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
to

319 results found

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., Eur J Vasc Endovasc Surg, Vol: 66, Pages: 343-350

OBJECTIVE: To systematically identify all patient reported outcome measures (PROMs) (quality of life [QOL] instruments or other instrument/methodology) that have been used to date in aortic dissection (AD) and to explore how well these instruments evaluate QOL according to the Consensus based Standards for the selection of health Measurement Instruments (COSMIN) methodology or guideline. DATA SOURCES: Embase, MEDLINE, PsycINFO, CINAHL, and Cochrane Library were search on 1st July 2022. REVIEW METHODS: This scoping review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and the COSMIN guidelines for performing systematic reviews of validated PROMs. Studies that reported on any aspect or domain of QOL using a PROM or other instrument or methodology on AD were included. Data synthesis, including psychometric property analysis and risk of bias assessment were performed according to COSMIN guidelines. RESULTS: Forty-five studies, published between 1994 and 2021 reporting on 5 874 patients (mean age 63 years, 70.6% male), were included. A total of 39 PROMs were used, and three studies used semi-structured interviews. The majority (69%) of studies were in patients with type A aortic dissection (TAAD). The most common PROM used was the SF-36 (51%). Six studies evaluated one or more psychometric properties of a PROM. Only one of these studies was specifically designed as a validation study. No study reported on content validity. Internal consistency was the most evaluated psychometric property. No study evaluated all the psychometric properties according to COSMIN methodology. The methodological quality used to assess these PROMs was judged to be adequate or very good. CONCLUSION: This review highlights the heterogeneity of PROMs or methods used to determine QOL in AD patients. The lack of research regarding a comprehensive evaluation of the psychometric properties of a PROM used in

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

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

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., J Vasc Surg, Vol: 78, Pages: 549-557.e23

OBJECTIVES: Survivorship encompasses the physical, psychological, social, functional, and economic experience of a living with a chronic condition for both the patient and their caregiver. It is made up of nine distinct domains and remains understudied in nononcological pathologies, including infrarenal abdominal aortic aneurysmal disease (AAA). This review aims to quantify the extent to which existing AAA literature addresses the burden of survivorship. METHODS: The MEDLINE, EMBASE, and PsychINFO databases were searched from 1989 through September 2022. Randomized controlled trials, observational studies, and case series were included. Eligible studies had to detail outcomes related to survivorship in patients with AAA. Owing to the heterogeneity between studies and outcomes, no meta-analysis was conducted. Study quality was assessed with specific risk of bias tools. RESULTS: A total of 158 studies were included. Of these, only five (treatment complications, physical functioning, comorbidities, caregivers, and mental health) of the nine domains of survivorship have been studied previously. The available evidence is of variable quality; most studies display a moderate to high risk of bias, are of an observational study design, are based within a limited number of countries, and consist of an insufficient follow-up period. The most frequent complication after EVAR was endoleak. EVAR is associated with poorer long-term outcomes compared with open surgical repair in most studies retrieved. EVAR showed better outcomes in regard to physical functioning in the short term, but this advantage was lost in the long term. The most common comorbidity studied was obesity. No significant differences were found between open surgical repair and EVAR in terms of impact on caregivers. Depression is associated with various comorbidities and increased the risk of a nonhospital discharge. CONCLUSIONS: This review highlights the absence of robust evidence regarding survivorship in AAA. A

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

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

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

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

Asplund JPU, Mackenzie HA, Markar SR, Lagergren JHFet al., 2023, Surgeon proficiency gain and survival after gastrectomy for gastric adenocarcinoma: A population-based cohort study., Eur J Cancer, Vol: 186, Pages: 91-97

OBJECTIVE: Quality of surgery is essential for survival in gastric adenocarcinoma, but studies examining surgeons' proficiency gain of gastrectomies are scarce. This study aimed to reveal potential proficiency gain curves for surgeons operating patients with gastric cancer. METHODS: Population-based cohort study of patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2020. Data were retrieved from national registries and medical records. Risk prediction models were used to calculate outcome probabilities, and risk-adjusted cumulative sum curves were plotted to assess differences (change points) between observed and expected outcomes. The main outcome was long-term (>3-5 years) all-cause mortality after surgery. Secondary outcomes were all-cause mortality within 30 days, 31-90 days, 91 days to 1 year and>1-3 years of surgery, resection margin status, and lymph node yield. RESULTS: The study included 261 surgeons and 1636 patients. The>3- to 5-year mortality was improved after 20 cases, and decreased from 12.4% before to 8.6% after this change point (p = 0.027). Change points were suggested, but not statistically significant, after 22 cases for 30-day mortality, 28 cases for 31- to 90-day mortality, 9 cases for 91-day to 1-year mortality, and 10 cases for>1- to 3-year all-cause mortality. There were statistically significant improvements in tumour-free resection margins after 28 cases (p < 0.005) and greater lymph node yield after 13 cases (p < 0.001). CONCLUSIONS: This study reveals proficiency gain curves regarding long-term survival, resection margin status, and lymph node yield in gastrectomy for gastric adenocarcinoma, and that at least 20 gastrectomies should be conducted with experienced support before doing these operations independently.

Journal article

Gerdes S, Schoppmann SF, Bonavina L, Boyle N, Müller-Stich BP, Gutschow CA, Hiatus Hernia Delphi Collaborative Groupet al., 2023, Management of paraesophageal hiatus hernia: recommendations following a European expert Delphi consensus., Surg Endosc, Vol: 37, Pages: 4555-4565

AIMS: There is considerable controversy regarding optimal management of patients with paraesophageal hiatus hernia (pHH). This survey aims at identifying recommended strategies for work-up, surgical therapy, and postoperative follow-up using Delphi methodology. METHODS: We conducted a 2-round, 33-question, web-based Delphi survey on perioperative management (preoperative work-up, surgical procedure and follow-up) of non-revisional, elective pHH among European surgeons with expertise in upper-GI. Responses were graded on a 5-point Likert scale and analyzed using descriptive statistics. Items from the questionnaire were defined as "recommended" or "discouraged" if positive or negative concordance among participants was > 75%. Items with lower concordance levels were labelled "acceptable" (neither recommended nor discouraged). RESULTS: Seventy-two surgeons with a median (IQR) experience of 23 (14-30) years from 17 European countries participated (response rate 60%). The annual median (IQR) individual and institutional caseload was 25 (15-36) and 40 (28-60) pHH-surgeries, respectively. After Delphi round 2, "recommended" strategies were defined for preoperative work-up (endoscopy), indication for surgery (typical symptoms and/or chronic anemia), surgical dissection (hernia sac dissection and resection, preservation of the vagal nerves, crural fascia and pleura, resection of retrocardial lipoma) and reconstruction (posterior crurorrhaphy with single stitches, lower esophageal sphincter augmentation (Nissen or Toupet), and postoperative follow-up (contrast radiography). In addition, we identified "discouraged" strategies for preoperative work-up (endosonography), and surgical reconstruction (crurorrhaphy with running sutures, tension-free hiatus repair with mesh only). In contrast, many items from the questionnaire including most details of mesh augmentation (indication, material, shape, placement, and fix

Journal article

Gujjuri RR, Clarke JM, Elliott JA, Rahman SA, Reynolds JV, Hanna GB, Markar SR, ENSURE Group Studyet 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., Ann Surg, Vol: 277, Pages: 971-978

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

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

Kroese TE, van Laarhoven HWM, Schoppman SF, Deseyne PRAJ, van Cutsem E, Haustermans K, Nafteux P, Thomas M, Obermannova R, Mortensen HR, Nordsmark M, Pfeiffer P, Elme A, Adenis A, Piessen G, Bruns CJ, Lordick F, Gockel I, Moehler M, Gani C, Liakakos T, Reynolds J, Morganti AG, Rosati R, Castoro C, Cellini F, D'Ugo D, Roviello F, Bencivenga M, de Manzoni G, van Berge Henegouwen MI, Hulshof MCCM, van Dieren J, Vollebergh M, van Sandick JW, Jeene P, Muijs CT, Slingerland M, Voncken FEM, Hartgrink H, Creemers G-J, van der Sangen MJC, Nieuwenhuijzen G, Berbee M, Verheij M, Wijnhoven B, Beerepoot LV, Mohammad NH, Mook S, Ruurda JP, Kolodziejczyk P, Polkowski WP, Wyrwicz L, Alsina M, Pera M, Kanonnikoff TF, Cervantes A, Nilsson M, Monig S, Wagner AD, Guckenberger M, Griffiths EA, Smyth E, Hanna GB, Markar S, Chaudry MA, Hawkins MA, Cheong E, van Hillegersberg R, van Rossum PSN, OMEC collaboratorset al., 2023, Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe., Eur J Cancer, Vol: 185, Pages: 28-39

BACKGROUND: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement)

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

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. CONCLUSION: 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

Hall L, Halle-Smith J, Evans R, Toogood G, Wiggins T, Markar SR, Kapoulas S, Super P, Tucker O, McKay SCet al., 2023, Ursodeoxycholic acid in the management of symptomatic gallstone disease: systematic review and clinician survey, BJS Open, Vol: 7

Background: Symptomatic gallstones are common. Ursodeoxycholic acid (UDCA) is a bile acid that dissolves gallstones. There is increasing interest in UDCA for symptomatic gallstones, particularly in those unfit for surgery. Method: A UK clinician survey of use and opinions about UDCA in symptomatic gallstones was performed, assessing clinicians' beliefs and perceptions of UDCA effectiveness. A systematic review was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, and Embase databases were searched for studies of UDCA for symptomatic gallstones (key terms included 'ursodeoxycholic acid'; 'UDCA'; 'biliary pain'; and 'biliary colic'). Information was assessed by two authors, including bias assessment, with independent review of conflicts. Results: Overall, 102 clinicians completed the survey, and 42 per cent had previous experience of using UDCA. Survey responses demonstrated clinical equipoise surrounding the benefit of UDCA for the management of symptomatic gallstones, with no clear consensus for benefit or non-benefit; however, 95 per cent would start using UDCA if there was a randomized clinical trial (RCT) demonstrating a benefit. Eight studies were included in the review: four RCTs, three prospective studies, and one retrospective study. Seven of eight studies were favourable of UDCA for biliary pain. Outcomes and follow-up times were heterogenous, as well as comparator type, with only four of eight studies comparing with placebo. Conclusion: Evidence for UDCA in symptomatic gallstones is scarce and heterogenous. Clinicians currently managing symptomatic gallstone disease are largely unaware of the benefit of UDCA, and there is clinical equipoise surrounding the benefit of UDCA. Level 1 evidence is required by clinicians to support UDCA use in the future.

Journal article

Wen Q, Myridakis A, Boshier PR, Zuffa S, Belluomo I, Parker AG, Chin S-T, Hakim S, Markar SR, Hanna GBet al., 2023, A complete pipeline for untargeted urinary volatolomic profiling with sorptive extraction and dual polar and nonpolar column methodologies coupled with gas chromatography time-of-flight mass spectrometry., Analytical Chemistry, Vol: 95, Pages: 758-765, ISSN: 0003-2700

Volatolomics offers an opportunity for noninvasive detection and monitoring of human disease. While gas chromatography-mass spectrometry (GC-MS) remains the technique of choice for analyzing volatile organic compounds (VOCs), barriers to wider adoption in clinical practice still exist, including: sample preparation and introduction techniques, VOC extraction, throughput, volatolome coverage, biological interpretation, and quality control (QC). Therefore, we developed a complete pipeline for untargeted urinary volatolomic profiling. We optimized a novel extraction technique using HiSorb sorptive extraction, which exhibited high analytical performance and throughput. We achieved a broader VOC coverage by using HiSorb coupled with a set of complementary chromatographic methods and time-of-flight mass spectrometry. Furthermore, we developed a data preprocessing strategy by evaluating internal standard normalization, batch correction, and we adopted strict QC measures including removal of nonlinearly responding, irreproducible, or contaminated metabolic features, ensuring the acquisition of high-quality data. The applicability of this pipeline was evaluated in a clinical cohort consisting of pancreatic ductal adenocarcinoma (PDAC) patients (n = 28) and controls (n = 33), identifying four urinary candidate biomarkers (2-pentanone, hexanal, 3-hexanone, and p-cymene), which can successfully discriminate the cancer and noncancer subjects. This study presents an optimized, high-throughput, and quality-controlled pipeline for untargeted urinary volatolomic profiling. Use of the pipeline to discriminate PDAC from control subjects provides proof of principal of its clinical utility and potential for application in future biomarker discovery studies.

Journal article

Antoniou SA, Florez ID, Markar S, Logullo P, López-Cano M, Silecchia G, Antoniou GA, Tsokani S, Mavridis D, Brouwers M, GAP Consortiumet al., 2023, Author Correction: AGREE-S: AGREE II extension for surgical interventions: appraisal instrument., Surg Endosc, Vol: 37

Journal article

Schuring N, Jezerskyte E, van Berge Henegouwen MI, Sprangers MAG, Lagergren P, Johar A, Markar SR, Gisbertz SS, LASER study groupet al., 2023, Influence of postoperative complications following esophagectomy for cancer on quality of life: A European multicenter study., Eur J Surg Oncol, Vol: 49, Pages: 97-105

INTRODUCTION: Postoperative complications following major surgery have been shown to be associated with reduced health-related quality of life (HRQL), and severe complications may have profound negative effects. This study aimed to examine whether long-term HRQL differs with the occurrence and severity of complications in a European multicenter prospective dataset of patients following esophagectomy for cancer. METHODS: Disease-free patients following esophagectomy for cancer between 2010 and 2016 from the LASER study were included. Patients completed the LASER, EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires >1 year following treatment. Long-term HRQL was compared between patients with and without postoperative complications, subgroup analysis was performed for severity of complications (no, minor [Clavien-Dindo I-II], severe [Clavien-Dindo ≥ III]), using univariable and multivariable regression. RESULTS: 645 patients were included: 283 patients with no, 207 with minor and 155 with severe complications. Significantly more dyspnea (QLQ-C30) was reported by patients with compared to patients without complications (differenceinmeans6.3). In subgroup analysis, patients with severe complications reported more dyspnea (difference in means 8.3) than patients with no complications. None of the differences were clinically relevant (difference in means ≥ 10 points). LASER-based low mood (OR2.3) was statistically different for minor versus severe complications. CONCLUSION: Comparable HRQL was found in patients with and without postoperative complications following esophagectomy for cancer, after a mean follow-up of 4.4 years. Furthermore, patients with different levels of severity of complications had comparable HRQL. The level of HRQL in esophageal cancer patients are more likely explained by the impact of the complex procedure of the esophagectomy itself.

Journal article

Leijonmarck W, Asplund J, Markar SR, Mattsson F, Lagergren Jet al., 2023, Weekday of gastrectomy and long-term survival in gastric adenocarcinoma., Eur J Surg Oncol, Vol: 49, Pages: 83-88

BACKGROUND: Cancer surgery conducted late during the working week might decrease long-term survival for some tumours. Studies on how weekday of gastrectomy influences long-term survival following gastric cancer are few and show conflicting results, which prompted the present investigation. METHODS: This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015, with follow-up throughout 2020. Associations between weekday of gastrectomy and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome) were analysed using multivariable Cox regression. The hazard ratios (HR) with 95% confidence intervals (CI) were adjusted for age, sex, education, comorbidity, pathological tumour stage, tumour sub-location, neoadjuvant therapy, annual surgeon volume of gastrectomy, and calendar year. RESULTS: Among 1678 patients, surgery on Thursday-Friday was not associated with any statistically significantly increased risk of 5-year all-cause mortality (HR 1.05, 95% CI 0.91-1.22) or 5-year disease-specific mortality (HR 1.04, 95% CI 0.89-1.23) compared to Monday-Wednesday. No associations were found when each weekday was analysed separately, with point estimates close to 1.00 (range 0.98-1.00) Monday-Thursday, but increased for Friday (HR 1.22, 95% CI 0.89-1.68) when fewer patients underwent surgery (4% of all). Stratified analyses by age, comorbidity, tumour stage, neoadjuvant therapy, surgeon volume, and tumour sub-location did not reveal any associations between weekday of surgery on Thursday-Friday compared with Monday-Wednesday and risk of 5-year all-cause mortality. CONCLUSIONS: Weekday of gastrectomy might not influence the 5-year survival in patients with gastric adenocarcinoma.

Journal article

Markar SR, Santoni G, Holmberg D, Kauppila JH, Lagergren Jet al., 2022, Bariatric surgery volume by hospital and long-term survival: population-based NordOSCo data, BRITISH JOURNAL OF SURGERY, Vol: 110, Pages: 177-182, ISSN: 0007-1323

Journal article

Cools-Lartigue J, Markar S, Mueller C, Hofstetter W, Nilsson M, Ilonen I, Soderstrom H, Rasanen J, Gisbertz S, Hanna GB, Elliott J, Reynolds J, Kisiel A, Griffiths E, Henegouwen MVB, Ferri Let al., 2022, An International Cohort Study of Prognosis Associated With Pathologically Complete Response Following Neoadjuvant Chemotherapy Versus Chemoradiotherapy of Surgical Treated Esophageal Adenocarcinoma, ANNALS OF SURGERY, Vol: 276, Pages: 799-805, ISSN: 0003-4932

Journal article

Schuring N, Markar SR, Hagens ERC, Jezerskyte E, Sprangers MAG, Lagergren P, Johar A, Gisbertz SS, Henegouwen MIVBet al., 2022, Health-related quality of life following neoadjuvant chemoradiotherapy versus perioperative chemotherapy and esophagectomy for esophageal cancer: a European multicenter study, DISEASES OF THE ESOPHAGUS, ISSN: 1120-8694

Journal article

Markar S, Andreou A, Bonavina L, Florez ID, Huo B, Kontouli K-M, Low DE, Mavridis D, Maynard N, Moss A, Pera M, Savarino E, Siersema P, Sifrim D, Watson DI, Zaninotto G, Antoniou SAet al., 2022, UEG and EAES rapid guideline: Update systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on surgical management of GERD, UNITED EUROPEAN GASTROENTEROLOGY JOURNAL, Vol: 10, Pages: 983-998, ISSN: 2050-6406

Journal article

Chidambaram S, Sounderajah V, Maynard N, Owen R, Markar SRet al., 2022, Evaluation of tumor regression by neoadjuvant chemotherapy regimens for esophageal adenocarcinoma: a systematic review and meta-analysis, DISEASES OF THE ESOPHAGUS, ISSN: 1120-8694

Journal article

Holmberg D, Santoni G, Kauppila JH, Markar SR, Lagergren Jet al., 2022, Long-term Survival After Sleeve Gastrectomy Versus Gastric Bypass in a Binational Cohort Study., Diabetes Care, Vol: 45, Pages: 1981-1986

OBJECTIVE: Bariatric surgery prolongs life expectancy in severely obese individuals, but it is uncertain which of the two dominating bariatric procedures, sleeve gastrectomy or gastric bypass, offers the best long-term survival. RESEARCH DESIGN AND METHODS: This was a population-based cohort study of primary laparoscopic sleeve gastrectomy compared with gastric bypass for obesity in Sweden and Finland between 1 January 2007 and 31 December 2020. The risk of all-cause mortality was calculated using multivariable Cox regression, providing hazard ratios (HRs) with 95% CIs adjusted for age, sex, hypertension, diabetes, Charlson comorbidity index, country, and calendar year. RESULTS: Among 61,503 patients (median age 42 years; 75.4% women), who contributed 415,712 person-years at risk (mean 6.8 person-years), 1,571 (2.6%) died during follow-up. Compared with patients who underwent gastric bypass (n = 51,891 [84.4%]), the sleeve gastrectomy group (n = 9,612 [15.6%]) had similar all-cause mortality during the entire study period (HR 0.98, 95% CI 0.81-1.20), but decreased all-cause mortality in more recent years (HR 0.72, 95% CI 0.54-0.97, from 2014 onward). Diabetes interacted statistically significantly with the type of bariatric surgery, with higher all-cause mortality after sleeve gastrectomy than after gastric bypass (HR 1.54, 95% CI 1.06-2.24). CONCLUSIONS: The overall survival following sleeve gastrectomy seems to compare well with gastric bypass and may even be better during recent years. A tailored surgical approach in relation to patients' diabetes status may optimize survival in patients selected for bariatric surgery (i.e., sleeve gastrectomy for patients without diabetes and gastric bypass for patients with diabetes).

Journal article

Chidambaram S, Maheswaran Y, Patel K, Sounderajah V, Hashimoto DA, Seastedt KP, McGregor AH, Markar SR, Darzi Aet al., 2022, Using Artificial Intelligence-Enhanced Sensing and Wearable Technology in Sports Medicine and Performance Optimisation, SENSORS, Vol: 22

Journal article

Kamarajah SK, Markar SR, Phillips AW, Kunene V, Fackrell D, Salti GI, Dahdaleh FS, Griffiths EAet al., 2022, Survival benefit of adjuvant chemotherapy following neoadjuvant therapy and oesophagectomy in oesophageal adenocarcinoma., Eur J Surg Oncol, Vol: 48, Pages: 1980-1987

BACKGROUND: The evidence assessing the additional benefits of adjuvant chemotherapy (AC) following neoadjuvant therapy (NAT; i.e. chemotherapy or chemoradiotherapy) and oesophagectomy for oesophageal adenocarcinoma (EAC) are limited. This study aimed to determine whether AC improves long-term survival in patients receiving NAT and oesophagectomy. METHODS: Patients receiving oesophagectomy for EAC following NAT from 2004 to 2016 were identified from the National Cancer Data Base (NCDB). To account for immortality bias, patients with survival ≤3 months were excluded to account for immortality bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of AC on overall survival. RESULTS: Overall, 12,972 (91%) did not receive AC and 1,255 (9%) received AC. After PSM there were 2,485 who did not receive AC and 1,254 who did. After matching, AC was associated with improved survival (median: 38.5 vs 32.3 months, p < 0.001), which remained after multivariable adjustment (HR: 0.78, CI95%: 0.71-0.87). On multivariable interaction analyses, this benefit persisted in subgroup analysis for nodal status: N0 (HR: 0.85, CI95%: 0.69-0.96), N1 (HR: 0.66, CI95%: 0.56-0.78), N2/3 (HR: 0.80, CI95%: 0.66-0.97) and margin status: R0 (HR: 0.77, CI95%: 0.69-0.86), R1 (HR: 0.60, CI95%: 0.43-0.85). Further, patients with stable disease following NAT (HR: 0.60, CI95%: 0.59-0.80) or downstaged (HR: 0.80, CI95%: 0.68-0.95) disease had significant survival benefit after AC, but not patients with upstaged disease. CONCLUSION: AC following NAT and oesophagectomy is associated with improved survival, even in node-negative and margin-negative disease. NAT response may be crucial in identifying patients who will benefit maximally from AC, and thus future research should be focused on identifying molecular phenotype of tumours that respond to chemotherapy to improve outcomes.

Journal article

Singh P, Gossage J, Markar S, Pucher PH, Wickham A, Weblin J, Chidambaram S, Bull A, Pickering O, Mythen M, Maynard N, Grocott M, Underwood Tet al., 2022, Association of Upper Gastrointestinal Surgery of Great Britain and Ireland (AUGIS)/Perioperative Quality Initiative (POQI) consensus statement on intraoperative and postoperative interventions to reduce pulmonary complications after oesophagectomy, BRITISH JOURNAL OF SURGERY, Vol: 109, Pages: 1096-1106, ISSN: 0007-1323

Journal article

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