A Systematic Review of Surgical and Pathological Outcomes in Patients With a CDH1 Mutation Undergoing Total Gastrectomy.

BACKGROUND: CDH1 (E-cadherin) genetic mutations are associated with a 30%-70% increased lifetime risk of hereditary diffuse gastric cancer (HDGC). Although prophylactic total gastrectomy (PTG) reduces long-term risk of gastric cancer, the associated morbidity and mortality remain unclear. This systematic review aims to characterise postoperative surgical outcomes in patients undergoing total gastrectomy. METHODS: A systematic literature search was performed for studies reporting endoscopic surveillance, surgical and pathological outcomes for patients with CDH1 mutation undergoing a total gastrectomy. RESULTS: Thirty-nine studies included 1849 patients, of which 96% had a CDH1 (n = 1777) or CTNNA1 (n = 3) mutation. Endoscopy outcomes were reported for 1640 patients. Cancer foci were identified in 32% (n = 523/1640) and 71% of these patients went on to have a total gastrectomy (n = 369/523). The remaining 78% of patients did not have cancer foci detected on endoscopy (n = 1117/1640). Of these patients, 62% underwent a total gastrectomy (n = 688/1117) and 81% were found to have cancer on surgical histology (n = 556/688). Pathological staging was reported for 790 patients undergoing surgery, of which 68% had pT1 disease (n = 537). Postoperative complications were reported for 430 patients across 23 studies, with the most common complications being anastomotic strictures (25%), anastomotic leaks (13%), wound infections (12%) and pulmonary complications (11%). Only one postoperative death was reported within 30 days. CONCLUSION: Rates of early cancers are high in CDH1 patients undergoing PTG, highlighting the need for improvement in reliable endoscopic surveillance. Although postoperative mortality in this surgical cohort remains low, high rates of postoperative complications warrant careful patient counselling.

Prevalence and Risk Factors for Malignant Nodal Involvement in Early esophago-gastric Adenocarcinoma: Results from the Multicenter Retrospective Congress Study (endosCopic resectiON, esophaGectomy or Gastrectomy For Early Esophagogastric Cancers).

OBJECTIVE: The aim of this study was to quantify LNM risk and outcomes following treatment of early esophago-gastric (EG) adenocarcinoma. BACKGROUND: The standard of care for early T1N0 EG cancer is endoscopic resection (ER). Radical surgical resection is recommended for patients perceived to be at risk of lymph node metastasis (LNM). Current models to select organ-preserving vs. surgical treatment are inconsistent. METHODS: CONGRESS is a UK-based multicentre retrospective cohort study. Patients diagnosed with clinical or pathological T1N0 EG adenocarcinoma from 2015-2022 were included. Outcomes and rates of LNM were assessed. Cox regression was performed to assess the impact of prognostic and treatment factors on overall survival. RESULTS: 1,601 patients from 26 centres were included, with median follow-up 32 months(IQR 14-53). 1285/1612(80.3%) underwent ER, 497/1601(31.0%) underwent surgery. Overall rate of LNM was 13.5%. On ER staging, tumour depth (T1bsm2-3 17.6% vs. T1a 7.1%), lymphovascular invasion (17.2% vs. 12.6%), or signet cells (28.6% vs. 13.0%) were associated with LNM. In multivariable regression analysis, these were not significantly associated with LNM rates or survival. Adjusting for demographic and tumour variables, surgery after ER was associated with significant survival benefit, HR 0.33(0.15-0.77),P=0.010. CONCLUSION: This large multicentre dataset suggests that early EG adenocarcinoma is associated with significant risk of LNM. This data is representative of current real clinical practice with ER-based staging, and suggests previously held beliefs regarding reliability of predictive factors for LNM may need to be reconsidered. Further research to identify patients who may benefit from organ-preserving vs. surgical treatment is urgently required.

Reconstruction Techniques and Associated Morbidity in Minimally Invasive Gastrectomy for Cancer - Insights from the GastroBenchmark and GASTRODATA databases.

OBJECTIVE/BACKGROUND: Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied. METHODS: MiTG and miDG patients were selected from 9356 oncological gastrectomies performed 2017-2021 in 44 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis. RESULTS: Three major anastomotic techniques (circular stapled (CS); linear stapled (LS); hand sewn (HS)), and three major bowel reconstruction types (Roux (RX); Billroth I (BI); Billroth II (BII)) were identified in miTG (n=878) and miDG (n=3334). Postoperative complications including AL (5.2% vs. 1.1%), overall (28.7% vs. 16.3%) and major morbidity (15.7% vs. 8.2%), as well as 90-day mortality (1.6% vs. 0.5%) were higher after miTG compared with miDG. After miTG, AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as predictive factor for AL, overall and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, RX 1.2%), overall (BI: 14.5%, BII: 15.0%, RX: 18.7%,) and major morbidity (BI: 7.9%, BII: 9.1%, RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, RY: 1.1%%) were not affected by bowel reconstruction. CONCLUSION: In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to surgeon's preference.

Novel Textbook Outcomes following emergency laparotomy: Delphi exercise.

BACKGROUND: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. METHODS: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1-5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. RESULTS: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into 'early' and 'longer-term'. For non-trauma patients the proposed early Textbook Outcome was 'Discharged from hospital without serious postoperative complications (Clavien-Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was 'Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien-Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)'. The longer-term Textbook Outcome for both non-trauma and trauma was 'Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year'. CONCLUSION: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data.

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 before esophagectomy was associated with poorer long-term survival. METHODS: This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches. RESULTS: A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic 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: 1.14-2.5) and propensity-matched analysis ( P =0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50 Gy dose groups (HR=1.9; 95% CI: 1.2-3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1-2.2). CONCLUSIONS: MIE was associated with improved overall survival compared with 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.

Predictors and Significance of Readmission after Esophagogastric Surgery: A Nationwide Analysis.

Objective: The aim of this study is to identify risk factors for readmission after elective esophagogastric cancer surgery and characterize the impact of readmission on long-term survival. The study will also identify whether the location of readmission to either the hospital that performed the primary surgery (index hospital) or another institution (nonindex hospital) has an impact on postoperative mortality. Background: Over the past decade, the center-volume relationship has driven the centralization of major cancer surgery, which has led to improvements in perioperative mortality. However, the impact of readmission, especially to nonindex centers, on long-term mortality remains unclear. Methods: This was a national population-based cohort study using Hospital Episode Statistics of adult patients undergoing esophagectomy and gastrectomy in England between January 2008 and December 2019. Results: This study included 27,592 patients, of which overall readmission rates were 25.1% (index 15.3% and nonindex 9.8%). The primary cause of readmission to an index hospital was surgical in 45.2% and 23.7% in nonindex readmissions. Patients with no readmissions had significantly longer survival than those with readmissions (median: 4.5 vs 3.8 years; P < 0.001). Patients readmitted to their index hospital had significantly improved survival as compared to nonindex readmissions (median: 3.3 vs 4.7 years; P < 0.001). Minimally invasive surgery and surgery performed in high-volume centers had improved 90-day mortality (odds ratio, 0.75; P < 0.001; odds ratio, 0.60; P < 0.001). Conclusion: Patients requiring readmission to the hospital after surgery have an increased risk of mortality, which is worsened by readmission to a nonindex institution. Patients requiring readmission to the hospital should be assessed and admitted, if required, to their index institution.

Navigating reflux disease after achalasia treatments: Balancing risks and benefits.

The peroral endoscopic myotomy (POEM) procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by achalasia. Alongside its success in alleviating dysphagia, concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully resolved. In this study, Nabi et al have comprehensively reviewed the topic of the prediction, prevention and management of gastroesophageal reflux after POEM. POEM is a purely endoscopic procedure which is usually performed without any anti-reflux procedure. Certain patients may be better served by a laparoscopic Heller's myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for them. This article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

A comparison of outcomes including bile duct injury of subtotal cholecystectomy versus open total cholecystectomy as bailout procedures for severe cholecystitis: A multicenter real-world study.

BACKGROUND: Dense inflammation obscuring the hepatocystic anatomy can hinder the ability to perform a safe standard laparoscopic cholecystectomy in severe cholecystitis, requiring use of a bailout procedure. We compared clinical outcomes of laparoscopic and open subtotal cholecystectomy against the traditional standard of open total cholecystectomy to identify the optimal bailout strategy for the difficult gallbladder. METHODS: A multicenter, multinational retrospective cohort study of patients who underwent bailout procedures for severe cholecystitis. Procedures were compared using one-way analysis of variance/Kruskal-Wallis tests and χ2 tests with multiple pairwise comparisons, maintaining a family-wise error rate at 0.05. Multiple multivariate linear/logistical regression models were created. RESULTS: In 11 centers, 727 bailout procedures were conducted: 317 laparoscopic subtotal cholecystectomies, 172 open subtotal cholecystectomies, and 238 open cholecystectomies. Baseline characteristics were similar among subgroups. Bile leak was common in laparoscopic and open fenestrating subtotal cholecystectomies, with increased intraoperative drain placements and postoperative endoscopic retrograde cholangiopancreatography(P < .05). In contrast, intraoperative bleeding (odds ratio = 3.71 [1.9, 7.22]), surgical site infection (odds ratio = 2.41 [1.09, 5.3]), intensive care unit admission (odds ratio = 2.65 [1.51, 4.63]), and length of stay (Δ = 2 days, P < .001) were higher in open procedures. Reoperation rates were higher for open reconstituting subtotal cholecystectomies (odds ratio = 3.43 [1.03, 11.44]) than other subtypes. The overall rate of bile duct injury was 1.1% and was not statistically different between groups. Laparoscopic subtotal cholecystectomy had a bile duct injury rate of 0.63%. CONCLUSION: Laparoscopic subtotal cholecystectomy is a feasible surgical bailout procedure in cases of severe cholecystitis where standard laparoscopic cholecystectomy may carry undue risk of bile duct injury. Open cholecystectomy remains a reasonable option.

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

Predictors of anastomotic leak and conduit necrosis after oesophagectomy: Results from the oesophago-gastric anastomosis audit (OGAA).

BACKGROUND: Both anastomotic leak (AL) and conduit necrosis (CN) after oesophagectomy are associated with high morbidity and mortality. Therefore, the identification of preoperative, modifiable risk factors is desirable. The aim of this study was to generate a risk scoring model for AL and CN after oesophagectomy. METHODS: Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018-December 2018. Definitions for AL and CN were those set out by the Oesophageal Complications Consensus Group. Univariate and multivariate analyses were performed to identify risk factors for both AL and CN. A risk score was then produced for both AL and CN using the derivation set, then internally validated using the validation set. RESULTS: This study included 2247 oesophagectomies across 137 hospitals in 41 countries. The AL rate was 14.2% and CN rate was 2.7%. Preoperative factors that were independent predictors of AL were cardiovascular comorbidity and chronic obstructive pulmonary disease. The risk scoring model showed insufficient predictive ability in internal validation (area under the receiver-operating-characteristic curve [AUROC] = 0.618). Preoperative factors that were independent predictors of CN were: body mass index, Eastern Cooperative Oncology Group performance status, previous myocardial infarction and smoking history. These were converted into a risk-scoring model and internally validated using the validation set with an AUROC of 0.775. CONCLUSION: Despite a large dataset, AL proves difficult to predict using preoperative factors. The risk-scoring model for CN provides an internally validated tool to estimate a patient's risk preoperatively.

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.

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.

Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom.

PURPOSE: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. METHODS: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. RESULTS: In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). CONCLUSION: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

Research protocol for the Paraesophageal hernia symptom tool, a prospective multi-center cohort study to identify the need and threshold for surgery and assess the symptom response to surgery.

Large hiatus hernias with a significant paraesophageal component (types II-IV) have a range of insidious symptoms. Management of symptomatic hernias includes conservative treatment or surgery. Currently, there is no paraesophageal hernia disease-specific symptom questionnaire. As a result, many clinicians rely on the health-related quality of life questionnaires designed for gastro-esophageal reflux disease (GORD) to assess patients with hiatal hernias pre- and postoperatively. In view of this, a paraesophageal hernia symptom tool (POST) was designed. This POST questionnaire now requires validation and assessment of clinical utility. Twenty-one international sites will recruit patients with paraesophageal hernias to complete a series of questionnaires over a five-year period. There will be two cohorts of patients-patients with paraesophageal hernias undergoing surgery and patients managed conservatively. Patients are required to complete a validated GORD-HRQL, POST questionnaire, and satisfaction questionnaire preoperatively. Surgical cohorts will also complete questionnaires postoperatively at 4-6 weeks, 6 months, 12 months, and then annually for a total of 5 years. Conservatively managed patients will repeat questionnaires at 1 year. The first set of results will be released after 1 year with complete data published after a 5-year follow-up. The main results of the study will be patient's acceptance of the POST tool, clinical utility of the tool, assessment of the threshold for surgery, and patient symptom response to surgery. The study will validate the POST questionnaire and identify the relevance of the questionnaire in routine management of paraesophageal hernias.

Treatment of anastomotic leak after oesophagectomy for oesophageal cancer: large, collaborative, observational TENTACLE cohort study.

BACKGROUND: Anastomotic leak is a severe complication after oesophagectomy. Anastomotic leak has diverse clinical manifestations and the optimal treatment strategy is unknown. The aim of this study was to assess the efficacy of treatment strategies for different manifestations of anastomotic leak after oesophagectomy. METHODS: A retrospective cohort study was performed in 71 centres worldwide and included patients with anastomotic leak after oesophagectomy (2011-2019). Different primary treatment strategies were compared for three different anastomotic leak manifestations: interventional versus supportive-only treatment for local manifestations (that is no intrathoracic collections; well perfused conduit); drainage and defect closure versus drainage only for intrathoracic manifestations; and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis. The primary outcome was 90-day mortality. Propensity score matching was performed to adjust for confounders. RESULTS: Of 1508 patients with anastomotic leak, 28.2 per cent (425 patients) had local manifestations, 36.3 per cent (548 patients) had intrathoracic manifestations, 9.6 per cent (145 patients) had conduit ischaemia/necrosis, 17.5 per cent (264 patients) were allocated after multiple imputation, and 8.4 per cent (126 patients) were excluded. After propensity score matching, no statistically significant differences in 90-day mortality were found regarding interventional versus supportive-only treatment for local manifestations (risk difference 3.2 per cent, 95 per cent c.i. -1.8 to 8.2 per cent), drainage and defect closure versus drainage only for intrathoracic manifestations (risk difference 5.8 per cent, 95 per cent c.i. -1.2 to 12.8 per cent), and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis (risk difference 0.1 per cent, 95 per cent c.i. -21.4 to 1.6 per cent). In general, less morbidity was found after less extensive primary treatment strategies. CONCLUSION: Less extensive primary treatment of anastomotic leak was associated with less morbidity. A less extensive primary treatment approach may potentially be considered for anastomotic leak. Future studies are needed to confirm current findings and guide optimal treatment of anastomotic leak after oesophagectomy.

Effect of Anastomotic Leak on Long-Term Survival After Esophagectomy: Multivariate Meta-analysis and Restricted Mean Survival Times Examination.

BACKGROUND: Anastomotic leak (AL) is a serious complication after esophagectomy. It is associated with prolonged hospital stay, increased costs, and increased risk for 90-day mortality. Controversy exists concerning the impact of AL on survival. This study was designed to investigate the effect of AL on long-term survival after esophagectomy for esophageal cancer. METHODS: PubMed, MEDLINE, Scopus, and Web of Science were searched through October 30, 2022. The included studies evaluated the effect of AL on long-term survival. Primary outcome was long-term overall survival. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. RESULTS: Thirteen studies (7118 patients) were included. Overall, 727 (10.2%) patients experienced AL. The RMSTD analysis shows that at 12, 24, 36, 48, and 60 months, patients not experiencing AL live an average of 0.7 (95% CI 0.2-1.2; p < 0.001), 1.9 (95% CI 1.1-2.6; p < 0.001), 2.6 (95% CI 1.6-3.7; p < 0.001), 3.4 (95% CI 1.9-4.9; p < 0.001), and 4.2 (95% CI 2.1-6.4; p < 0.001) months longer compared with those with AL, respectively. The time-dependent HRs analysis for AL versus no AL shows a higher mortality hazard in patients with AL at 3 (HR 1.94, 95% CI 1.54-2.34), 6 (HR 1.56, 95% CI 1.39-1.75), 12 (HR 1.47, 95% CI 1.24-1.54), and 24 months (HR 1.19, 95% CI 1.02-1.31). CONCLUSIONS: This study seems to suggest a modest clinical impact of AL on long-term OS after esophagectomy. Patients who experience AL seem to have a higher mortality hazard during the first 2 years of follow-up.