectomy. The direct start of oral intake can also enhance short-term outcomes following minimally invasive Ivor Lewis esophagectomy (MIE-IL). Subsequently, short-term outcomes may affect long-term survival. This planned sub-study of the NUTRIENT II trial, a multicenter randomized controlled trial, investigated the long-term survival of direct versus delayed oral feeding following MIE-IL. The outcomes included 3- and 5-year overall survival (OS) and disease-free survival (DFS), and the influence of complications and caloric intake on OS. After excluding cases of 90-day mortality, 145 participants were analyzed. Of these, 63 patients (43.4%) received direct oral feeding. At 3 years, OS was significantly better in the direct oral feeding group (p = 0.027), but not at 5 years (p = 0.115). Moreover, 5-year DFS was significantly better in the direct oral feeding group (p = 0.047) and a trend towards improved DFS was shown at 3 years (p = 0.079). Postoperative complications and caloric intake on day 5 did not impact OS. The results of this study show a tendency of improved 3-year OS and 5-year DFS, suggesting a potential long-term survival benefit in patients receiving direct oral feeding after esophagectomy. However, the findings should be further explored in larger future trials.

Journal article

Menon N, Guidozzi N, Chidambaram S, Puri A, Sounderajah V, Ferri L, Griffiths EA, Low D, Maynard N, Mueller C, Pera M, van Berge Henegouwen M, Watson D, Zaininotto G, Hanna GB, Markar SRet al., 2023, Research protocol for the Paraesophageal hernia symptom tool, a prospective multi-center cohort study to identify the need and threshold for surgery and assess the symptom response to surgery, DISEASES OF THE ESOPHAGUS, Vol: 36, ISSN: 1120-8694

Journal article

ARROW Study Group, Writing Group, Walker R, Currie A, Wiggins T, Markar SR, Blencowe NS, Underwood T, Hollyman Met al., 2023, Results of the ARROW survey of anti-reflux practice in the United Kingdom., Dis Esophagus, Vol: 36

Gastro-esophageal reflux disease (GERD) is a common, significant health burden. United Kingdom guidance states that surgery should be considered for patients with a diagnosis of GERD not suitable for long-term acid suppression. There is no consensus on many aspects of patient pathways and optimal surgical technique, and an absence of information on how patients are currently selected for surgery. Further detail on the delivery of anti-reflux surgery (ARS) is required. A United Kingdom-wide survey was designed to gather surgeon opinion regarding pre-, peri- and post-operative practice of ARS. Responses were received from 155 surgeons at 57 institutions. Most agreed that endoscopy (99%), 24-hour pH monitoring (83%) and esophageal manometry (83%) were essential investigations prior to surgery. Of 57 units, 30 (53%) had access to a multidisciplinary team to discuss cases; case-loads were higher in those units (median 50 vs. 30, P < 0.024). The most popular form of fundoplication was a Nissen posterior 360° (75% of surgeons), followed by a posterior 270° Toupet (48%). Only seven surgeons stated they had no upper limit of body mass index prior to surgery. A total of 46% of respondents maintain a database of their practice and less than a fifth routinely record quality of life scores before (19%) or after (14%) surgery. While there are areas of consensus, a lack of evidence to support workup, intervention and outcome evaluation is reflected in the variability of practice. ARS patients are not receiving the same level of evidence-based care as other patient groups.

Journal article

Puri A, Steven S, Markar SR, Boyle Net al., 2023, Longer-term outcomes of gastroesophageal reflux disease treated with magnetic sphincter augmentation., Dis Esophagus, Vol: 36

Surgical intervention for gastroesophageal reflux disease (GERD) has historically been limited to fundoplication. Magnetic sphincter augmentation (MSA) is a less invasive alternative that was introduced 15 years ago, and it may have a superior side-effect profile. To date, however, there has been just a single published study reporting outcomes in a UK population. This study reports quality-of-life (QOL) outcomes and antacid use in patients undergoing MSA, with a particular focus on postoperative symptoms and those with severe reflux. A single-center cohort study was carried out to assess the QOL outcomes and report long-term safety outcomes in patients undergoing MSA. GERD-health-related quality of life (GERD-HRQL) and Reflux Symptom Index (RSI) scores were collected preoperatively, and immediately postoperatively, at 1-, 2-, 3-, and 5-year follow-up time points. All patients underwent preoperative esophagogastroduodenoscopy, impedance, and manometry. Two hundred and two patients underwent laparoscopic MSA over 9 years. The median preoperative GERD-HRQL score was 31, and the median RSI score was 17. There was a reduction in all scores from preoperative values to each time point, which was sustained at 5-year follow-up; 13% of patients had a preoperative DeMeester score of >50, and their median preoperative GERD-HRQL and RSI scores were 32 and 15.5, respectively. These were reduced to 0 at the most recent follow-up. There was a significant reduction in antacid use at all postoperative time points. Postoperative dilatation was necessary in 7.4% of patients, and the device was removed in 1.4%. Erosion occurred in no patients. MSA is safe and effective at reducing symptom burden and improving QOL scores in patients with both esophageal and laryngopharyngeal symptoms, including those with severe reflux.

Journal article

Markar SR, Guazzelli A, Taylor A, Jones LL, Dutton S, Jogarah V, Brittain C, Maynard N, Cromwell D, Landeiro F, Underwood T, Lagergren J, Gleeson F, Moss A, Crosby Tet al., 2023, Protocol for open-label randomized clinical trial of intensive surveillance versus standard postoperative follow-up in patients undergoing surgical resection for oesophageal and gastric cancer., Br J Surg, Vol: 110, Pages: 1359-1360

Journal article

Hanna L, Jha R, Sounderajah V, Markar S, Gibbs Ret al., 2023, Patient Reported Outcome Measures Used to Assess Quality of Life in Aortic Dissection: a Systematic Scoping Review using COSMIN Methodology, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 66, Pages: 343-350, ISSN: 1078-5884

Journal article

Kauppila JH, Markar S, Santoni G, Holmberg D, Lagergren Jet al., 2023, Temporal Changes in Obesity-Related Medication After Bariatric Surgery vs No Surgery for Obesity., JAMA Surg, Vol: 158, Pages: 817-823

IMPORTANCE: Bariatric surgery can resolve hyperlipidemia, cardiovascular disease, and diabetes, but the long-term postoperative trajectories of medications for these conditions are unknown. OBJECTIVE: To clarify the long-term use of lipid-lowering, cardiovascular, and antidiabetic medication after bariatric surgery compared with no surgery for morbid obesity. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study took place in Sweden (2005-2020) and Finland (1995-2018) and included individuals diagnosed with obesity. Analysis took place between July 2021 and January 2022. EXPOSURES: Bariatric surgery (gastric bypass or sleeve gastrectomy) patients using lipid-lowering, cardiovascular, or antidiabetic medication were compared with 5 times as many control patients with an obesity diagnosis treated with no surgery, matched for country, age, sex, calendar year, and medication use. MAIN OUTCOMES AND MEASURES: Proportions with 95% CIs of lipid-lowering, cardiovascular, or antidiabetic medication. RESULTS: A total of 26 396 patients underwent bariatric surgery (with gastric bypass or sleeve gastrectomy) (17 521 [66.4%] women; median [IQR] age, 50 [43-56] years) and 131 980 matched control patients (87 605 [66.4%%] women; median [IQR] age, 50 [43-56] years) were included. The proportion of lipid-lowering medication after bariatric surgery decreased from 20.3% (95% CI, 20.2%-20.5%) at baseline to 12.9% (95% CI, 12.7%-13.0%) after 2 years and 17.6% (95% CI, 13.3%-21.8%) after 15 years, while it increased in the no surgery group from 21.0% (95% CI, 20.9%-21.1%) at baseline to 44.6% (95% CI, 41.7%-47.5%) after 15 years. Cardiovascular medications were used by 60.2% (95% CI, 60.0%-60.5%) of bariatric surgery patients at baseline, decreased to 43.2% (95% CI, 42.9%-43.4%) after 2 years, and increased to 74.6% (95% CI, 65.8%-83.4%) after 15 years, while it increased in the no surgery group from 54.4% (95% CI, 54.3%-54.5%) at baseline to 83.3% (95% CI, 79.3%-87.3%) af

Journal article

Patel K, Sounderajah V, Hanna L, Acharya A, Chidambaram S, Normahani P, Markar SR, Bicknell Cet al., 2023, Quantifying the burden of survivorship associated with infrarenal abdominal aortic aneurysms, JOURNAL OF VASCULAR SURGERY, Vol: 78, Pages: 549-+, ISSN: 0741-5214

Journal article

Casey P, Gossage JA, Ford K, Huddy F, Owen K, Harvey A, Markar S, McLaughlin J, Sultan J, NONA steering committeeet al., 2023, The current landscape of nutrition care in oesophageal and gastric cancer - insights from the national oesophagogastric nutrition audit (NONA) survey., Clin Nutr ESPEN, Vol: 56, Pages: 87-93

BACKGROUND AND AIMS: Specialist nutritional support is important during treatment for oesophagogastric (OG) cancer yet current practice remains unstandardised across the UK. The National Oesophagogastric Nutrition Audit (NONA) aimed to describe the current landscape of OG dietetic services in the UK and Ireland, with a specific focus on resource allocation, barriers to dietetic support, and the provision of support throughout the cancer pathway. METHODS: Tertiary cancer units, secondary care, and community services across the UK and Ireland were invited to complete a 28-point electronic questionnaire. Team leaders and senior specialist OG dietitians were the target respondents. All data points were peer-reviewed, piloted, and revised by the NONA steering committee before distribution. Data points covered a range of areas related to resources, skill mix, provision of support throughout the cancer pathway, and involvement with national audit and research. RESULTS: Complete responses were received from 50 individual units (tertiary surgical units, n = 35 and tertiary oncology units, n = 10). Secondary care and community services were underrepresented (n = 5). Of the units proving tertiary cancer care, the majority (77%) agreed or strongly agreed they were able to provide adequate nutritional care in the post-operative period. However, confidence dropped significantly in the early diagnostic phase and in the neoadjuvant period, with 52% and 67% of tertiary units disagreeing that they could provide adequate dietetic support during these parts of the cancer pathway, respectively. Inadequate funding, understaffing, and the prioritisation of inpatients were commonly reported barriers. There was significant variation in practice regarding nutritional assessment, service structure, and staffing resource allocation across specialist units. CONCLUSION: The NONA survey provides a 'real-world' landscape of nutritional care for patients with OG cancer

Journal article

Talavera-Urquijo E, Gantxegi A, Garbarino GM, Capovilla G, van Boxel GI, Grimminger PP, Luyer MD, Markar SR, Svendsen LB, van Hillegersberg Ret al., 2023, ESDE-MIE fellowship: a descriptive analysis of the first experiences., Dis Esophagus, Vol: 36

Esophageal resection is a high-risk and technically demanding procedure, with a long proficiency-gain curve. The European Society Diseases of the Esophagus (ESDE)-Minimally Invasive Esophagectomy (MIE) training program was launched in 2018 for European surgeons willing to train and to begin a career undertaking MIE. The aim of this study was to evaluate the first experience of the ESDE-MIE fellowship and relate this to the initially predetermined core principles and objectives of the program. Between October 2021 and May 2022, the participating fellows, in collaboration with the ESDE Educational Committee, initiated a survey to assess the outcome and experience of these fellowships. Data from each individual fellowship were analysed and reported in a descriptive manner. Between 2018 and 2022, in total, five fellows have completed the ESDE-MIE fellowship program. Despite the COVID-19 outbreak just the year after its launch, predetermined clinical and research goals were achieved in all cases. Each of the fellows were able to assist in a median of 40 (IQR 27-69) MIE and/or Robot assisted (RA)MIE procedures, of a total median of 115 (IQR 83-123) attended Upper GI cases. After the fellowship, MIE has been fully adopted by the fellows who returned to their home institutions as Upper GI surgeons. The fellowship was concluded by the European Union of Medical Specialists (UEMS) Multidisciplinary Joint Committee (MJC) certification in Upper GI Surgery, which was successfully obtained by all who took part. Based on the experience of the first five fellows, the ESDE-MIE training fellowship meets with the expected needs even despite the COVID-19 outbreak in 2019. Furthermore, these fellows have returned home and integrated MIE into their independent surgical practice, affirming the ability of this program to train the next generation of MIE surgeons, even in the most challenging of circumstances.

Journal article

Tankel J, Markar S, van Berge Henegouwen M, Ferri L, Cools-Lartigue Jet al., 2023, Endoscopic surveillance in hereditary diffuse gastric cancer., Lancet Oncol, Vol: 24

Journal article

Chidambaram S, Guiral DC, Markar SR, 2023, Novel Multi-Modal Therapies and Their Prognostic Potential in Gastric Cancer., Cancers (Basel), Vol: 15, ISSN: 2072-6694

BACKGROUND: Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. METHODS: A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. RESULTS: The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. CONCLUSIONS: Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection.

Journal article

Gujjuri RM, Clarke JA, Elliott JA, Rahman SV, Reynolds JB, Hanna GR, Markar S, ENSURE SGet al., 2023, Predicting Long-term Survival and Time-to-recurrence After Esophagectomy in Patients With Esophageal Cancer Development and Validation of a Multivariate Prediction Model, ANNALS OF SURGERY, Vol: 277, Pages: 971-978, ISSN: 0003-4932

Journal article

Asplund JPU, Mackenzie HA, Markar SR, Lagergren JHFet al., 2023, Original Research Surgeon proficiency gain and survival after gastrectomy for gastric adenocarcinoma: A population-based cohort study, EUROPEAN JOURNAL OF CANCER, Vol: 186, Pages: 91-97, ISSN: 0959-8049

Journal article

Gerdes S, Schoppmann SF, Bonavina L, Boyle N, Mueller-Stich BP, Gutschow CA, Gisbertz SS, Kockerling F, Lehmann TG, Lorenz D, Granderath FA, Rosati R, Wullstein C, Lundell L, Cheong E, Nafteux P, Olmi S, Monig S, Biebl M, Leers J, Zehetner J, Kristo I, Berrisford RG, Skrobic OM, Simic AP, Pera M, Grimminger PP, Gockel I, Zarras K, Nieuwenhuijs VB, Gossage JA, Henegouwen MIVB, Stein HJ, Markar SR, Hueting WE, Targarona EM, Johansson J, Macaulay GD, Wijnhoven BPL, Benedix F, Attwood SE, Hoelscher AH, Priego P, Fuchs K-H, Luyer MDP, Griffiths EA, Sovik TT, Theodorou D, Sgromo B, Salo JA, Singhal R, Thorell A, Zaninotto G, Itenc M, D'journo XB, Fullarton GM, Horbach Tet al., 2023, Management of paraesophageal hiatus hernia: recommendations following a European expert Delphi consensus, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 37, Pages: 4555-4565, ISSN: 0930-2794

Journal article

Menon N, Guidozzi N, Chidambaram S, Markar SRet al., 2023, Performance of radiomics-based artificial intelligence systems in the diagnosis and prediction of treatment response and survival in esophageal cancer: a systematic review and meta-analysis of diagnostic accuracy., Dis Esophagus, Vol: 36

Radiomics can interpret radiological images with more detail and in less time compared to the human eye. Some challenges in managing esophageal cancer can be addressed by incorporating radiomics into image interpretation, treatment planning, and predicting response and survival. This systematic review and meta-analysis provides a summary of the evidence of radiomics in esophageal cancer. The systematic review was carried out using Pubmed, MEDLINE, and Ovid EMBASE databases-articles describing radiomics in esophageal cancer were included. A meta-analysis was also performed; 50 studies were included. For the assessment of treatment response using 18F-FDG PET/computed tomography (CT) scans, seven studies (443 patients) were included in the meta-analysis. The pooled sensitivity and specificity were 86.5% (81.1-90.6) and 87.1% (78.0-92.8). For the assessment of treatment response using CT scans, five studies (625 patients) were included in the meta-analysis, with a pooled sensitivity and specificity of 86.7% (81.4-90.7) and 76.1% (69.9-81.4). The remaining 37 studies formed the qualitative review, discussing radiomics in diagnosis, radiotherapy planning, and survival prediction. This review explores the wide-ranging possibilities of radiomics in esophageal cancer management. The sensitivities of 18F-FDG PET/CT scans and CT scans are comparable, but 18F-FDG PET/CT scans have improved specificity for AI-based prediction of treatment response. Models integrating clinical and radiomic features facilitate diagnosis and survival prediction. More research is required into comparing models and conducting large-scale studies to build a robust evidence base.

Journal article

Kamarajah SK, Markar SR, Low D, Phillips AWet al., 2023, Prognostic implications of the extent of downstaging after neoadjuvant therapy for oesophageal adenocarcinoma and oesophageal squamous cell carcinoma., BJS Open, Vol: 7

BACKGROUND: There are few data evaluating the extent of downstaging in patients with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma and the difference in outcomes for a similar pathological stage in neoadjuvant-naive patients. The aim of this study was to characterize the prognostic value of downstaging extent in patients receiving neoadjuvant therapy for oesophageal cancer. METHODS: Oesophageal adenocarcinoma and oesophageal squamous cell carcinoma patients receiving either neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy between 2004 and 2017 were identified from the National Cancer Database. The extent of downstaging was defined as the extent of migration between groups (for example stage IVa to IIIb = one stage). Cox multivariable regression was used to produce adjusted models for downstaging extent. RESULTS: Of 13 594 patients, 11 355 with oesophageal adenocarcinoma and 2239 with oesophageal squamous cell carcinoma were included. In oesophageal adenocarcinoma, patients with downstaged disease by three or more stages (hazards ratio (HR) 0.40, 95 per cent c.i. 0.36 to 0.44, P < 0.001), two stages (HR 0.43, 95 per cent c.i. 0.39 to 0.48, P < 0.001), or one stage (HR 0.57, 95 per cent c.i. 0.52 to 0.62, P < 0.001) had significantly longer survival than those with upstaged disease in adjusted analyses. In oesophageal squamous cell carcinoma, patients with downstaged disease by three or more stages had significantly longer survival than those with less downstaged disease, no change, or upstaged disease. Patients with downstaged disease by three or more stages (HR 0.55, 95 per cent c.i. 0.43 to 0.71, P < 0.001), two stages (HR 0.58, 95 per cent c.i. 0.46 to 0.73, P < 0.001), or one stage (HR 0.69, 95 per cent c.i. 0.55 to 0.86, P = 0.001) had significantly longer survival than those with upstaged disease in adjusted analyses. CONCLUSION: The extent of downstaging is an important prognosticator, whereas the optimal neoadjuvan

Journal article

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