Predictors of textbook outcome following oesophagogastric cancer surgery.

Textbook outcome (TO) is a composite measure representing an ideal perioperative course, which has been utilized to assess the quality of care in oesophagogastric cancer (OGC) surgery. We aim to determine TO rates among OGC patients in a UK tertiary center, investigate predictors of TO attainment, and evaluate the relationship between TO and survival. A retrospective analysis of a prospectively collected departmental database between 2006 and 2021 was conducted. Patients that underwent radical OGC surgery with curative intent were included. TO attainment required margin-negative resection, adequate lymphadenectomy, uncomplicated postoperative course, and no hospital readmission. Predictors of TO were investigated using multivariable logistic regression. The association between TO and survival was evaluated using Kaplan-Meier analysis and Cox regression modeling. In sum, 667 esophageal cancer and 312 gastric cancer patients were included. TO was achieved in 35.1% of esophagectomy patients and 51.3% of gastrectomy patients. Several factors were independently associated with a low likelihood of TO attainment: T3 stage (odds ratio (OR): 0.41, 95% confidence interval (CI) [0.22-0.79], p = 0.008) and T4 stage (OR:0.26, 95% CI [0.08-0.72], p = 0.013) in the esophagectomy cohort and high BMI (OR:0.93, 95% CI [0.88-0.98], p = 0.011) in the gastrectomy cohort. TO attainment was associated with greater overall survival and recurrence-free survival in esophagectomy and gastrectomy cohorts. TO is a relevant quality metric that can be utilized to compare surgical performance between centers and investigate patients at risk of TO failure. Enhancement of preoperative care measures can improve TO rates and, subsequently, long-term survival.

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.

Surgical Approach does not Affect Return to Intended Oncologic Therapy Following Pancreaticoduodenectomy for Pancreatic Adenocarcinoma: A Propensity-Matched Study.

BACKGROUND: The effect of minimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic and robotic pancreaticoduodenectomy (LPD and RPD, respectively), on compliance and time to return to intended oncologic therapy (RIOT) for pancreatic ductal adenocarcinoma (PDAC) remains unknown. PATIENTS AND METHODS: Patients with nonmetastatic PDAC were analyzed in the National Cancer Database (NCDB). Three groups were matched per propensity score: open pancreaticoduodenectomy (OPD) and MIPD, LPD and RPD, and converted and nonconverted patients. RIOT rates and time to RIOT were examined. RESULTS: A total of 14,135 patients were included: 11,834 (83.7%) underwent OPD and 2301 (16.3%) underwent MIPD. After score matching, RIOT rates (67.2 vs. 65.3%; p = 0.112) and RIOT within 8 weeks (57.7 vs. 56.4%; p = 0.276) were similar among MIPD and OPD groups, and approach was not a significant predictor of RIOT on multivariable regression. Neither RIOT nor time to RIOT were different among LPD and RPD groups (63.9 vs. 67.0%, and 58.4 vs. 56.9%, respectively). Compared with LPD, RPD was associated with lower conversion rates (HR 0.519; p < 0.001), and conversion was associated with longer median time to RIOT (10 vs. 8 weeks; p = 0.041). CONCLUSION: In this national cohort, approach did not impact RIOT rates or time to RIOT for patients with PDAC. While conversion was associated with longer median time to RIOT, readiness to commence adjuvant therapy was similar for LPD and RPD.

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.

Benchmarking of minimally invasive distal pancreatectomy with splenectomy: European multicentre study.

BACKGROUND: Benchmarking is the process to used assess the best achievable results and compare outcomes with that standard. This study aimed to assess best achievable outcomes in minimally invasive distal pancreatectomy with splenectomy (MIDPS). METHODS: This retrospective study included consecutive patients undergoing MIDPS for any indication, between 2003 and 2019, in 31 European centres. Benchmarks of the main clinical outcomes were calculated according to the Achievable Benchmark of Care (ABC™) method. After identifying independent risk factors for severe morbidity and conversion, risk-adjusted ABCs were calculated for each subgroup of patients at risk. RESULTS: A total of 1595 patients were included. The ABC was 2.5 per cent for conversion and 8.4 per cent for severe morbidity. ABC values were 160 min for duration of operation time, 8.3 per cent for POPF, 1.8 per cent for reoperation, and 0 per cent for mortality. Multivariable analysis showed that conversion was associated with male sex (OR 1.48), BMI exceeding 30 kg/m2 (OR 2.42), multivisceral resection (OR 3.04), and laparoscopy (OR 2.24). Increased risk of severe morbidity was associated with ASA fitness grade above II (OR 1.60), multivisceral resection (OR 1.88), and robotic approach (OR 1.87). CONCLUSION: The benchmark values obtained using the ABC method represent optimal outcomes from best achievable care, including low complication rates and zero mortality. These benchmarks should be used to set standards to improve patient outcomes.

Adjuvant chemotherapy after neoadjuvant chemoradiation and proctectomy improves survival irrespective of pathologic response in rectal adenocarcinoma: a population-based cohort study.

BACKGROUND: This study sought to determine whether adjuvant chemotherapy (AC) compared to no AC (noAC) after neoadjuvant chemoradiation (CRT) and resection for rectal adenocarcinoma prolongs survival. Current guidelines from expert groups are conflicting, and data to support administering AC to patients who received neoadjuvant CRT are lacking. METHODS: A total of 19,867 patients met inclusion/exclusion criteria. Mean age was 58.6 ± 12.0 years, and 12,396 (62.4%) were males. Complete response (CR) was documented in 3801 (19.1%) patients and 8167 (41.1%) received AC. The cohort was stratified into pathological complete (pCR, N = 3801) and incomplete (pIR, N = 16,066) subgroups, and pIR further subcategorized into ypN0 (N = 10,191) and ypN + (N = 5875) subgroups. After propensity score matching, AC was associated with improved OS in the pCR subgroups (mean 139.1 ± 1.9 vs. 134.0 ± 2.2 months; p < 0.001), in pIR ypN0 subgroup (141.6 ± 1.5 vs. 129.9 ± 1.2 months, p < 0.001), and in pIR ypN + subgroup (155.9 ± 5.4 vs. 126.5 ± 7.6 months; p < 0.001). RESULTS: AC was associated with improved OS in patients who received neoadjuvant CRT followed by proctectomy for clinical stages II and III rectal adenocarcinoma. This effect persisted irrespective of pathological response status. CONCLUSIONS: AC following neoadjuvant CRT and surgery is associated with improved OS in patients with rectal adenocarcinoma. These findings warrant adoption of AC after neoadjuvant CRT and surgery for clinical stage II and III rectal adenocarcinoma.

Systematic review and meta-analysis of survival outcomes in T2a and T2b gallbladder cancers.

BACKGROUND: The 8th edition of AJCC TNM staging of Gallbladder cancer subdivided T2 stage into T2a and T2b based on tumour location. This meta-analysis aimed to investigate the long-term outcomes in T2a and T2b gallbladder cancers. METHODS: Literature search of Medline, Web of science, Embase and Cochrane databases was performed. Study characteristics, survival and recurrence data were extracted for meta-analysis of effect estimates and of individual patient data. RESULTS: Fifteen retrospective studies (2531 patients, T2a = 1332, T2b = 199) were included in the meta-analysis. Overall survival (OS) was significantly worse in patients with T2b compared to T2a tumours (HR 2.18, 95% CI 1.67-2.86, p < 0.0001). Meta-analysis of individual patient data (n = 629) showed similar results (HR 1.92, 95% CI 1.43-2.58, p < 0.00001). Patients with T2b tumours had higher risk of recurrence compared to T2a (OR 3.19, 95% CI 1.40-7.28, p = 0.006) and were more likely to receive adjuvant chemotherapy (OR 1.76, 95% CI 1.12-2.84, p = 0.014). Liver resection improved OS in T2b tumours (HR 2.99, CI 1.73-5.16, p < 0.0001). CONCLUSION: T2b gallbladder tumours have worse overall survival and increase risk of recurrence compared to T2a. Liver resection appears to improve OS in patients with T2b tumours. However, high quality multicenter data is required to confirm these results.

Survival benefit with adjuvant radiotherapy after resection of distal cholangiocarcinoma: A propensity-matched National Cancer Database analysis.

BACKGROUND: No convincing evidence for the benefit of adjuvant radiotherapy (RT) following resection of distal cholangiocarcinoma (dCCA) exists, especially for lower-risk (margin- or node-negative) disease. Hence, the association of adjuvant RT on survival after surgical resection of dCCA was compared with no adjuvant RT (noRT). METHODS: Using National Cancer Database data from 2004 to 2016, patients undergoing pancreatoduodenectomy for nonmetastatic dCCA were identified. Patients with neoadjuvant RT and chemotherapy and survival <6 months were excluded. Propensity score matching was used to account for treatment-selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of adjuvant RT with survival. RESULTS: Of 2162 (34%) adjuvant RT and 4155 (66%) noRT patients, 1509 adjuvant RT and 1509 noRT patients remained in the cohort after matching. The rates of node-negative disease (N0), node-positive disease (N+), and unknown node status (Nx) were 39%, 51%, and 10%, respectively. After matching, adjuvant RT was associated with improved survival (median, 29.3 vs 26.8 months; P < .001), which remained after multivariable adjustment (HR, 0.86; 95% CI, 0.80-0.93; P < .001). Multivariable interaction analyses showed this benefit was seen irrespective of nodal status (N0: HR, 0.77; 95% CI, 0.66-0.89; P < .001; N+: HR, 0.79; 95% CI, 0.71-0.89; P < .001) and margin status (R0: HR, 0.58; 95% CI, 0.50-0.67; P < .001; R1: HR, 0.87; 95% CI, 0.78-0.96; P = .007). Stratified analyses by nodal and margin status demonstrated consistent results. CONCLUSIONS: Adjuvant RT after dCCA resection was associated with a survival benefit in patients, even in patients with margin- or node-negative resections. Adjuvant RT should be considered routinely irrespective of margin and nodal status after resection for dCCA. LAY SUMMARY: Adjuvant radiotherapy after resection of distal cholangiocarcinoma was associated with a survival benefit in patients, even in patients with margin-negative or node-negative resections. Adjuvant radiotherapy should be considered routinely irrespective of margin and nodal status after resection of distal cholangiocarcinoma.

Association of Adjuvant Radiotherapy With Survival After Margin-negative Resection of Pancreatic Ductal Adenocarcinoma: A Propensity-matched National Cancer Database (NCDB) Analysis.

INTRODUCTION: There is conflicting evidence for the benefit of adjuvant radiotherapy (RT) after resection of pancreatic ductal adenocarcinoma (PDAC), especially for margin-negative (R0) resections. We aimed to evaluate the association of adjuvant RT with survival after R0 resection of PDAC. METHODS: Using National Cancer Database (NCDB) data from 2004 to 2013, we identified patients with R0 resection of nonmetastatic PDAC. Patients with neoadjuvant radiotherapy and chemotherapy and survival <6 months were excluded. Propensity score matching was used to account for treatment selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of RT with survival. RESULTS: Of 4547 (36%) RT and 7925 (64%) non-RT patients, 3860 RT and 3860 non-RT patients remained in the cohort after matching. Clinicopathologic and demographic variables were well balanced after matching. Lymph node metastases were present in 68% (44% N1, 24% N2). After matching, RT was associated with higher survival (median 25.8 vs 23.9 mo, 5-yr 27% vs 24%, P < 0.001). After multivariable adjustment, RT remained associated with a survival benefit (HR 0.89, 95% CI 0.84-0.94, P < 0.001). Stratified and multivariable interaction analyses showed that this benefit was restricted to patients with node-positive disease: N1 (HR: 0.68, CI95%: 0.62-0.76, P = 0.007) and N2 (HR: 0.59, CI95%: 0.54-0.64, P = 0.04). CONCLUSIONS: In this large retrospective cohort study, adjuvant RT after R0 PDAC resection was associated with a survival benefit in patients with node-positive disease. Adjuvant RT should be considered after R0 resection of PDAC with node-positive disease.

Neoadjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma is Associated with Lower Post-Pancreatectomy Readmission Rates: A Population-Based Cohort Study.

INTRODUCTION: Despite neoadjuvant chemotherapy (NAC) being increasingly utilized and possibly associated with improved oncological outcomes, the impact of NAC on textbook outcomes following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) remains debated. METHODS: A retrospective review of the National Cancer Database of patients undergoing resection of non-metastatic PDAC from 2004 to 2016 was performed. Propensity score matching was used to account for treatment selection bias in patients with and without NAC (noNAC). A multivariable binary logistic regression model was used to analyze the association of NAC with length of stay (LOS), 30-day readmission, and 30- and 90-day mortality. RESULTS: Of 7975 (11%) NAC patients and 65,338 (89%) noNAC patients, 2911 NAC and 2911 noNAC patients remained in the cohort after matching. Clinicopathologic and demographic variables were well-balanced after matching. After matching, NAC was associated with significantly lower rates of 30-day readmission (5.5% vs. 7.4%; p = 0.006), which remained after multivariable adjustment (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.60-0.92; p = 0.006). There were no significant differences in LOS and 30- and 90-day mortality in patients receiving NAC and noNAC. Stratified analyses by surgery type (i.e. pancreaticoduodenectomy [PD] and distal pancreatectomy [DP]) demonstrated consistent results. CONCLUSION: Receipt of NAC in PDAC patients undergoing DP or PD is associated with lower readmission rates and does not otherwise compromise short-term outcomes. These data reaffirm the safety of strategies incorporating NAC and is important to consider when devising policies aimed at quality improvement in achieving textbook outcomes.

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.

Adjuvant Chemotherapy Associated with Survival Benefit Following Neoadjuvant Chemotherapy and Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Population-Based Cohort Study.

BACKGROUND: Data supporting the routine use of adjuvant chemotherapy (AC) compared with no AC (noAC) following neoadjuvant chemotherapy (NAC) and resection for pancreatic ductal adenocarcinoma (PDAC) are lacking. This study aimed to determine whether AC improves long-term survival in patients receiving NAC and resection. METHODS: Patients receiving resection for PDAC following NAC from 2004 to 2016 were identified from the National Cancer Data Base (NCDB). Patients with a survival rate of < 6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression analysis were performed to account for selection bias and analyze the impact of AC on overall survival. RESULTS: Of 4449 (68%) noAC patients and 2111 (32%) AC patients, 2016 noAC patients and 2016 AC patients remained after PSM. After matching, AC was associated with improved survival (median 29.4 vs. 24.9 months; p < 0.001), which remained after multivariable adjustment (HR 0.81, 95% confidence interval [CI] 0.75-0.88; p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (hazard ratio [HR] 0.80, 95% CI 0.72-0.90; p < 0.001), N1 (HR 0.76, 95% CI 0.67-0.86; p < 0.001), R0 margin status (HR 0.82, 95% CI 0.75-0.89; p < 0.001), R1 margin status (HR 0.77, 95% CI 0.64-0.93; p = 0.007), no neoadjuvant radiotherapy (NART; HR 0.84, 95% CI 0.74-0.96; p = 0.009), and use of NART (HR 0.80, 95% CI 0.73-0.88; p < 0.001). Stratified analysis by nodal, margin, and NART status demonstrated consistent results. CONCLUSION: AC following NAC and resection is associated with improved survival, even in margin-negative and node-negative disease. These findings suggest completing planned systemic treatment should be considered in all resected PDACs previously treated with NAC.

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.

Effect of anastomotic leaks on long-term survival after oesophagectomy for oesophageal cancer: systematic review and meta-analysis.

INTRODUCTION: Long-term survival after curative surgery for oesophageal cancer surgery remains poor, and the prognostic impact of anastomotic leak (AL) remains unknown. A meta-analysis was conducted to investigate the impact of AL on long-term survival. METHODS: A systematic electronic search for articles was performed for studies published between 2001 and 2020 evaluating the long-term oncological impact of AL. Meta-analysis was performed using the DerSimonian-Laird random-effects model to compute hazard ratios and 95% confidence intervals. RESULTS: Nineteen studies met the inclusion criteria, yielding a total of 9885 patients. Long-term survival was significantly reduced after AL (HR: 1.79, 95% CI: 1.33-2.43). AL was associated with significantly reduced overall survival in studies within hospital volume Quintile 1 (HR: 1.35, 95% CI: 1.12-1.63) and Quintile 2 (HR: 1.83, 95% CI: 1.35-2.47). However, no significant association was found for studies within Quintile 3 (HR: 2.24, 95% CI: 0.85-5.88), Quintile 4 (HR: 2.59, 95% CI: 0.67-10.07), and Quintile 5 (HR: 1.29, 95% CI: 0.92-1.81). AL was significantly associated with poor long-term survival in patients with associated overall Clavien Dindo Grades 1-5 (HR: 2.17, 95% CI: 1.31-3.59) and severe Clavien Dindo Grades 3-5 (HR: 1.42, 95% CI: 1.14-1.78) complications. CONCLUSIONS: AL has a negative prognostic impact on long-term survival after restorative resection of oesophageal cancers, particularly in low-volume centers. Future efforts must be focused on strategies to minimize the septic and immunological response to AL with early recognition and treatment thus reducing the impact on 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.

Long-term survival after minimally invasive resection versus open pancreaticoduodenectomy for periampullary cancers: a systematic review, meta-analysis and meta-regression.

BACKGROUND: It remains unclear whether minimally invasive pancreaticoduodenectomy (MIPD) and open pancreaticoduodenectomy (OPD) influences long-term survival in periampullary cancers. This review aims evaluate long-term survival between MIPD and OPD for periampullary cancers. METHODS: A systematic review was performed to identify studies comparing long-term survival after MIPD and OPD. The I2 test was used to test for statistical heterogeneity and publication bias using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year survival, and disease-specific 5-year and 3-year survival. Meta-regression was performed for the 5-year and 3-year survival outcomes with adjustment for study (region, design, case matching), hospital (centre volume), patient (ASA grade, gender, age), and tumor (stage, neoadjuvant therapy, subtype (i.e. ampullary, distal bile duct, duodenal, pancreatic)). Sensitivity analyses performed on studies including pancreatic ductal adenocarcinoma (PDAC) only. RESULTS: The review identified 31 relevant studies. Among all 58,622 patients, 8716 (14.9%) underwent MIPD and 49,875 (85.1%) underwent OPD. Pooled analysis revealed similar 5-year overall survival after MIPD compared with OPD (HR: 0.78, 95% CI 0.50-1.22, p = 0.2). Meta-regression indicated case matching, and ASA Grade II and III as confounding covariates. The statistical heterogeneity was limited (I2 = 12, χ2 = 0.26) and the funnel plot was symmetrical both according to visual and statistical testing (Egger test = 0.32). Sensitivity subset analyses for PDAC demonstrated similar 5-year overall survival after MIPD compared with OPD (HR 0.69, 95% CI: 0.32-1.50, p = 0.3). CONCLUSION: Long-term survival after MIPD is non-inferior to OPD. Thus, MIPD can be recommended as a standard surgical approach for periampullary cancers.