Cancer-related fatigue trajectories up to 5 years after curative treatment for oesophageal cancer.

BACKGROUND: Whether cancer-related fatigue develops differently after curative-intended oesophageal cancer treatment and the related modifiable factors are unclear. METHODS: This population-based and longitudinal cohort included 409 oesophageal cancer patients who underwent curative oesophagectomy in 2013-2020 in Sweden. The main outcome was cancer-related fatigue trajectories with measurements at 1, 1.5, 2, 2.5, 3, 4 and 5 years postoperatively by validated EORTC QLQ-FA12 questionnaire, and analysed using growth mixture models. Weighted logistic regressions provided odds ratios (OR) with 95% confidence intervals (95% CI) for underlying sociodemographic, clinical, and patient-reported outcome factors in relation to the identified trajectories. RESULTS: Two distinct overall cancer-related fatigue trajectories were identified: low level of persistent fatigue and high level of increasing fatigue, with 64% and 36% of patients, respectively. The odds of having high level of fatigue trajectory were increased by Charlson comorbidity index (≥ 2 versus 0: OR = 2.52, 95% CI 1.07-5.94), pathological tumour Stage (III-IV versus 0-I: OR = 2.52, 95% CI 1.33-4.77), anxiety (OR = 7.58, 95% CI 2.20-26.17), depression (OR = 15.90, 95% CI 4.44-56.93) and pain (continuous score: OR = 1.02, 95% CI 1.01-1.04). CONCLUSIONS: Long-term trajectories with high level of increasing cancer-related fatigue and the associated modifiable factors were identified after oesophageal cancer treatment. The results may facilitate early identification and targeted intervention for such high-risk patients.

Risk of Postoperative Ischemic Stroke and Myocardial Infarction in Patients Operated for Cancer.

BACKGROUND: Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this study is to assess the risk of arterial ischemic events during the first year after oncological surgery. METHODS: We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge. RESULTS: The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24-9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22-7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87-0.93) for myocardial infarction and 1.02 (95% CI 0.99-1.05) for ischemic stroke. CONCLUSIONS: We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects.

An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

Management and outcomes in a consecutive series of patients with aero-digestive fistula at a tertiary gastro-esophageal surgery center.

Aerodigestive fistula (ADF) is defined as a pathological connection between the upper digestive tract and the airway. ADF is associated with high morbidity and mortality and management is often complex. A cohort study including all patients admitted with ADF 2004-2022 at a single tertiary esophageal surgery center was performed based on prospectively collected administrative data and retrospectively collected electronic patient chart data,. Patient demographics, performance status, comorbidity, fistula characteristics, management, and outcomes in terms of morbidity and mortality were assessed in patients with ADF of three distinct types: (i) tumor overgrowth-related, (ii) various benign etiologies, and (iii) post-esophagectomy. Sixty-one patients with ADF were included in the study, 33 (54.1%) tumor overgrowth-related, six (9.8%) benign and 22 (36.1%) post-esophagectomy. In the post-esophagectomy group 15 out of 22 (68.2%) patients were diagnosed with anastomotic leakage prior to ADF diagnosis. Self-expandable metallic stents (SEMS) were used for temporary fistula sealing in 59 out of 61 (96.7%) patients, of which most received stents in both the digestive tract and airway. Temporary fistula sealing with stents was successful enabling discharge from hospital in 47 out of 59 (79.7%) patients. Definitive ADF repair was performed in 16 (26.2%) patients, of which one (6.3%) died within 90-days and 15 could be discharged home with permanently sealed fistulas. ADF is a complex condition associated with high mortality, which often requires multiple advanced interventions. SEMS can be applied in the airway and simultaneously in the digestive tract to temporarily seal the ADF as bridge to definitive surgical repair.

Randomized controlled trial of nasogastric tube use after esophagectomy: study protocol for the kinetic trial.

Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.

Western European Variation in the Organization of Esophageal Cancer Surgical Care.

Reasons for structural and outcome differences in esophageal cancer surgery in Western Europe remain unclear. This questionnaire study aimed to identify differences in the organization of esophageal cancer surgical care in Western Europe. A cross-sectional international questionnaire study was conducted among upper gastrointestinal (GI) surgeons from Western Europe. One surgeon per country was selected based on scientific output and active membership in the European Society for Diseases of the Esophagus or (inter)national upper GI committee. The questionnaire consisted of 51 structured questions on the structural organization of esophageal cancer surgery, surgical training, and clinical audit processes. Between October 2021 and October 2022, 16 surgeons from 16 European countries participated in this study. In 5 countries (31%), a volume threshold was present ranging from 10 to 26 annual esophagectomies, in 7 (44%) care was centralized in designated centers, and in 4 (25%) no centralizing regulations were present. The number of centers performing esophageal cancer surgery per country differed from 4 to 400, representing 0.5-4.9 centers per million inhabitants. In 4 countries (25%), esophageal cancer surgery was part of general surgical training and 8 (50%) reported the availability of upper GI surgery fellowships. A national audit for upper GI surgery was present in 8 (50%) countries. If available, all countries use the audit to monitor the quality of care. Substantial differences exist in the organization and centralization of esophageal cancer surgical care in Western Europe. The exchange of experience in the organizational aspects of care could further improve the results of esophageal cancer surgical care in Europe.

Extent of Lymphadenectomy and Long-term Survival in Esophageal Cancer.

OBJECTIVE: To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenec-tomy. SUMMARY OF BACKGROUND DATA: There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer. METHODS: This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors. RESULTS: Among 2306 patients, the second (4-8 nodes), seventh (21-24 nodes) and eighth decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the first decile [hazard ratio (HR) = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively]. In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8. CONCLUSION: Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.

An International Multicenter Study Exploring Whether Surveillance After Esophageal Cancer Surgery Impacts Oncological and Quality of Life Outcomes (ENSURE).

OBJECTIVE: To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer. SUMMARY BACKGROUND DATA: Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence. METHODS: European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009-2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed. RESULTS: Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12-0.25]) and increased tumor-directed therapy (OR 2.09 [1.58-2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89-1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47-0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58-0.89]). IS was associated with greater anxiety ( P =0.016), but similar overall HRQL. CONCLUSIONS: IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding.

Neoadjuvant Chemoradiotherapy Versus Chemotherapy for the Treatment of Locally Advanced Esophageal Adenocarcinoma in the European Multicenter ENSURE Study.

OBJECTIVE: This study aimed to compare clinicopathologic, oncologic, and health-related quality of life (HRQL) outcomes following neoadjuvant chemoradiation (nCRT) and chemotherapy (nCT) in the ENSURE international multicenter study. BACKGROUND: nCT and nCRT are the standards of care for locally advanced esophageal cancer (LAEC) treated with curative intent. However, no published randomized controlled trial to date has demonstrated the superiority of either approach. METHODS: ENSURE is an international multicenter study of consecutive patients undergoing surgery for LAEC (2009-2015) across 20 high-volume centers (NCT03461341). The primary outcome measure was overall survival (OS), secondary outcomes included histopathologic response, recurrence pattern, oncologic outcome, and HRQL in survivorship. RESULTS: A total of 2211 patients were studied (48% nCT, 52% nCRT). pCR was observed in 4.9% and 14.7% ( P <0.001), with R0 in 78.2% and 94.2% ( P <0.001) post nCT and nCRT, respectively. Postoperative morbidity was equivalent, but in-hospital mortality was independently increased [hazard ratio (HR)=2.73, 95% CI: 1.43-5.21, P= 0.002] following nCRT versus nCT. Probability of local recurrence was reduced (odds ratio=0.71, 95% CI: 0.54-0.93, P =0.012), and distant recurrence-free survival time reduced (HR=1.18, 95% CI: 1.02-1.37, P =0.023) after nCRT versus nCT, with no difference in OS among all patients (HR=1.10, 95% CI: 0.98-1.25, P =0.113). On subgroup analysis, patients who underwent R0 resection following nCT as compared with nCRT had improved OS (median: 60.7 months, 95% CI: 49.5-71.8 vs 40.8 months, 95% CI: 42.8-53.4, P <0.001). CONCLUSIONS: In this European multicenter study, nCRT compared with nCT was associated with reduced probability of local recurrence but reduced distant recurrence-free survival for patients with LAEC, without differences in OS. These data support tailored patient-specific decision-making in the overall approach to achieving optimum outcomes in LAEC.

Surgical Techniques and Related Perioperative Outcomes After Robot-assisted Minimally Invasive Gastrectomy (RAMIG): Results From the Prospective Multicenter International Ugira Gastric Registry.

OBJECTIVE: To gain insight in global practice of RAMIG and evaluated perioperative outcomes using an international registry. BACKGROUND: The techniques and perioperative outcomes of robot-assisted minimally invasive gastrectomy (RAMIG) for gastric cancer vary substantially in literature. METHODS: Prospectively registered RAMIG-cases for gastric cancer (≥10 per center) were extracted from 25 centers in Europe, Asia and South-America. Techniques for the resection, reconstruction, anastomosis and lymphadenectomy were analyzed, and related to perioperative surgical and oncological outcomes. Complications were uniformly defined by the Gastrectomy Complications Consensus Group. RESULTS: Between 2020-2023, 759 patients underwent total (n=272), distal (n=465) or proximal (n=22) gastrectomy (RAMIG). After total gastrectomy with Roux-en-Y-reconstruction, anastomotic leakage rates were 8% with hand-sewn (n=9/111) and 6% with linear stapled anastomoses (n=6/100). After distal gastrectomy with Roux-en-Y (67%) or Billroth-II-reconstruction (31%), anastomotic leakage rates were 3% with linear stapled (n=11/433) and 0% with hand-sewn anastomoses (n=0/26). Extent of lymphadenectomy consisted of D1+ (28%), D2 (59%) or D2+ (12%). Median nodal harvest yielded 31 nodes [IQR 21-47] after total and 34 nodes [IQR 24-47] after distal gastrectomy. R0-resection rates were 93% after total and 96% distal gastrectomy. Hospital stay was 9 days after total and distal gastrectomy, and was 3 days shorter without perianastomotic drains versus routine drain placement. Postoperative 30-day mortality was 1%. CONCLUSIONS: This large multicenter study provided a worldwide overview of current RAMIG-techniques with their respective perioperative outcomes. These outcomes demonstrated high surgical quality, set a quality standard for RAMIG and can be considered an international reference for surgical standardization.

Impact of Laparoscopic Gastrectomy on the Completion Rate of the Perioperative Chemotherapy Regimen in Gastric Cancer: A Swedish Nationwide Study.

BACKGROUND: Omission of prescheduled chemotherapy following surgery for gastric cancer is a frequent clinical problem. This study examined whether laparoscopic gastrectomy (LG) had a positive impact on compliance with adjuvant chemotherapy compared with open (OG). METHODS: Patients with cT2-4aN0-3M0 adenocarcinoma treated with gastrectomy and perioperative chemotherapy between 2015 and 2020 were identified in the Swedish national register. Additional information regarding chemotherapy was retrieved from medical records. Regression models were used to investigate the association between surgical approach and the following outcomes: initiation of adjuvant chemotherapy, modification, and time interval from surgery to start of treatment. RESULTS: A total of 247 patients were included (121 OG and 126 LG, conversion rate 11%), of which 71.3% had performance status ECOG 0 and 77.7% clinical stage II/III. In total, 86.2% of patients started adjuvant chemotherapy, with no significant difference between the groups (LG 88.1% vs OG 84.3%, p = 0.5). Reduction of chemotherapy occurred in 37.4% of patients and was similar between groups (LG 39.4% vs OG 35.1%, p = 0.6), as was the time interval from surgery. In multivariable analysis, LG was not associated with the probability of starting adjuvant chemotherapy (OR 1.36, p = 0.4) or the need for reduction (OR 1.29, p = 0.4). Conversely, major complications had a significant, negative impact on both outcomes. CONCLUSIONS: This nationwide study demonstrated a high rate of adjuvant chemotherapy initiation after curative intended surgery for gastric cancer. A beneficial effect of LG compared with OG on the completion rate was not evident.

Endoscopic vacuum therapy for esophageal perforation: a multicenter retrospective cohort study.

BACKGROUND : Endoscopic vacuum therapy (EVT) is a novel treatment for esophageal perforations. This study aimed to describe initial experience with EVT of esophageal perforations due to iatrogenic cause, Boerhaave syndrome, or other perforations not related to prior upper gastrointestinal surgery. METHODS : Data from patients treated with EVT for esophageal perforation at five hospitals in three European countries, between January 2018 and October 2021, were retrospectively collected. The primary end point was successful defect closure by EVT, with or without the use of other endoscopic treatment modalities. Secondary end points included mortality and adverse events. RESULTS : 27 patients were included (median age 71 years). The success rate was 89 % (24/27, 95 %CI 77-100). EVT failed in three patients: two deceased during EVT (septic embolic stroke, pulmonary embolism) and one underwent esophagectomy due to a persisting defect. Two adverse events occurred: one iatrogenic defect expansion during sponge exchange and one hemorrhage during sponge removal. Median treatment duration was 12 days (interquartile range [IQR] 6-16) with 1 sponge exchange (IQR 1-3). CONCLUSION : EVT is a promising organ-preserving treatment for esophageal perforations, with a success rate of 89 %. More experience with the technique and indications will likely improve success rates.

Improved survival after laparoscopic compared to open gastrectomy for advanced gastric cancer: a Swedish population-based cohort study.

BACKGROUND: Laparoscopic gastrectomy is increasingly used for the treatment of locally advanced gastric cancer but concerns remain whether similar results can be obtained compared to open gastrectomy, especially in Western populations. This study compared the short-term postoperative, oncological and survival outcomes following laparoscopic versus open gastrectomy based on data from the Swedish National Register for Esophageal and Gastric Cancer. METHODS: Patients who underwent surgery with curative intent for adenocarcinoma of the stomach or gastroesophageal junction Siewert type III from 2015 to 2020 were identified, and 622 patients with cT2-4aN0-3M0 tumors were included. The impact of surgical approach on short-term outcomes was assessed using multivariable logistic regression. Long-term survival was compared using multivariable Cox regression. RESULTS: In total, 350 patients underwent open and 272 laparoscopic gastrectomy, of which 12.9% were converted to open surgery. The groups were similar regarding distribution of clinical disease stage (27.6% stage I, 46.0% stage II, and 26.4% stage III). Neoadjuvant chemotherapy was administered to 52.7% of the patients. There was no difference in the rate of postoperative complications, but laparoscopic approach was associated with lower 90 day mortality (1.8 vs 4.9%, p = 0.043). The median number of resected lymph nodes was higher after laparoscopic surgery (32 vs 26, p < 0.001), while no difference was found in the rate of tumor-free resection margins. Better overall survival was observed after laparoscopic gastrectomy (HR 0.63, p < 0.001). CONCLUSIONS: Laparoscopic gastrectomy can be safely preformed for advanced gastric cancer and is associated with improved overall survival compared to open surgery.

Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial.

BACKGROUND: Adequate lymphadenectomy is an important step in gastrectomy for cancer, with a modified D2 lymphadenectomy being recommended for advanced gastric cancers. When assessing a novel technique for the treatment of gastric cancer, lymphadenectomy should be non-inferior. The aim of this study was to assess completeness of lymphadenectomy and distribution patterns between open total gastrectomy (OTG) and minimally invasive total gastrectomy (MITG) in the era of peri-operative chemotherapy. METHODS: This is a retrospective analysis of the STOMACH trial, a randomized clinical trial in thirteen hospitals in Europe. Patients were randomized between OTG and MITG for advanced gastric cancer after neoadjuvant chemotherapy. Three-year survival, number of resected lymph nodes, completeness of lymphadenectomy, and distribution patterns were examined. RESULTS: A total of 96 patients were included in this trial and randomized between OTG (49 patients) and MITG (47 patients). No difference in 3-year survival was observed, this was 57.1% in OTG group versus 46.8% in MITG group (P = 0.186). The mean number of examined lymph nodes per patient was 44.3 ± 16.7 in the OTG group and 40.7 ± 16.3 in the MITG group (P = 0.209). D2 lymphadenectomy of 71.4% in the OTG group and 74.5% in the MITG group was performed according to the surgeons; according to the pathologist compliance to D2 lymphadenectomy was 30% in the OTG group and 36% in the MITG group. Tier 2 lymph node metastases (stations 7-12) were observed in 19.6% in the OTG group versus 43.5% in the MITG group (P = 0.024). CONCLUSION: No difference in 3-year survival was observed between open and minimally invasive gastrectomy. No differences were observed for lymph node yield and type of lymphadenectomy. Adherence to D2 lymphadenectomy reported by the pathologist was markedly low.

CRP as an early indicator for anastomotic leakage after esophagectomy for cancer: a single tertiary gastro-esophageal center study.

PURPOSE: To determine the relationship between postoperative C-reactive protein (CRP) as an early indicator of anastomotic leakage (AL) after esophagectomy for esophageal cancer. METHODS: We reviewed patients diagnosed with esophageal or esophagogastric junctional cancer who underwent esophagectomy between 2006 and 2022 at the Karolinska University Hospital, Stockholm, Sweden. Multivariable logistic regression models estimated relative risk for AL by calculating the odds ratio (OR) with a 95% confidence interval (CI). The cut-off values for CRP were based on the maximum Youden's index using receiver operating characteristic curve analysis. RESULTS: In total, 612 patients were included, with 464 (75.8%) in the non-AL (N-AL) group and 148 (24.2%) in the AL group. Preoperative body mass index and the proportion of patients with the American Society of Anesthesiologists physical status classification 3 were significantly higher in the AL group than in the N-AL group. The median day of AL occurrence was the postoperative day (POD) 8. Trends in CRP levels from POD 2 to 3 and POD 3 to 4 were significantly higher in the AL than in the N-AL group. An increase in CRP of ≥ 4.65% on POD 2 to 3 was an independent risk factor for AL with the highest OR of 3.67 (95% CI 1.66-8.38, p = 0.001) in patients with CRP levels on POD 2 above 211 mg/L. CONCLUSION: Early changes in postoperative CRP levels may help to detect AL early following esophageal cancer surgery.

Long-term Survival in Esophageal Cancer After Minimally Invasive Esophagectomy Compared to Open Esophagectomy.

OBJECTIVE: To examine 5-year survival in esophageal cancer after MIE compared to OE. SUMMARY BACKGROUND DATA: MIE is becoming an increasingly common approach in the surgical treatment of esophageal cancer. A recent meta-analysis suggested 18% lower 5-year all-cause mortality after MIE compared to OE, but the quality of the included studies was limited. METHODS: Population-based cohort study including almost all patients who underwent elective esophagectomy for esophageal cancer in Sweden or Finland in 2010 to 2016, with follow-up until end of 2019. Cox regression was used to provide hazard ratios (HRs) with 95% confidence intervals (CIs) of all-cause 5-year mortality (main outcome) after MIE (hybrid or total) versus OE. Adjustments were made for age, sex, comorbidity, pathological tumor stage, histological tumor type, neoadjuvant chemo(radio)therapy, country, and annual hospital volume of esophagectomy. RESULTS: Among all 1264 patients, 470 (37.2%) underwent MIE and 794 (62.8%) underwent OE. MIE was associated with an 18% decreased risk of all-cause 5-year mortality, compared to OE [adjusted HR 0.82, 95% CI 0.67- 1.00 ( P = 0.048)]. The HR of all-cause 5-year mortality was seemingly lower after total MIE compared to OE (adjusted HR 0.77, 95% CI 0.60-0.98) than after hybrid MIE compared to OE (adjusted HR 0.87, 95% CI 0.68-1.11). CONCLUSIONS: This bi-national study indicates that MIE is associated with a higher 5-year survival than OE in patients with esophageal cancer, and that the survival benefit is greater after total MIE than hybrid MIE.

An International Cohort Study of Prognosis Associated With Pathologically Complete Response Following Neoadjuvant Chemotherapy Versus Chemoradiotherapy of Surgical Treated Esophageal Adenocarcinoma.

OBJECTIVE: To compare overall (OS) and recurrence-free survival (RFS) in esophageal adenocarcinoma patients with a pathologically complete response (pCR) following neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). BACKGROUND: In the absence of survival differences in several prior studies comparing nCT with nCRT, the higher rate of pCR after nCRT has been suggested as reason to prefer this modality over nCT. METHODS: An international cohort study included data from 8 high-volume centers. Inclusion criteria was patients with esophageal adenocarcinoma, between 2008 and 2018, who had a pCR after nCT or nCRT. Univariate analysis was used to compare demographic factors, and Kaplan-Meier survival analysis used to compare 5-year OS and RFS between groups. RESULTS: In all, 465 patients with pCR following neoadjuvant treatment were included; 132 received nCT and 333 received nCRT. There was no statistically significant difference in 5-year OS between groups (78.8% (nCT) vs 65.5% (nCRT), P =0.099), with a similar result demonstrated in multivariate analysis (HR=1.19, 95% CI 0.77-1.84). 5-year RFS was significantly reduced in patients with a pCR following neoadjuvant chemoradiotherapy (75.3% (nCRT) vs 87.1% (nCT), P =0.026). Multivariate analysis confirmed nCRT was associated with a poorer 5-year RFS (HR=1.70, 95% CI 1.22-2.99). nCRT associated with a significantly greater prevalence of 5-year distant recurrence (odds ratio=2.50, 95% CI 1.25-4.99). CONCLUSIONS: The results of this international cohort study show that the prognosis of pCR following different neoadjuvant regimes differs, bringing into question the validity of this measure as an oncological surrogate when comparing neoadjuvant treatment schemes for esophageal adenocarcinoma.

Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study.

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ±â€Š0.02 and 0.82 ±â€Š0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Learning Curves of Ivor Lewis Totally Minimally Invasive Esophagectomy by Hospital and Surgeon Characteristics: A Retrospective Multinational Cohort Study.

OBJECTIVE: To describe the pooled learning curves of Ivor Lewis totally minimally invasive esophagectomy (TMIE) in hospitals stratified by predefined hospital- and surgeon-related factors. BACKGROUND: Ivor Lewis (TMIE is known to have a long learning curve which is associated with considerable learning associated morbidity. It is unknown whether hospital and surgeon characteristics are associated with more efficient learning. METHODS: A retrospective analysis of prospectively collected data of consecutive Ivor Lewis TMIE patients in 14 European hospitals was performed. Outcome parameters used as proxy for efficient learning were learning curve length, learning associated morbidity, and the plateau level regarding anastomotic leakage and textbook outcome. Pooled incidences were plotted for the factor-based subgroups using generalized additive models and 2-phase models. Casemix predicted outcomes were plotted and compared with observed outcomes. The investigated factors included annual volume, TMIE experience, clinic visits, courses and fellowships followed, and proctor supervision. RESULTS: This study included 2121 patients. The length of the learning curve was shorter for centers with an annual volume >50 compared to centers with an annual volume <50. Analysis with an annual volume cut-off of 30 cases showed similar but less pronounced results. No outcomes suggesting more efficient learning were found for longer experience as consultant, visiting an expert clinic, completing a minimally invasive esophagectomy fellowship or implementation under proctor supervision. CONCLUSIONS: More efficient learning was observed in centers with higher annual volume. Visiting an expert clinic, completing a fellowship, or implementation under a proctor's supervision were not associated with more efficient learning.

Cancer-Related Fatigue After Esophageal Cancer Surgery: Impact of Postoperative Complications.

BACKGROUND: The impact of postoperative complications on cancer-related fatigue is unknown. This nationwide prospective cohort study aimed to assess the trajectory of cancer-related fatigue and the influence of predefined postoperative complications on cancer-related fatigue up to 2 years after esophageal cancer surgery. METHODS: The patients in this study underwent esophagectomy between 2013 and 2019 in Sweden. The exposure was predefined postoperative complications. The outcome was cancer-related fatigue measured by the fatigue scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the EORTC QLQ-Fatigue 12 (QLQ-FA12) questionnaire. Linear mixed-effects models provided adjusted fatigue scores and mean score differences (MDs) with 95% confidence intervals (CIs) between patients with and without predefined complications. RESULTS: The study enrolled 331 patients. The QLQ-C30 fatigue score increased with clinical relevance among patients with any complications (MD, 5.8; 95% CI, 2.6-9.0) who had a higher Clavien-Dindo classification (grades 2 to 3a: MD, 7.3; 95% CI, 3.1-11.5), a medical complication (MD, 6.9; 95% CI, 3.0-10.7), or a pulmonary complication (MD, 6.9; 95% CI, 2.1-11.6) for 1-1.5 years and remained stable until 2 years after esophagectomy. Similar patterns were found in the QLQ-FA12 fatigue and QLQ-FA12 physical and emotional subscales, but not in the cognitive subscales. CONCLUSIONS: Complications in general and medical and pulmonary complications in particular might be associated with increased cancer-related fatigue after esophagectomy.