The effect of a pre- and post- operative exercise program versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (The PERIOP-OG Trial): a randomized controlled trial.

INTRODUCTION: Although the benefits of post-operative rehabilitation in cancer surgery are well established, the role of prehabilitation is less defined. Oesophagogastric cancers present a unique opportunity to study the impact of prehabilitation during the neoadjuvant window, whether with chemotherapy or chemoradiotherapy (NCT) in patients who are frequently nutritionally depleted. This trial examines the impact of a community-based exercise program on patient fitness during and after the neoadjuvant window. METHODS: A pragmatic, randomized controlled multi-centre trial was undertaken in three centres. Inclusion criteria were patients aged ≥ 18 years planned for NCT and esophagectomy or gastrectomy. Participants were randomized 1:1 to an exercise prehabilitation group (EX) or to usual care (UC). The primary endpoint was cardiorespiratory fitness between baseline and pre-surgery timepoint using the 6-min walk test. Secondary endpoints included hand dynamometer, 10-sec sit to stand, activity behaviour, body mass index, semi-structured interviews, questionnaires assessing quality of life, surgical fear, general self-efficacy and mastery. RESULTS: Between March 2019 and December 2020, 71 participants were recruited: EX (n=36) or UC (n=35). From baseline to pre-surgery, the difference-in-difference for EX showed a significant improvement in 6MWT of 50.7m (P=0.05) compared to UC [mean (SD): 522.1m (+/-104.3) to 582.1m (+/-108) vs. 497.5m (+/-106.3) to 506.0 m (+/-140.4). There was no statistically significant DID for secondary outcome measures. CONCLUSIONS: This community exercise prehabilitation program significantly improves physical fitness for surgery, is feasible and provides a standardized framework for prescription of exercise in esophagogastric cancer patients undergoing NCT.

The effect of a pre- and post-operative exercise program versus standard care on physical activity and sedentary behavior of patients with esophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (the PERIOP-OG Trial): a randomized controlled trial†.

Neoadjuvant cancer treatment (NCT) reduces both physical fitness and physical activity (PA) levels, which can increase the risk of adverse outcomes in cancer patients. This study aims to determine the effect of exercise prehabilitation on PA and sedentary behavior (SB) in patients undergoing NCT and surgery for esophagogastric malignancies. This study is a randomized pragmatic controlled multi-center trial conducted across three Irish hospitals. Participants were aged ≥18 years scheduled for esophagectomy or gastrectomy and were planned for NCT and surgery. Participants were randomized to an exercise prehabilitation group (EX) that commenced following cancer diagnosis, continued to the point of surgery, and resumed following recovery from surgery for 6 weeks or to usual care (UC) who received routine treatment. The primary outcome measures were PA and SB. Between March 2019 and December 2020, 71 participants were recruited: EX (n = 36) or UC (n = 35). No significant differences were found between the EX group and UC group on levels of PA or SBs across all measured timepoints. Significant decreases in moderate-vigorous physical activity levels (MVPAs) were found between baseline and post-surgery (P = 0.028), pre-surgery and post-surgery (P = 0.001) and pre-surgery and 6-week follow-up (P = 0.022) for all participants. Step count also significantly decreased between pre-surgery and post-surgery (P < 0.001). Baseline aerobic fitness was positively associated to PA levels and negatively associated with SB. Esophagogastric cancer patients have lower than recommended levels of PA at the time of diagnosis and this decreased further following completion of NCT. An optional home- or group-based exercise intervention was not effective in improving PA levels or behaviors across the cancer treatment journey.

Evaluating analgesia strategies in patients who have undergone oesophagectomy-a systematic review and network meta-analysis of randomised clinical trials.

Optimal pain control following esophagectomy remains a topic of contention. The aim was to perform a systematic review and network meta-analysis (NMA) of randomized clinical trials (RCTs) evaluating the analgesia strategies post-esophagectomy. A NMA was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. Statistical analysis was performed using Shiny and R. Fourteen RCTs which included 565 patients and assessed nine analgesia techniques were included. Relative to systemic opioids, thoracic epidural analgesia (TEA) significantly reduced static pain scores at 24 hours post-operatively (mean difference (MD): -13.73, 95% Confidence Interval (CI): -27.01-0.45) (n = 424, 12 RCTs). Intrapleural analgesia (IPA) demonstrated the best efficacy for static (MD: -36.2, 95% CI: -61.44-10.96) (n = 569, 15 RCTs) and dynamic (MD: -42.90, 95% CI: -68.42-17.38) (n = 444, 11 RCTs) pain scores at 48 hours. TEA also significantly reduced static (MD: -13.05, 95% CI: -22.74-3.36) and dynamic (MD: -18.08, 95% CI: -31.70-4.40) pain scores at 48 hours post-operatively, as well as reducing opioid consumption at 24 hours (MD: -33.20, 95% CI: -60.57-5.83) and 48 hours (MD: -42.66, 95% CI: -59.45-25.88). Moreover, TEA significantly shortened intensive care unit (ICU) stays (MD: -5.00, 95% CI: -6.82-3.18) and time to extubation (MD: -4.40, 95% CI: -5.91-2.89) while increased post-operative forced vital capacity (MD: 9.89, 95% CI: 0.91-18.87) and forced expiratory volume (MD: 13.87, 95% CI: 0.87-26.87). TEA provides optimal pain control and improved post-operative respiratory function in patients post-esophagectomy, reducing ICU stays, one of the benchmarks of improved post-operative recovery. IPA demonstrates promising results for potential implementation in the future following esophagectomy.

Evaluating mesh fixation techniques for ventral hernia repair: A systematic review and network meta-analysis of randomised control trials.

INTRODUCTION: There is uncertainty regarding the optimal mesh fixation techniques for laparoscopic ventral and incisional hernia repair. AIM: To perform a systematic review and network meta-analysis of randomised control trials (RCTs) to investigate the advantages and disadvantages associated with absorbable tacks, non-absorbable tacks, non-absorbable sutures, non-absorbable staples, absorbable synthetic glue, absorbable sutures and non-absorbable tacks, and non-absorbable sutures and non-absorbable tacks. METHODS: A systematic review was performed as per PRISMA-NMA guidelines. Odds ratios (ORs) and mean differences (MDs) were extracted to compare the efficacy of the surgical approaches. RESULTS: Nine RCTs were included with 707 patients. Short-term pain was significantly reduced in non-absorbable staples (MD; -1.56, confidence interval (CI); -2.93 to -0.19) and non-absorbable sutures (MD; -1.00, CI; -1.60 to -0.40) relative to absorbable tacks. Recurrence, length of stay, operative time, conversion to open surgery, seroma and haematoma formation were unaffected by mesh fixation technique. CONCLUSION: Short-term post-operative pain maybe reduced by the use of non-absorbable sutures and non-absorbable staples. There is clinical equipoise between each modality in relation to recurrence, length of stay, and operative time.

Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: Optimal surgical management for gastric cancer remains controversial. We aimed to perform a network meta-analysis (NMA) of randomized clinical trials (RCTs) comparing outcomes after open gastrectomy (OG), laparoscopic-assisted gastrectomy (LAG), and robotic gastrectomy (RG) for gastric cancer. METHODS: A systematic search of electronic databases was undertaken. An NMA was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. Statistical analysis was performed using R and Shiny. RESULTS: Twenty-two RCTs including 6890 patients were included. Overall, 49.6% of patients underwent LAG (3420/6890), 46.6% underwent OG (3212/6890), and 3.7% underwent RG (258/6890). At NMA, there was a no significant difference in recurrence rates following LAG (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.77-1.49) compared with OG. Similarly, overall survival (OS) outcomes were identical following OG and LAG (OS: OG, 87.0% [1652/1898] vs. LAG: OG, 87.0% [1650/1896]), with no differences in OS in meta-analysis (OR 1.02, 95% CI 0.77-1.52). Importantly, patients undergoing LAG experienced reduced intraoperative blood loss, surgical incisions, distance from proximal margins, postoperative hospital stays, and morbidity post-resection. CONCLUSIONS: LAG was associated with non-inferior oncological and surgical outcomes compared with OG. Surgical outcomes following LAG and RG superseded OG, with similar outcomes observed for both LAG and RG. Given these findings, minimally invasive approaches should be considered for the resection of local gastric cancer, once surgeon and institutional expertise allows.

Successful maintenance of process and outcomes for oesophageal cancer surgery in Ireland during the first wave of the COVID-19 pandemic.

INTRODUCTION: The emergence of the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the coronavirus disease COVID-19 has impacted enormously on non-COVID-19-related hospital care. Curtailment of intensive care unit (ICU) access threatens complex surgery, particularly impacting on outcomes for time-sensitive cancer surgery. Oesophageal cancer surgery is a good example. This study explored the impact of the pandemic on process and short-term surgical outcomes, comparing the first wave of the pandemic from April to June in 2020 with the same period in 2019. METHODS: Data from all four Irish oesophageal cancer centres were reviewed. All patients undergoing resection for oesophageal malignancy from 1 April to 30 June inclusive in 2020 and 2019 were included. Patient, disease, and peri-operative outcomes (including COVID-19 infection) were compared. RESULTS: In 2020, 45 patients underwent oesophagectomy, and 53 in the equivalent period in 2019. There were no differences in patient demographics, co-morbidities, or use of neoadjuvant therapy. The median time to surgery from neoadjuvant therapy was 8 weeks in both 2020 and 2019. There were no significant differences in operative interventions between the two time periods. There was no difference in operative morbidity in 2020 and 2019 (28% vs 40%, p = 0.28). There was no in-hospital mortality in either period. No patient contracted COVID-19 in the perioperative period. CONCLUSIONS: Continuing surgical resection for oesophageal cancer was feasible and safe during the COVID-19 pandemic in Ireland. The national response to this threat was therefore successful by these criteria in the curative management of oesophageal cancer.

Surgery by a minimally invasive approach is associated with improved textbook outcomes in oesophageal and gastric cancer.

INTRODUCTION: Textbook outcome (TBO) is a composite measure of a number of peri-operative and clinical outcomes in oesophagogastric malignancy. It has previously been shown that TBOs are associated with improved overall survival in both oesophageal and gastric cancer. The influence of a minimally invasive approach (MIA) on TBO is not well defined. The purpose of this study is to validate TBO in our population, examine the influence of a MIA on achieving a TBO, and the impact of TBO on long-term survival. METHODS: 269 patients undergoing oesophagectomy and 258 patients undergoing subtotal or total gastrectomy were included in this study. Demographic, clinical and pathological differences between patients with and without a TBO were compared using univariable and multivariable analysis. Overall survival for those with and without a TBO was examined. The influence of MIA on overall survival and TBO was determined using Cox proportional hazard models. RESULTS: Patients undergoing oesophagectomy and gastrectomy were significantly more likely to achieve a TBO when MIA was used (p = 0.01 and 0.001 respectively). When MIA is included as an outcome measure patients achieving a TBO show improved overall survival in both oesophageal and gastric cancer. MIA, clear resection margins and no unplanned admission to critical care are the strongest predictors of overall survival from the putative bundle of TBO parameters. CONCLUSION: Minimally invasive surgery is associated with improved TBO. Completion of a minimally invasive approach should be considered for inclusion as a textbook parameter.

Options in Bariatric Surgery: Modeled Decision Analysis Supports One-Anastomosis Gastric Bypass as the Treatment of Choice when Type 2 Diabetes Is Present.

BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) represent significant healthcare burdens. Surgical management is superior to traditional medical therapy. Laparoscopic sleeve gastrectomy (LSG) and gastric bypass (both Roux-en-Y (RYGB) and one anastomosis gastric bypass (OAGB) are the most commonly performed metabolic procedures. It remains unclear which gives the optimal quality-of-life pay-off in the context of T2DM. This study compares LSG, RYGB, and OAGB in the management of T2DM and obesity using modeled decision analysis. Alternative approaches were assessed considering efficacy of interventions, post-operative complications, and quality of life outcomes to determine the optimal approach. METHODS: Modeled decision analysis was performed from the patent's perspective comparing best medical management (MM), SG, RYGB, OAGB, and LAGB. The base case is a 40-year-old female with a body mass index (BMI) of 40 and T2DM. Input variables were calculated based on published decision analyses and a literature review. Utilities were based on previous studies. Sensitivity analysis was performed. The payoff was quality-adjusted life years (QALYs) 5 years from intervention. TreeAge Pro modeling software was used for analysis. RESULTS: In 5-years post-procedure, OAGB gave the optimal QALY payoff of 3.65 QALYs (reviewer 2). RYGB gave 3.47, SG gave 3.08, LAGB gave 2.62 and MM 2.45 QALYs. Three input variables proved sensitive. RYGB is optimal if its metabolic improvement rates exceed 86%. It is also optimal if metabolic improvement rates in OAGB drop below 71.8% or if the utility of OAGB drops below 0.759. CONCLUSION: OAGB gives the optimal QALY payoff in treatment of T2DM. RYGB and SG also improve metabolic outcomes and remain viable options in selected patients.

The effect of a pre- and post-operative exercise programme versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (The PERIOP-OG Trial): Study protocol for a randomised controlled trial.

BACKGROUND: Advances in peri-operative oncological treatment, surgery and peri-operative care have improved survival for patients with oesophagogastric cancers. Neoadjuvant cancer treatment (NCT) reduces physical fitness, which may reduce both compliance and tolerance of NCT as well as compromising post-operative outcomes. This is particularly detrimental in a patient group where malnutrition is common and surgery is demanding. The aim of this trial is to assess the effect on physical fitness and clinical outcomes of a comprehensive exercise training programme in patients undergoing NCT and surgical resection for oesophagogastric malignancies. METHODS: The PERIOP-OG trial is a pragmatic, multi-centre, randomised controlled trial comparing a peri-operative exercise programme with standard care in patients with oesophagogastric cancers treated with NCT and surgery. The intervention group undergo a formal exercise training programme and the usual care group receive standard clinical care (no formal exercise advice). The training programme is initiated at cancer diagnosis, continued during NCT, between NCT and surgery, and resumes after surgery. All participants undergo assessments at baseline, post-NCT, pre-surgery and at 4 and 10 weeks after surgery. The primary endpoint is cardiorespiratory fitness measured by demonstration of a 15% difference in the 6-min walk test assessed at the pre-surgery timepoint. Secondary endpoints include measures of physical health (upper and lower body strength tests), body mass index, frailty, activity behaviour, psychological and health-related quality of life outcomes. Exploratory endpoints include a health economics analysis, assessment of clinical health by post-operative morbidity scores, hospital length of stay, nutritional status, immune and inflammatory markers, and response to NCT. Rates of NCT toxicity, tolerance and compliance will also be assessed. DISCUSSION: The PERIOP-OG trial will determine whether, when compared to usual care, exercise training initiated at diagnosis and continued during NCT, between NCT and surgery and then during recovery, can maintain or improve cardiorespiratory fitness and other physical, psychological and clinical health outcomes. This trial will inform both the prescription of exercise regimes as well as the design of a larger prehabilitation and rehabilitation trial to investigate whether exercise in combination with nutritional and psychological interventions elicit greater benefits. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03807518 . Registered on 1 January 2019.

Perioperative prehabilitation and rehabilitation in esophagogastric malignancies: a systematic review.

Cancers of the esophagus and stomach are challenging to treat. With the advent of neoadjuvant therapies, patients frequently have a preoperative window with potential to optimize their status before major resectional surgery. It is unclear as to whether a prehabilitation or optimization program can affect surgical outcomes. This systematic review appraises the current evidence for prehabilitation and rehabilitation in esophagogastric malignancy. A literature search was performed according to PRISMA guidelines using PubMed, EMBASE, Cochrane Library, Google Scholar, and Scopus. Studies including patients undergoing esophagectomy or gastrectomy were included. Studies reporting on at least one of aerobic capacity, muscle strength, quality of life, morbidity, and mortality were included. Twelve studies were identified for inclusion, comprising a total of 937 patients. There was significant heterogeneity between studies, with a variety of interventions, timelines, and outcome measures reported. Inspiratory muscle training (IMT) consistently showed improvements in functional status preoperatively, with three studies showing improvements in respiratory complications with IMT. Postoperative rehabilitation was associated with improved clinical outcomes. There may be a role for prehabilitation among patients undergoing major resectional surgery in esophagogastric malignancy. A large randomized controlled trial is warranted to investigate this further.

Options in bariatric surgery: modeled decision analysis supports Roux-en-Y gastric bypass and sleeve gastrectomy as the treatments of choice.

BACKGROUND: Obesity is a chronic disease associated with significant morbidity and mortality. Bariatric surgery has been shown to significantly reduce both morbidity and mortality. Numerous surgical strategies exist, but the most frequently used worldwide are adjustable gastric banding, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB). It is not clear which of these strategies provides the optimal quality-of-life pay-off. OBJECTIVE: Modeled decision analysis allows comparison of different treatment interventions allowing for plausible differences in input variables. This facilitates establishment of the optimal intervention under numerous conditions. SETTING: University Hospital, Ireland. METHODS: Modeled decision analysis was performed from the patient's perspective comparing best medical therapy, adjustable gastric banding, SG, and RYGB. Input variables were calculated based on previously published decision analyses and a systematic search of obesity-related literature. Utilities were based on previously published studies. One-way sensitivity analysis was performed. Sensitive variables underwent 3-way analysis. RESULTS: The optimal treatment strategy in the base case was RYGB with a quality-adjusted life-year payoff (QALY) of 1.53 QALYs at 2 years postprocedure. Sleeve gastrectomy provided 1.49 QALYs. Medical therapy and adjustable gastric banding provided .98 and .96 QALYs, respectively. Rate of complications in RYGB and the utility of SG and RYGB proved sensitive. If complication rates are high, SG becomes the optimal strategy. Sensitive thresholds were established for the utility of SG and RYGB at .804 and .78, respectively. CONCLUSION: SG and RYGB offer similar outcomes in terms of QALY payoffs. Decision making should be in line with institutional and patient preference.

A study evaluating cost awareness amongst surgeons in a health service under financial strain.

BACKGROUND: Despite having considerable influence over resource allocation clinicians possess poor knowledge of healthcare costs. This study evaluated surgeons' cost-awareness with regard to surgical equipment and assessed attitudes towards health economics training using survey format. MATERIALS AND METHODS: An online survey was distributed to 326 surgeons across a range of specialties in Ireland. Respondents were asked about their surgical expertise, previous training in health economics, and its role in the surgical curriculum. They were also asked to estimate the recommended retail price (RRP) of 17 commonly used items of surgical equipment. Answers within ±25% of the RRP were considered correct. RESULTS: Of 140 respondents, 62 (44.3%) were on a surgical training scheme and 16 (11.4%) were consultants. Overall, surgeons correctly estimated the RRP of only 14.0% of items. There was no difference in accuracy between surgeons in later years of training compared to their junior counterparts (13.1 ±â€¯8.8% versus 15.0 ±â€¯8.8%, p = 0.115). The highest individual score was six out of 17 items correctly estimated. Participants overestimated the cost of low-cost items by 347.7% and underestimated the cost of high-cost items by 35.5%. Only 5.7% of participants had received undergraduate training in health economics but 75.0% felt it should be included in the curriculum. Over two-thirds said their practice would change if they had better knowledge of the cost of surgical equipment. CONCLUSION: The majority of surgeons receive little training in health economics and have poor knowledge of the cost of surgical equipment. Most would welcome more training at both an undergraduate and postgraduate level. An opportunity exists to promote cost awareness in the operating room, which could lead to a reduction in waste and improved use of resources.

Meta-Analysis of Enhanced Recovery Protocols in Bariatric Surgery.

BACKGROUND: Enhanced recovery after surgery (ERAS) guidelines, fast-track protocols, and alternative clinical pathways have been widely promoted in a variety of disciplines leading to improved outcomes in post-operative morbidity and length of stay (LOS). This meta-analysis assesses the implications of standardized management protocols in bariatric surgery. METHODS: The PRISMA guidelines were adhered to. Databases were searched with the application of pre-defined inclusion and exclusion criteria. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Individual protocols and surgical approaches were assessed through subgroup analysis, and sensitivity analysis of methodological quality was performed. RESULTS: A total of 1536 studies were screened; 13 studies were eventually included for meta-analysis involving a total of 6172 patients. Standardized perioperative techniques were associated with a savings of 19.5 min in operative time (p < 0.01), as well as a LOS which was shortened by 1.5 days (p < 0.01). Pooled post-operative morbidity rates also favored enhanced recovery care protocols (OR 0.7%, 95% CI 0.6-0.9%, p < 0.01). CONCLUSION: Bariatric surgery involves a complex cohort of patients who require high-quality evidence-based care to improve outcomes. Consensus guidelines on the feasibility of ERAS and alternative clinical pathways are required in the setting of bariatric surgery.

Meta-analysis of outcomes of endoscopic ultrasound-guided gallbladder drainage versus percutaneous cholecystostomy for the management of acute cholecystitis.

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage is a novel method of treating acute cholecystitis in patients deemed too high risk for surgery. It involves endoscopic stent placement between the gallbladder and the alimentary tract to internally drain the infection and is an alternative to percutaneous cholecystostomy (PC). This meta-analysis assesses the clinical outcomes of high-risk patients undergoing endoscopic drainage with an acute cholecystoenterostomy (ACE) compared with PC in acute cholecystitis. METHODS: A literature search was performed using the preferred reporting items for systematic reviews and meta-analyses guidelines. Databases were searched for studies reporting outcomes of patients undergoing ACE or PC. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: A total of 1593 citations were reviewed; five studies comprising 495 patients were ultimately selected for analysis. There were no differences in technical or clinical success rates between the two groups on pooled meta-analysis. ACE had significantly lower post-procedural pain scores (mean difference - 3.0, 95% CI - 2.3 to - 3.6, p < 0.001, on a 10-point pain scale). There were no statistically significant differences in procedure complications between groups. Re-intervention rates were significantly higher in the PC group (OR 4.3, 95% CI 2.0-9.3, p < 0.001). CONCLUSION: ACE is a promising alternative to PC in high-risk patients with acute cholecystitis, with equivalent success rates, improved pain scores and lower re-intervention rates, without the morbidities associated with external drainage.

Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

BACKGROUND: Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. METHODS/DESIGN: PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. DISCUSSION: This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. TRIAL REGISTRATION: NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).