The Prognostic Impact of Minimally Invasive Esophagectomy on Survival after Esophagectomy following a Delayed Interval after Chemoradiotherapy; A Secondary Analysis of the DICE Study.

OBJECTIVE: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT). BACKGROUND: Previously, we established that a prolonged interval after CRT prior to esophagectomy was associated with poorer long-term survival. METHODS: This was an international multi-center cohort study involving seventeen tertiary centers, including patients who received CRT followed by surgery between 2010-2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approach. RESULTS: 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and two years after CRT. Significant differences were observed in ASA grade, radiation dose, clinical T stage, and histological subtype. There were no significant differences between the groups in age, sex, BMI, pathological T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate (P=0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI 1.14 to 2.5) and propensity matched analysis (P=0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE, in 40-50Gy dose groups (HR=1.9; 95% CI 1.2 to 3.0), and in patients having surgery within six months of CRT (HR=1.6; 95% CI 1.1 to 2.2). CONCLUSION: MIE was associated with an improved overall survival compared to OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett's oesophagus and stage I oesophageal adenocarcinoma.

Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment.

Long-term survival is not affected by severity of complications following esophagectomy.

INTRODUCTION: Outcomes following esophagectomy for esophageal cancer have continued to improve over the last 30 years. Post-operative complications impact upon peri-operative and short-term survival but the effect on long-term survival remains debated. This study aims to investigate the effect of post-operative complications on long-term survival following esophagectomy. MATERIALS AND METHODS: All patients who underwent an esophagectomy between January 2010 and January 2019 were included from a single high-volume center. Data was collected contemporaneously. Patients were separated into three groups; those who experienced no, or very minor complications (Clavien-Dindo 0 or 1), minor complications (Clavien-Dindo 2), and major complications (Clavien-Dindo 3-4), at 30 days. To correct for short-term mortality effects, those who died during the index hospital admission were excluded. Overall survival was analyzed using Kaplan-Meier and log rank testing. RESULTS: The study cohort comprised 721 patients. There were 42.4% (306/721), 29.5% (213/721) and 25.7% (185/721) in the Clavien-Dindo 0-1, Clavien-Dindo 2, and Clavien-Dindo 3-4 group respectively. Seventeen patients (2.4%) died during their index hospital admission and were therefore excluded. There was no significant difference between median survival across the 3 groups (50, 57 and 52 months). Across all 3 groups, overall long-term survival rates were equivalent at 1 (87.5%, 84.9%, 83.2%), 3 (59.7%, 59.6%, 54.2%), and 5 years (43.9%, 48.9%, 45.7%) (p = 0.806). The only factors independently associated with survival in this cohort, were male gender, Charlson comorbidity index, and overall pathological stage of disease. CONCLUSION: Long-term survival is not affected by peri-operative complications, irrespective of severity, following esophagectomy. Further study into the long-term quality of life is required.

Structural basis of human U5 snRNP late biogenesis and recycling.

Pre-mRNA splicing by the spliceosome requires the biogenesis and recycling of its small nuclear ribonucleoprotein (snRNP) complexes, which are consumed in each round of splicing. The human U5 snRNP is the ~1 MDa 'heart' of the spliceosome and is recycled through an unknown mechanism involving major architectural rearrangements and the dedicated chaperones CD2BP2 and TSSC4. Late steps in U5 snRNP biogenesis similarly involve these chaperones. Here we report cryo-electron microscopy structures of four human U5 snRNP-CD2BP2-TSSC4 complexes, revealing how a series of molecular events primes the U5 snRNP to generate the ~2 MDa U4/U6.U5 tri-snRNP, the largest building block of the spliceosome.

Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study.

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.

Prognostic implications of the extent of downstaging after neoadjuvant therapy for oesophageal adenocarcinoma and oesophageal squamous cell carcinoma.

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 neoadjuvant therapy remains controversial. Identifying biomarkers associated with response to neoadjuvant regimens may permit individualized treatment.

Histological prognosticators in neoadjuvant naive oesophageal cancer patients.

PURPOSE: Prognosis of oesophageal cancer is primarily based upon the TNM stage of the disease. However, even in those with similar TNM staging, survival can be varied. Additional histopathological factors including venous invasion (VI), lymphatic invasion (LI) and perineural invasion (PNI) have been identified as prognostic markers yet are not part of TNM classification. The aim of this study is to determine the prognostic importance of these factors and overall survival in patients with oesophageal or junctional cancer who underwent transthoracic oesophagectomy as the unimodality treatment. METHODS: Data from patients who underwent transthoracic oesophagectomy for adenocarcinoma without neoadjuvant treatment were reviewed. Patients were treated with radical resection, with a curative intent using a transthoracic Ivor Lewis or three staged McKeown approach. RESULTS: A total of 172 patients were included. Survival was poorer when VI, LI and PNI were present (p<0.001), with the estimated survival being significantly worse (p<0.001) when patients were stratified according to the number of factors present. Univariable analysis of factors revealed VI, LI and PNI were all associated with survival. Presence of LI was independently predictive of incorrect staging/upstaging in multivariable logistic regression analysis (OR 12.9 95% CI 3.6-46.6, p<0.001). CONCLUSION: Histological factors of VI, LI and PNI are markers of aggressive disease and may have a role in prognostication and decision-making prior to treatment. The presence of LI as an independent marker of upstaging could be a potential indication for the use of neoadjuvant treatment in patients with early clinical disease.

Multicenter, Prospective Cohort Study of Oesophageal Injuries and Related Clinical Outcomes (MUSOIC study).

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.

The Surgical Trainer.

The 'no training today, no surgeons tomorrow' campaign on social media has been a rallying call for all surgeons worldwide to prioritize training as part of the COVID-19 pandemic recovery process. The campaign calls for all trainers to treat every case as a training opportunity. However, this raises some important questions. Who are the surgical trainers responsible for these changes? Are modern surgical trainers defined by a role within their department? How can such contributions to training be recognized? These questions are discussed within this perspectives article, including the need for the professionalization of the trainer role and how contributions to training can be formalized and supported within departments and at a national or international level.

Are intra-operative gastric drainage procedures necessary in esophagectomy: a systematic review and meta-analysis.

PURPOSE: Surgical pyloroplasty or pyloromyotomy are often performed during esophagectomy with a view of improving gastric conduit drainage. However, the clinical importance of this is not clear, and some centers opt to omit this step. The aim of this meta-analysis is to compare the rates of pulmonary complications, anastomotic leak, mortality, delayed gastric emptying, and the need for further pyloric intervention, in patients undergoing esophagectomy with and without a drainage procedure. METHODS: A database search of Medline, EMBASE, and Cochrane Library was performed to identify randomized control trials and cohort studies published between 2000 and 2020 which compared outcomes of esophagectomy with and without drainage procedures. A random-effects meta-analysis model was used to compare the rates of pulmonary complications, anastomotic leak, mortality, delayed gastric emptying, and the need for further pyloric intervention. RESULTS: Three randomized and 12 non-randomized publications were identified, comprising a total of 2339 patients. No significant differences were found between the two groups with regard to pulmonary complications (RR 1.02 [95% CI, 0.78-1.33], p = 0.91), anastomotic leak (RR 1.14 [95% CI, 0.80-1.62], p = 0.48), mortality (RR 0.53 [95% CI, 0.23-1.26], p = 0.15), delayed gastric emptying (RR 0.98 [95% CI, 0.59-1.62], p = 0.93), and the need for further pyloric intervention (RR 1.99 [95% CI, 0.56-7.08], p = 0.29). CONCLUSION: Where post-operative pyloric treatment is available on demand, surgical pyloric drainage procedures may not have any significant clinical impact on patient outcomes for patients undergoing esophagectomy, though further good-quality randomized controlled trials are needed to confirm this.

Exploring factors influencing uptake and adherence to a home-based prehabilitation physical activity and exercise intervention for patients undergoing chemotherapy before major surgery (ChemoFit): a qualitative study.

OBJECTIVES: Preoperative exercise training can improve cardiorespiratory fitness before major surgery. However, little is known about what influences participation and adherence in high-risk patient groups. We identified barriers and facilitators to uptake, engagement and adherence to a presurgical, home-based physical activity and exercise intervention called ChemoFit delivered during chemotherapy and before major oesophagogastric surgery. DESIGN: A qualitative study using focus group discussions and individual semi-structured interviews was conducted. All were audio-recorded, transcribed verbatim and data thematically analysed. SETTING: Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Hospitals Foundation Trust. PARTICIPANTS: Patients with oesophagogastric cancer who participated in the ChemoFit intervention recruited between March 2020 and January 2021. INTERVENTION: A home-based physical activity and exercise intervention involving cardiovasular and strength exercise using resistance bands and pedometers to monitor step count. Weekly telephone calls provided feedback, support and positive reinforcement. RESULTS: Twenty-two participants (18 men, 4 women; aged 67±8 years old) took part in a focus group discussion (n=17) or a semi-structured interview (n=5). Fifteen themes were identified from the data generated. Participants reported that the intervention was physically and mentally beneficial, and data highlighted features of the intervention that influenced uptake and adherence. An opportunity to increase the likelihood of surviving the pending operation was reported by participants as the most salient factor to engagement, and using the intervention as a distraction from illness and taking steps to positively influence the situation were the most salient factors to adherence. CONCLUSIONS: Uptake to the ChemoFit intervention was encouraged by provision of information that participation could reduce surgical risk and that participants could play an active role in risk reduction. Adherence was facilitated by the intervention being considered a positive distraction and participants being able to do something that could ultimately provide benefit. While participants reported difficulties and avoidance with some of the exercises recommended, understanding the importance of physical activity and exercise as part of their treatment regimen led to individual adaptations to intervention components to reach individual goals. TRIAL REGISTRATION NUMBER: NCT04194463.

A feasibility trial of prehabilitation before oesophagogastric cancer surgery using a multi-component home-based exercise programme: the ChemoFit study.

BACKGROUND: Treatment for locally advanced oesophagogastric adenocarcinoma involves neoadjuvant chemotherapy which has a negative impact on patient fitness. Using 'prehabilitation' to increase activity levels and fitness may affect physiology, postoperative outcomes and improve patient wellbeing and quality of life. The aims of the trial were to address the feasibility and acceptability of recruiting participants to a home-based prehabilitation programme and provide data to allow design of future studies. METHODS: We recruited patients to a single-arm feasibility trial of home-based exercise prehabilitation. Eligible patients were aged ≥18years, had operable oesophageal or gastric adenocarcinoma and were receiving neoadjuvant chemotherapy at our tertiary referral hospital. All participants commenced a home-based exercise programme utilising pedometers and step counting to target daily aerobic exercise sessions alongside daily strengthening exercises. A weekly telephone consultation directed the exercise programme and facilitated weekly data collection. The primary (feasibility) outcomes for the trial were (a) recruitment rate, (b) completion rate, (c) engagement with the programme (use of pedometers, recording step counts, telephone consultations) and (d) compliance with exercise sessions, exercise intensity and strengthening exercises. RESULTS: There were 42 patients recruited, and the recruitment rate was 72.4% (42/58). 92.3% (36/39) of patients completed the exercise programme. There was 98.7% (IQR 93.2-100.0%) compliance with wearing a pedometer and recording data, and 100.0% (IQR 93.1-100.0%) compliance with a weekly telephone consultation. Exercise sessions and strengthening exercises were completed 70.2% (IQR 53.1-88.9%) and 69.4% (IQR 52.1-84.3%) of the time, respectively. Appropriate exercise intensity was recorded 96% (IQR 85.4-99.4%) of the time. There were no adverse events. Participants were enrolled in the exercise programme for a median of 91 days (IQR 84 to 105 days). CONCLUSIONS: The results of this trial support the feasibility and acceptability of recruiting participants to an appropriately powered randomised controlled trial of prehabilitation. TRIAL REGISTRATION: Clinicaltrials.gov NCT04194463 . Registered on 11th December 2019-retrospectively registered.

Survival benefit of adjuvant chemotherapy following neoadjuvant therapy and oesophagectomy in oesophageal adenocarcinoma.

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.

Incidence, Diagnosis and Management of Malabsorption Following Oesophagectomy: a Systematic Review.

BACKGROUND: Survival following oesophagectomy for cancer is improving, resulting in increased focus on quality of life and survivorship. Malabsorption syndrome is multifactorial and includes exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO) and bile acid malabsorption (BAM). The aim of this study was to evaluate the reported incidence and management of malabsorption syndromes post-oesophagectomy. METHODS: A systematic search of PubMed, EMBASE, MEDLINE, Scopus and the Cochrane Library evaluating incidence, diagnosis and management of malabsorption was performed for studies published until December 2021. RESULTS: Of 464 identified studies, eight studies (n = 7 non-randomised longitudinal studies) were included where patients were identified with malnutrition following oesophagectomy. Studies included a combined sample of 328 (range 7-63) patients. Malabsorption syndromes including EPI, SIBO and BAM occurred in 15.9-100%, 37.8-100% and 3.33-100% over 21 days-60 months, 1-24 months and 1-24 months respectively. There was no consensus definition for EPI, SIBO or BAM, and there was variation in diagnostic methods. Diagnostic criteria varied from clinical (gastrointestinal symptoms or weight loss), or biochemical (faecal elastase, hydrogen breath test and Selenium-75-labelled synthetic bile acid measurements). Treatment modalities using pancreatic enzyme replacement, rifaximin or colesevelam showed improvement in symptoms and weight in all studies, where investigated. CONCLUSIONS: Malabsorption syndromes following oesophagectomy are under-recognised, and thus under-reported. The resultant gastrointestinal symptoms may have a negative effect on post-operative quality of life. Current literature suggests benefit with outlined therapies; however, greater understanding of these conditions, their diagnosis and management is required to further understand which patients will benefit from treatment.

Significance of neoadjuvant downstaging in gastric adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy is established in the treatment of gastric adenocarcinoma. Histopathological regression may have important prognostic implications. There are little data comparing clinical outcomes of patients with gastric adenocarcinoma that received neoadjuvant treatment and those neoadjuvant naive. The aim of this study is to determine the impact of neoadjuvant chemotherapy upon prognosis of patients being treated for gastric adenocarcinoma. METHODS: Consecutive patients with gastric cancer from a single center between 2007 and 2017 were evaluated. Patients were treated with either a subtotal or total gastrectomy with D2 lymphadenectomy. Stage-by-stage comparison of the extent of pathological downstaging was conducted for patients who received neoadjuvant treatment (ypTNM) and those who did not (pTNM) using the TNM eighth edition. RESULTS: Overall, 384 patients underwent gastrectomy, 141 patients received neoadjuvant chemotherapy, and 86 patients (58.1%) were downstaged. Downstaged patients had improved overall survival compared to patients who did not respond to neoadjuvant chemotherapy (not reported vs 66 months, P < .001). Downstaging by >3 stages was the strongest independent predictor of overall survival (hazard ratio: 0.17; 95% confidence interval 0.062-0.44). Overall survival was significantly better among patients in the ypTNM groups when a stage-by-stage comparison was performed with the pTNM group. CONCLUSION: Pathological stage is a more accurate predictor of prognosis compared clinical stage with downstaged patients benefiting from lower recurrence rates and improved overall survival. Patients downstaged due to neoadjuvant chemotherapy may potentially have more favorable clinical outcomes compared to stage-matched patients who did not receive this.

Is Local Endoscopic Resection a Viable Therapeutic Option for Early Clinical Stage T1a and T1b Esophageal Adenocarcinoma?: A Propensity-matched Analysis.

OBJECTIVE: The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus esophagectomy in node-negative cT1a and cT1b esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: The role of ER in the management of subsets of clinical T1N0 esophageal adenocarcinoma is controversial. METHODS: Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2545) and T1bN0 (n = 1281) esophageal adenocarcinoma that received either ER (cT1a, n = 1581; cT1b, n = 335) or esophagectomy (cT1a, n = 964; cT1b, n = 946). Propensity score matching and Cox analyses were used to account for treatment selection bias. RESULTS: ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b esophageal adenocarcinoma were 4% and 15%, respectively. In the matched cohort for cT1a cancers, ER had similar survival to esophagectomy [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.70-1.04, P = 0.1]. The corresponding 5-year survival for ER and esophagectomy were 70% and 74% (P = 0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66-1.14, P = 0.3). The corresponding 5-year survival for ER and esophagectomy were 53% versus 61% (P = 0.3), respectively. CONCLUSIONS: This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 esophageal adenocarcinoma. However, 15% of patients with cT1b esophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from esophagectomy with lymphadenectomy.

Definitive Chemoradiotherapy Compared to Neoadjuvant Chemoradiotherapy With Esophagectomy for Locoregional Esophageal Cancer: National Population-based Cohort Study.

AIM: Ongoing randomized controlled trials seek to evaluate the potential organ-preservation strategy of definitive chemoradiotherapy as a primary treatment for esophageal cancer. This population-based cohort study aimed to assess survival following definitive chemoradiotherapy (DCR) with or without salvage esophagectomy (SALV) in the treatment of esophageal cancer. PATIENTS AND METHODS: Data from the National Cancer Database (NCDB) from 2004 to 2015, was used to identify patients with nonmetastatic esophageal cancer receiving either DCR (n = 5977) or neoadjuvant chemoradiotherapy with planned esophagectomy (NCRS) (n = 13,555). Propensity score matching and multivariable analyses were used to account for treatment selection bias. Subset analyses compared patients receiving SALV after DCR with NCRS. RESULTS: Comparison of baseline demographics of the unmatched cohort revealed that patients receiving NCRS were younger, had a lower burden of medical comorbidities, lower proportion of squamous cell carcinoma (SCC), and more positive lymph nodes. Following matching, NCRS was associated with significantly improved survival compared with DCR [hazard ratio (HR): 0.60, 95% confidence Interval (CI): 0.57-0.63, P < 0.001], which persisted in subset analyses of patients with adenocarcinoma (HR: 0.60, 95% CI: 0.56-0.63, P < 0.001) and SCC (HR: 0.58, 95% CI: 0.53-0.63, P < 0.001). Of 829 receiving SALV after DCR, 823 patients were matched to 1643 NCRS. There was no difference in overall survival between SALV and NCRS (HR: 1.00, 95% CI: 0.90-1.11, P = 1.0). CONCLUSIONS: Surgery remains an integral component of the management of patients with esophageal cancer. Neoadjuvant therapy followed by planned esophagectomy appears to remain the optimum curative treatment regime in patients with locoregional esophageal cancer.