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.

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.

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.

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.

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.

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.

Acute Kidney Injury After Esophageal Cancer Surgery: Incidence, Risk Factors, and Impact on Oncologic Outcomes.

OBJECTIVE: To determine the incidence, risk factors, and consequences of AKI in patients undergoing surgery for esophageal cancer. SUMMARY OF BACKGROUND DATA: Esophageal cancer surgery is an exemplar of major operative trauma, with well-defined risks of respiratory, cardiac, anastomotic, and septic complications. However, there is a paucity of literature regarding AKI. METHODS: consecutive patients undergoing curative-intent surgery for esophageal cancer from 2011 to 2017 in 3 high-volume centers were studied. AKI was defined according to the AKI Network criteria. AKI occurred if, within 48 hours postoperatively, serum creatinine rose by 50% or by 0.3 mg/dL (26.5 µmol/L) from preoperative baseline. Complications were recorded prospectively. Multivariable logistic regression determined factors independently predictive of AKI. RESULTS: A total of 1135 patients (24.7%:75.3% female:male, with a mean age of 64, a baseline BMI of 27 kg m-2, and dyslipidemia in 10.2%), underwent esophageal cancer surgery, 85% having an open thoracotomy. Overall in-hospital mortality was 2.1%. Postoperative AKI was observed in 208 (18.3%) patients, with AKI Network 1, 2, and 3 in 173 (15.2%), 28 (2.5%), and 7 (0.6%), respectively. Of these, 70.3% experienced improved renal function within 48 hours. Preoperative factors independently predictive of AKI were age [P = 0.027, odds ratio (OR) 1.02 (1.00-1.04)], male sex [P = 0.015, OR 1.77 (1.10-2.81)], BMI at diagnosis [P < 0.001, OR 1.10 (1.07-1.14)], and dyslipidemia [P = 0.002, OR 2.14 (1.34-3.44)]. Postoperatively, AKI was associated with atrial fibrillation (P = 0.013) and pneumonia (P = 0.005). Postoperative AKI did not impact survival outcomes. CONCLUSION: AKI is common but mostly self-limiting after esophageal cancer surgery. It is associated with age, male sex, increased BMI, dyslipidemia, and postoperative morbidity.

Robotic Techniques in Esophagogastric Cancer Surgery: An Assessment of Short- and Long-Term Clinical Outcomes.

BACKGROUND: Robotic esophagogastric cancer surgery is gaining widespread adoption. This population-based cohort study aimed to compare rates of textbook outcomes (TOs) and survival from robotic minimally invasive techniques for esophagogastric cancer. METHODS: Data from the United States National Cancer Database (NCDB) (2010-2017) were used to identify patients with non-metastatic esophageal or gastric cancer receiving open surgery (to the esophagus, n = 11,442; stomach, n = 22,183), laparoscopic surgery (to the esophagus [LAMIE], n = 4827; stomach [LAMIG], n = 6359), or robotic surgery (to the esophagus [RAMIE], n = 1657; stomach [RAMIG], n = 1718). The study defined TOs as 15 or more lymph nodes examined, margin-negative resections, hospital stay less than 21 days, no 30-day readmissions, and no 90-day mortalities. Multivariable logistic regression and Cox analyses were used to account for treatment selection bias. RESULTS: Patients receiving robotic surgery were more commonly treated in high-volume academic centers with advanced clinical T and N stage disease. From 2010 to 2017, TO rates increased for esophageal and gastric cancer treated via all surgical techniques. Compared with open surgery, significantly higher TO rates were associated with RAMIE (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.27-1.58) and RAMIG (OR 1.30; 95% CI 1.17-1.45). For esophagectomy, long-term survival was associated with both TO (hazard ratio [HR 0.64, 95% CI 0.60-0.67) and RAMIE (HR 0.92; 95% CI 0.84-1.00). For gastrectomy, long-term survival was associated with TO (HR 0.58; 95% CI 0.56-0.60) and both LAMIG (HR 0.89; 95% CI 0.85-0.94) and RAMIG (HR 0.88; 95% CI 0.81-0.96). Subset analysis in high-volume centers confirmed similar findings. CONCLUSION: Despite potentially adverse learning curve effects and more advanced tumor stages captured during the study period, both RAMIE and RAMIG performed in mostly high-volume centers were associated with improved TO and long-term survival. Therefore, consideration for wider adoption but a well-designed phase 3 randomized controlled trial (RCT) is required for a full evaluation of the benefits conferred by robotic techniques for esophageal and gastric cancers.

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.

FLOT-regimen Chemotherapy and Transthoracic en bloc Resection for Esophageal and Junctional Adenocarcinoma.

BACKGROUND AND AIMS: The FLOT4-AIO trial established the FLOT regimen as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on FLOT with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, and oncologic outcomes. STUDY DESIGN: An observational cohort study on consecutive patients at 3 tertiary centers undergoing FLOT and TTE. Toxicity, operative complications (per ECCG definitions), tumor regression grade (TRG), recurrences and survival were documented, as well as pre and post FLOT assessment of sarcopenia and pulmonary physiology. RESULTS: 175 patients (cT2-4a, Nany) commenced treatment, 84% male, median age 65, 94% cT3/T4a, 73% cN+. 89% completed 4 preoperative cycles, and 35% all cycles. Grade 3/4 toxicities included neutropenia (12%), diarrhoea (13%), and infection (15%). Sarcopenia increased from 18% to 37% (P = 0.020), and diffusion capacity (DLCO) decreased by 8% (-34% + 25%; P < 0.010). On pathology, ypT3/4 was 59%, and ypN+54%, with 10% TRG 1, 14% TRG 2, and 76% TRG3-5, and R0 95%. 161 underwent TTE, with an in-hospital mortality of 0.6%, 24%-pneumonia, 11%-anastomotic leak, and Clavien Dindo ≥III in 27%. At a median follow up of 12 months (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%. CONCLUSION: FLOT and en bloc TTE was safe, with no discernible impact on operative complications, with 24% having a major pathologic response. Caveats include a limited pathologic response in the majority, and negative impact on muscle mass and lung physiology, and low use of adjuvant cycles. These data may provide a real-world benchmark for this complex care pathway.

Local Endoscopic Resection is Inferior to Gastrectomy for Early Clinical Stage T1a and T1b Gastric Adenocarcinoma: A Propensity-Matched Study.

BACKGROUND: The role of endoscopic resection (ER) in the management of subsets of clinical T1N0 gastric adenocarcinoma remains controversial. The aim of this study was to evaluate the outcome of ER versus gastrectomy in node-negative cT1a and cT1b gastric adenocarcinoma. METHODS: Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2927; ER: n = 1157, gastrectomy: n = 1770) and T1bN0 (n = 2915; ER: n = 474, gastrectomy: n = 2441) gastric adenocarcinoma. Propensity score matching and Cox multivariable analyses were used to account for treatment selection bias. RESULTS: ER for cT1a and cT1b cancers was performed more frequently over time. The rates of node-positive disease in patients with cT1a and cT1b gastric adenocarcinoma were 5% and 18%, respectively. In the matched cohort, gastrectomy was associated with increased survival compared with ER for cT1a cancers (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95; p = 0.013), and corresponding 5-year survival for gastrectomy and ER was 72% and 66%, respectively (p = 0.013). For cT1b cancers, gastrectomy had a significantly longer survival compared with ER (HR 0.77, 95% CI 0.63-0.93; p = 0.008), and the corresponding 5-year survival for gastrectomy and ER was 60% and 50%, respectively (p = 0.013). CONCLUSION: This study demonstrates ER is inferior in terms of long-term survival for clinical T1aN0 and T1bN0 gastric adenocarcinoma, despite current recommendations for ER in cT1 gastric cancers. Future research should seek to identify the subset of T1a and T1b cancers at low risk of nodal metastasis, and would thus maximally benefit from ER.

Does Cardiopulmonary Testing Help Predict Long-Term Survival After Esophagectomy?

BACKGROUND: Esophagectomy is associated with a high rate of morbidity and mortality. Preoperative cardiopulmonary fitness has been correlated with outcomes of major surgery. Variables derived from cardiopulmonary exercise testing (CPET) have been associated with postoperative outcomes. It is unclear whether preoperative cardiorespiratory fitness of patients undergoing esophagectomy is associated with long-term survival. This study aimed to evaluate whether any of the CPET variables routinely derived from patients with esophageal cancer may aid in predicting long-term survival after esophagectomy. METHODS: Patients undergoing CPET followed by trans-thoracic esophagectomy for esophageal cancer with curative intent between January 2013 and January 2017 from single high-volume center were retrospectively analyzed. The relationship between predictive co-variables, including CPET variables and survival, was studied with a Cox proportional hazard model. Receiver operation curve (ROC) analysis was performed to find cutoff values for CPET variables predictive of 3-year survival. RESULTS: The study analyzed 313 patients. The ventilatory equivalent for carbon dioxide (VE/VCO2) at the anerobic threshold was the only CPET variable independently predictive of long-term survival in the multivariable analysis (hazard ratio [HR], 1.049; 95% confidence interval [CI], 1.011-1.088; p = 0.011). Pathologic stages 3 and 4 disease was the other co-variable found to be independently predictive of survival. An ROC analysis of the VE/VCO2 failed to demonstrate a predictive cutoff value of 3-year survival (area under the curve, 0.564; 95% CI, 0.499-0.629; p = 0.056). CONCLUSIONS: A high VE/VCO2 before esophagectomy for malignant disease is an independent predictor of long-term survival and may be an important variable for clinicians to consider when counseling patients.

Evolution of Esophagectomy for Cancer Over 30 Years: Changes in Presentation, Management and Outcomes.

BACKGROUND: Esophageal cancer has seen a considerable change in management and outcomes over the last 30 years. Historically, the overall prognosis has been regarded as poor; however, the use of multimodal treatment and the integration of enhanced recovery pathways have improved short- and long-term outcomes. OBJECTIVE: The aim of this study was to evaluate the changing trends in presentation, management, and outcomes for patients undergoing surgical treatment for esophageal cancer over 30 years from a single-center, high-volume unit in the UK. PATIENTS AND METHODS: Data from consecutive patients undergoing esophagectomy for cancer (adenocarcinoma or squamous cell carcinoma) between 1989 and 2018 from a single-center, high-volume unit were reviewed. Presentation method, management strategies, and outcomes were evaluated. Patients were grouped into successive 5-year cohorts for comparison and evaluation of changing trends. RESULTS: Between 1989 and 2018, 1486 patients underwent esophagectomy for cancer. Median age was 65 years (interquartile range [IQR] 59-71) and 1105 (75%) patients were male. Adenocarcinoma constituted 1105 (75%) patients, and overall median survival was 29 months (IQR 15-68). Patient presentation changed, with epigastric discomfort now the most common presentation (70%). An improvement in mortality from 5 to 2% (p < 0.001) was seen over the time period, and overall survival improved from 22 to 56 months (p < 0.001); however, morbidity increased from 54 to 68% (p = 0.004). CONCLUSIONS: Long-term outcomes have significantly improved over the 30-year study period. In addition, mortality and length of stay have improved despite an increase in complications. The reasons for this are multifactorial and include the use of perioperative chemo(radio)therapy, the introduction of an enhanced recovery pathway, and improved patient selection.

Esophagectomy or Total Gastrectomy for Siewert 2 Gastroesophageal Junction (GEJ) Adenocarcinoma? A Registry-Based Analysis.

BACKGROUNDS: Due to a lack of randomized and large studies, the optimal surgical approach for Siewert 2 gastroesophageal junctional (GEJ) adenocarcinoma remains unknown. This population-based cohort study aimed to compare survival between esophagectomy and total gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma. METHODS: Data from the National Cancer Database (NCDB) from 2010 to 2016 was used to identify patients with non-metastatic Siewert 2 GEJ adenocarcinoma who received either esophagectomy (n = 999) or total gastrectomy (n = 8595). Propensity score-matching (PSM) and multivariable analyses were used to account for treatment selection bias. RESULTS: Comparison of the unmatched cohort's baseline demographics showed that the patients who received esophagectomy were younger, had a lower burden of medical comorbidities, and had fewer clinical positive lymph nodes. The patients in the unmatched cohort who received gastrectomy had a significantly shorter overall survival than those who received esophagectomy (median, 47 vs. 68 months [p < 0.001]; 5-year survival, 45 % vs. 53 %). After matching, gastrectomy was associated with significantly reduced survival compared with esophagectomy (median, 51 vs. 68 months [p < 0.001]; 5-year survival, 47 % vs. 53 %), which remained in the adjusted analyses (hazard ratio [HR], 1.22; 95 % confidence interval [CI], 1.09-1.35; p < 0.001). CONCLUSIONS: In this large-scale population study with propensity-matching to adjust for confounders, esophagectomy was prognostically superior to gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma despite comparable lymph node harvest, length of stay, and 90-day mortality. Adequately powered randomized controlled trials with robust surgical quality assurance are the next step in evaluating the prognostic outcomes of these surgical strategies for GEJ cancer.

Impact of Smoking Status on Perioperative Morbidity, Mortality, and Long-Term Survival Following Transthoracic Esophagectomy for Esophageal Cancer.

INTRODUCTION: Esophagectomy is a key component in the curative treatment of esophageal cancer. Little is understood about the impact of smoking status on perioperative morbidity and mortality and the long-term outcome of patients following esophagectomy. OBJECTIVE: This study aimed to evaluate morbidity and mortality according to smoking status in patients undergoing esophagectomy for esophageal cancer. METHODS: Consecutive patients undergoing two-stage transthoracic esophagectomy (TTE) for esophageal cancers (adenocarcinoma or squamous cell carcinoma) between January 1997 and December 2016 at the Northern Oesophagogastric Unit were included from a prospectively maintained database. The main explanatory variable was smoking status, defined as current smoker, ex-smoker, and non-smoker. The primary outcome was overall survival (OS), while secondary outcomes included perioperative complications (overall, anastomotic leaks, and pulmonary complications) and survival (cancer-specific survival [CSS], recurrence-free survival [RFS]). RESULTS: During the study period, 1168 patients underwent esophagectomy for cancer. Of these, 24% (n = 282) were current smokers and only 30% (n = 356) had never smoked. The median OS of current smokers was significantly shorter than ex-smokers and non-smokers (median 36 vs. 42 vs. 48 months; p = 0.015). However, on adjusted analysis, there was no significant difference in long-term OS between smoking status in the entire cohort. The overall complication rates were significantly higher with current smokers compared with ex-smokers or non-smokers (73% vs. 66% vs. 62%; p = 0.018), and there were no significant differences in anastomotic leaks and pulmonary complications between the groups. On subgroup analysis by receipt of neoadjuvant therapy and tumor histology, smoking status did not impact long-term survival in adjusted multivariable analyses. CONCLUSION: Although smoking is associated with higher rates of short-term perioperative morbidity, it does not affect long-term OS, CSS, and RFS following esophagectomy for esophageal cancer. Therefore, implementation of perioperative pathways to optimize patients may help reduce the risk of complications.

Chyle Leak Following Radical En Bloc Esophagectomy with Two-Field Nodal Dissection: Predisposing Factors, Management, and Outcomes.

BACKGROUND: Chyle leak is an uncommon complication following esophagectomy, accounting for significant morbidity and mortality; however, the optimal treatment for the chylothorax is still controversial. OBJECTIVE: The aim of this study was to evaluate the incidence, management, and outcomes of chyle leaks within a specialist esophagogastric cancer center. METHODS: Consecutive patients undergoing esophagectomy for esophageal cancers (adenocarcinoma or squamous cell carcinoma) between 1997 and 2017 at the Northern Oesophagogastric Unit were included from a contemporaneously maintained database. Primary outcome was overall survival, while secondary outcomes were overall complications, anastomotic leaks, and pulmonary complications. RESULTS: During the study period, 992 patients underwent esophagectomy for esophageal cancers, and 5% (n = 50) of them developed chyle leaks. There was no significant difference in survival in patients who developed a chyle leak compared with those who did not (median: 40 vs. 45 months; p = 0.60). Patients developing chyle leaks had a significantly longer length of stay in critical care (median: 4 vs. 2 days; p = 0.002), but no difference in total length of hospital stay. CONCLUSION: Chyle leak remains a complication following esophagectomy, with limited understanding on its pathophysiology in postoperative recovery. However, these data indicate chyle leak does not have a long-term impact on patients and does not affect long-term survival.

The impact of age on patients undergoing transthoracic esophagectomy for cancer.

To compare long-term and short-term outcomes in patients <70 years old with those ≥ 70 years old, who underwent transthoracic esophagectomy for carcinoma. With an ageing population more patients, with increasing co-morbidities are being diagnosed with potentially curable esophageal cancer. Concerns exist regarding offering older patients esophagectomy, conversely undue prejudice may exists that may prevent surgery being offered. Consecutive patients from a single unit between January 2000 and July 2016 that underwent trans-thoracic esophagectomy with or without neoadjuvant treatment for carcinoma were included. Short-term outcomes including morbidity, mortality, length of stay and long-term survival were compared between those <70 and those ≥ 70. This study identified 992 patients who underwent esophagectomy during the study period, of which 302 (30%) ≥ 70 years old. Greater proportion ≥ 70 years old had SCC (squamous cell carcinoma) (23%) than <70 (18%) (p = 0.07). Patients ≥ 70 years old were noted to have higher ASA Grade 3 (34% vs 25%, p = 0.004) and were less likely to receive neoadjuvant treatment (64% vs 45% p<0.001). Length of stay was longer in ≥ 70 (14 vs 17 days p<0.001), and there were more complications (63% vs 75% p<0.001). In hospital mortality was higher in ≥ 70 (2% vs 5% p = 0.026). Overall survival was 50 months in <70 vs 36 months in ≥ 70 (p = <0.001). In <70s with adenocarcinoma, overall survival was 52 months vs 35 months in the ≥ 70 (p<0.001). No significant difference in survival in patients with SCC, 49 months in <70 vs 54 months in ≥ 70 (p = 0.711). Increased peri-operative morbidity and mortality combined with the reduction in the long term survival in the over 70s cohort should be addressed when counselling patients undergoing curative resection for oesophageal cancer.

Prognostic Significance of Lymphatic, Venous and Perineural Invasion After Neoadjuvant Chemotherapy in Patients with Gastric Adenocarcinoma.

BACKGROUND: The significance of perineural (PNI), lymphatic (LI) and venous invasion (VI) in gastric cancer patients who have received neoadjuvant chemotherapy is unclear. The aim of this study is to determine the incidence and prognostic significance of LI, VI and PNI in these patients. PATIENTS AND METHODS: Consecutive patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy were reviewed. Presence of LI, VI and PNI was recorded and correlated with clinical outcomes. RESULTS: A total of 243 patients underwent gastrectomy after neoadjuvant therapy for gastric adenocarcinoma. LI was identified in 129 (53%), VI in 107 (44%) and PNI in 116 (48%) of patients. Presence of LI (HR, 2.95, CI 1.91-4.56), VI (HR, 2.66, CI 1.78-3.98) and PNI (HR, 3.85, CI 2.49-5.95) was associated with poorer survival (all p < 0.001). Multivariable analysis revealed that ypT stage (HR, 1.35, CI 1.05-1.74), ypN stage (HR, 1.53, CI 1.28-1.83) and PNI (HR, 2.11, CI 1.31-3.42) were independent predictors of survival. CONCLUSIONS: LI, VI and PNI are associated with poorer survival, with PNI having prognostic significance independent of lymph node status. These factors may be useful for further prognostication, in particular when multiple factors are present, and appear especially useful for prognostic stratification in patients with no nodal involvement.

Signet ring gastric and esophageal adenocarcinomas: characteristics and prognostic implications.

Controversy exists as to the relevance of the signet ring carcinoma (SRC) histological subtype of esophagogastric adenocarcinoma to long-term prognosis, with some studies reporting a worsened oncological outcome and others no clinically relevant impact. A retrospective analysis of outcomes of patients who underwent surgery with curative intent in two high-volume centers (2000-2015) was undertaken. Tumors were analyzed according to location (esophageal, junctional or gastric). Propensity score matching (PSM) analysis was used to match patients with signet ring histology to those without (195 SRC vs. 573 non-SRC), based on age, tumor location, use of neoadjuvant and adjuvant chemotherapy and pathological stage. A total of 2,500 patients with esophagogastric adenocarcinomas were treated, of whom 198 (7.9%) had signet ring histology. Signet ring tumors were more likely to have positive lymph nodes at pathological analysis (59% vs. 50%, P = 0.009). The 5-year survival rate for patients with early signet ring tumors (Stage 0/I/IIa) was 65% versus 85% for other early cancers (P < 0.003). Patients with esophageal signet ring tumors had a particularly poor prognosis with 23% 2-year survival and none alive at 5 years. With PSM, overall survival (OS) was significantly poorer in the signet ring group (44.3 ± 8.6 vs. 59.8 ± 8.5 months, 5-year OS 41% vs. 50%, P = 0.027). Signet ring cells within esophagogastric adenocarcinoma are associated with a poorer prognosis. Genomic studies to identify the composition of such tumors as well as identify strategies to improve treatment for this subtype are warranted.