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Item does not contain fulltext, OBJECTIVE: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer. SUMMARY OF BACKGROUND DATA: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer. METHODS: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods. RESULTS: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% ( P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P <0.001), median lymph node harvest increased from 15 to 19 ( P <0.001), and median survival increased from 35 to 41 months ( P = 0.027). CONCLUSION: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Item does not contain fulltext, OBJECTIVE: To evaluate the learning curve of laparoscopic gastrectomy (LG) after an implementation program. BACKGROUND: Although LG is increasingly being performed worldwide, little is known about the learning curve. METHODS: Consecutive patients who underwent elective LG for gastric adenocarcinoma with curative intent in each of the 5 highest-volume centers in the Netherlands were enrolled. Generalized additive models and a 2-piece model with a break point were used to determine the learning curve length. Analyses were corrected for casemix and were performed for LG and for the subgroups distal gastrectomy (LDG) and total gastrectomy (LTG). The learning curve effect was assessed for (1) anastomotic leakage; and (2) the occurrence of postoperative complications, conversions to open surgery, and short-term oncological parameters. RESULTS: In total 540 patients were included for analysis, 108 patients from each center; 268 patients underwent LDG and 272 underwent LTG. First, for LG, no learning effect regarding anastomotic leakage could be identified: the rate of anastomotic leakage initially increased, then reached a plateau after 36 cases at 10% anastomotic leakage. Second, the level of overall complications reached a plateau after 20 cases, at 38% overall complications, and at 5% conversions. For both LDG and LTG, each considered separately, fluctuations in secondary outcomes and anastomotic leakage followed fluctuations in casemix. CONCLUSION: On the basis of our study of the first 108 procedures of LG in 5 high-volume centers with well-trained surgeons, no learning curve effect could be identified regarding anastomotic leakage. A learning curve effect was found with respect to overall complications and conversion rate.

Item does not contain fulltext, Conflicting results are reported on the association between post-esophagectomy complications and long-term survival. This multicenter study assesses the association between complications after an esophagectomy and long-term overall survival. Five Dutch high-volume centers collected data from consecutive patients undergoing esophagectomy between 2010 and 2016 and merged these with long-term survival data from the Netherlands Cancer Registry. Exclusion criteria were non-curative resections and 90-day mortality, among others. Primary outcome was overall survival related to the presence of a postoperative complication in general. Secondary outcomes analyzed the presence of anastomotic leakage and cardiopulmonary complications. Propensity score matching was performed and the outcomes were analyzed via Log-Rank test and Kaplan Meier analysis. Among the 1225 patients included, a complicated course occurred in 719 patients (59.0%). After matching for baseline characteristics, 455 pairs were successfully balanced. Patients with an uncomplicated postoperative course had a 5-year overall survival of 51.7% versus 44.4% in patients with complications (P = 0.011). Anastomotic leakage occurred in 18.4% (n = 226), and in 208 matched pairs, it was shown that the 5-year overall survival was 57.2% in patients without anastomotic leakage versus 44.0% in patients with anastomotic leakage (P = 0.005). Overall cardiopulmonary complication rate was 37.1% (n = 454), and in 363 matched pairs, the 5-year overall survival was 52.1% in patients without cardiopulmonary complications versus 45.3% in patients with cardiopulmonary complications (P = 0.019). Overall postoperative complication rate, anastomotic leakage, and cardiopulmonary complications were associated with a decreased long-term survival after an esophagectomy. Efforts to reduce complications might further improve the overall survival for patients treated for esophageal carcinoma.

Item does not contain fulltext, INTRODUCTION: Failure to rescue (FTR) is an important outcome measure after esophagectomy and reflects mortality after postoperative complications. Differences in FTR have been associated with hospital resection volume. However, insight into how centers manage complications and achieve their outcomes is lacking. Anastomotic leak (AL) is a main contributor to FTR. This study aimed to assess differences in FTR after AL between centers, and to identify factors that explain these differences. METHODS: TENTACLE - Esophagus is a multicenter, retrospective cohort study, which included 1509 patients with AL after esophagectomy. Differences in FTR were assessed between low-volume (<20 resections), middle-volume (20-60 resections) and high-volume centers (≥60 resections). Mediation analysis was performed using logistic regression, including possible mediators for FTR: case-mix, hospital resources, leak severity and treatment. RESULTS: FTR after AL was 11.7%. After adjustment for confounders, FTR was lower in high-volume vs. low-volume (OR 0.44, 95%CI 0.2-0.8), but not versus middle-volume centers (OR 0.67, 95%CI 0.5-1.0). After mediation analysis, differences in FTR were found to be explained by lower leak severity, lower secondary ICU readmission rate and higher availability of therapeutic modalities in high-volume centers. No statistically significant direct effect of hospital volume was found: high-volume vs. low-volume 0.86 (95%CI 0.4-1.7), high-volume vs. middle-volume OR 0.86 (95%CI 0.5-1.4). CONCLUSION: Lower FTR in high-volume compared with low-volume centers was explained by lower leak severity, less secondary ICU readmissions and higher availability of therapeutic modalities. To reduce FTR after AL, future studies should investigate effective strategies to reduce leak severity and prevent secondary ICU readmission.

Contains fulltext : 294540.pdf (Publisher’s version ) (Open Access), 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 tre

Contains fulltext : 294526.pdf (Publisher’s version ) (Closed access), It is unknown whether Ivor Lewis (IL) or McKeown (McK) esophagectomy is preferred in patients with potentially curable esophageal or gastro-esophageal junction (GEJ) cancer. Patients with mid- and distal esophageal and GEJ cancer without distant metastases who underwent IL or McK esophagectomy in the Netherlands between 2015 and 2017, were selected from the Netherlands Cancer Registry. Patients were propensity score matched for sex, age, American Society of Anesthesiologist classification, comorbidity, tumor type, tumor location, clinical stage, neoadjuvant treatment and year of diagnosis. The primary outcome was a 3-year relative survival (RS). Secondary outcome parameters were number of lymph nodes examined, number of positive lymph nodes, radical resection rate, tumor regression grade, post-operative complications and mortality. A total of 1627 patients who underwent IL (n = 1094) or McK (n = 533) esophagectomy were included. Patient and tumor characteristics were balanced after propensity score matching, leaving 658 patients to be compared. The 3-year RS was 54% after IL and 50% after McK esophagectomy, P = 0.140. The median number of lymph nodes examined, median number of positive lymph nodes, radical resection rate and tumor regression grade were comparable between both groups. Recurrent laryngeal nerve palsy (2 vs. 5%, P = 0.006) occurred less frequently after IL esophagectomy. No differences were observed in post-operative anastomotic leakage rate, pulmonary complication rate and mortality rates. There was no statistically significant difference in the 3-year RS between IL and McK esophagectomy. Based on these results, both IL and McK esophagectomy can be performed in patients with mid to distal esophageal and GEJ cancer.

Item does not contain fulltext, BACKGROUND: The COVID-19 pandemic has affected the entire global healthcare system, including oncological care. This study investigated the effects of the COVID-19 pandemic on the diagnosis, stage, and treatment of esophagogastric cancer in the Netherlands. METHODS: Patients diagnosed in 2020 were divided into 5 periods, based on the severity of the COVID-19 pandemic in the Netherlands, and compared to patients diagnosed in the same period in the years 2017-2019. Patient characteristics and treatments were evaluated for esophageal cancer (EC) and gastric cancer (GC) separately. RESULTS: The number of esophagogastric cancer diagnoses decreased prominently during the first 2 months of the COVID-19 pandemic. During this period, a significantly higher percentage of GC patients was diagnosed with incurable disease (52.5% in 2017-2019 and 67.7% in 2020, p = 0.011). We observed a significant reduction in the percentage of patients with potentially curable EC treated with resection and neoadjuvant chemoradiotherapy (from 35.0% in 2017-2019 to 27.3% in 2020, p < 0.001). Also, patients diagnosed with incurable GC were treated less frequently with a resection (from 4.6% in 2017-2019 to 1.5% in 2020, p = 0.009) in the second half of 2020. CONCLUSIONS: Compared to previous years, the number of esophagogastric cancer diagnoses decreased in the first 2 months of the COVID-19 pandemic, while an increased percentage of patients was diagnosed with incurable disease. Both in the curative and palliative setting, patients were less likely to be treated with a surgical resection.

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Contains fulltext : 282376.pdf (Publisher’s version ) (Open Access), BACKGROUND: Anastomotic leak (AL) is a common but severe complication after oesophagectomy. It is unknown how to determine the severity of AL objectively at diagnosis. Determining leak severity may guide treatment decisions and improve future research. This study aimed to identify leak-related prognostic factors for mortality, and to develop a Severity of oEsophageal Anastomotic Leak (SEAL) score. METHODS: This international, retrospective cohort study in 71 centres worldwide included patients with AL after oesophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. Leak-related prognostic factors were identified after adjusting for confounders and were included in multivariable logistic regression to develop the SEAL score. Four classes of leak severity (mild, moderate, severe, and critical) were defined based on the risk of 90-day mortality, and the score was validated internally. RESULTS: Some 1509 patients with AL were included and the 90-day mortality rate was 11.7 per cent. Twelve leak-related prognostic factors were included in the SEAL score. The score showed good calibration and discrimination (c-index 0.77, 95 per cent c.i. 0.73 to 0.81). Higher classes of leak severity graded by the SEAL score were associated with a significant increase in duration of ICU stay, healing time, Comprehensive Complication Index score, and Esophagectomy Complications Consensus Group classification. CONCLUSION: The SEAL score grades leak severity into four classes by combining 12 leak-related predictors and can be used to the assess severity of AL after oesophagectomy.

Contains fulltext : 251521.pdf (Publisher’s version ) (Open Access), BACKGROUND: Minimally invasive esophagectomy (MIE) is a complex and technically demanding procedure with a long learning curve, which is associated with increased morbidity and mortality. To master MIE, training in essential steps is crucial. Yet, no consensus on essential steps of MIE is available. The aim of this study was to achieve expert consensus on essential steps in Ivor Lewis and McKeown MIE through Delphi methodology. METHODS: Based on expert opinion and peer-reviewed literature, essential steps were defined for Ivor Lewis (IL) and McKeown (McK) MIE. In a round table discussion, experts finalized the lists of steps and an online Delphi questionnaire was sent to an international expert panel (7 European countries) of minimally invasive upper GI surgeons. Based on replies and comments, steps were adjusted and rephrased and sent in iterative fashion until consensus was achieved. RESULTS: Two Delphi rounds were conducted and response rates were 74% (23 out of 31 experts) for the first and 81% (27 out of 33 experts) for the second round. Consensus was achieved on 106 essential steps for both the IL and McK approach. Cronbach's alpha in the first round was 0.78 (IL) and 0.78 (McK) and in the second round 0.92 (IL) and 0.88 (McK). CONCLUSIONS: Consensus among European experts was achieved on essential surgical steps for both Ivor Lewis and McKeown minimally invasive esophagectomy.

Contains fulltext : 283432.pdf (Publisher’s version ) (Open Access), OBJECTIVE: Biological sex differences in cancer are increasingly acknowledged. Here, we examined these differences in clinicopathological characteristics and survival in microsatellite instability (MSI)-high and microsatellite stable (MSS) gastric cancer (GC). DESIGN: We analysed MSI status by polymerase chain reaction (PCR) and/or mismatch repair (MMR) status by immunohistochemistry in a pooled analysis of individual patient data from one retrospective cohort from Cologne, and the randomised phase III clinical trials D1/D2 and CRITICS. All patients had resectable adenocarcinoma of the stomach and/or gastro-oesophageal junction. Patients were treated with either surgery only or perioperative chemo(radio)therapy. RESULTS: MSI and/or MMR analyses on 1307 tumours resulted in 1192 (91.2%) MSS and/or MMR proficient (MMRP) [median age, 65 years; 759 males (63.7%); 619 treated with surgery only (51.9%)], and 115 (8.8%) MSI-high [median age, 69 years; 67 males (58.3%); 76 treated with surgery only (66.1%)] GC cases. Males had shorter overall survival (OS) than female MSI-high GC (5-year OS 34.7% vs. 69.7%; hazard ratio (HR) 2.68, 95%CI 1.60 to 4.49; p < 0.001). Females with MSI-high had longer OS than those with MSS/MMRP GC (HR 0.61, 95%CI 0.41 to 0.92; p = 0.02). Males with MSI-high did not have longer OS than those with MSS/MMRP GC (HR 1.26, 95%CI 0.94 to 1.69; p = 0.12). CONCLUSIONS: MSI-high GC males had a significantly worse prognosis compared to their female counterparts in three independent cohorts. In addition, the favourable prognostic value of MSI was only seen in females and not in males. These observations emphasise the need to consider sex differences in prognosis and treatment effects in oncology. CLINICAL TRIAL REGISTRATION: The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02.

Item does not contain fulltext, BACKGROUND: In recent years, minimally invasive Ivor Lewis (IL) esophagectomy with high intrathoracic anastomosis has emerged as surgical standard of care for esophageal cancer in expert centers. Alongside this process, many divergent technical aspects of this procedure have been devised in different centers. This study aims at achieving international consensus on the surgical steps of IL reconstruction using Delphi methodology. METHODS: The expert panel consisted of specialized esophageal surgeons from 8 European countries. During a two-round Delphi process, a detailed analysis and consensus on key steps of intrathoracic gastric tube reconstruction (IL esophagectomy) was performed. RESULTS: Response rates in Delphi rounds 1 and 2 were 100% (22 of 22 experts) and 83.3% (20 of 24 experts), respectively. Three essential technical areas of intrathoracic gastric tube reconstruction were identified: first, vascularization of the gastric conduit, second, gastric mobilization, tube formation and pull-up, and third, anastomotic technique. In addition, 3 main techniques for minimally invasive intrathoracic anastomosis are currently practiced: (i) end-to-side circular stapled, (ii) end-to-side double stapling, and (iii) side-to-side linear stapled technique. The step-by-step procedural analysis unveiled common approaches but also different expert practice. CONCLUSION: This precise technical description may serve as a clinical guideline for intrathoracic reconstruction after esophagectomy. In addition, the results may aid to harmonize the technical evolution of this complex surgical procedure and thereby facilitate surgical training.

Item does not contain fulltext, IMPORTANCE: The optimal staging for gastric cancer remains a matter of debate. OBJECTIVE: To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. EXPOSURES: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. RESULTS: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. CONCLUSIONS AND RELEVANCE: This study's findings suggest an apparently limi

Contains fulltext : 239058.pdf (Publisher’s version ) (Open Access), INTRODUCTION: The value of routine intensive care unit (ICU) admission after minimally invasive esophagectomy (MIE) has been questioned. This study aimed to investigate Dutch hospital variation regarding length of direct postoperative ICU stay, and the impact of this hospital variation on short-term surgical outcomes. MATERIALS AND METHODS: Patients registered in the Dutch Upper Gastrointestinal Cancer Audit (DUCA) undergoing curative MIE were included. Length of direct postoperative ICU stay was dichotomized around the national median into short ICU stay ( ≤ 1 day) and long ICU stay ( > 1 day). A case-mix corrected funnel plot based on multivariable logistic regression analyses investigated hospital variation. The impact of this hospital variation on short-term surgical outcomes was investigated using multilevel multivariable logistic regression analyses. RESULTS: Between 2017 and 2019, 2110 patients from 16 hospitals were included. Median length of postoperative ICU stay was 1 day [hospital variation: 0-4]. The percentage of short ICU stay ranged from 0 to 91% among hospitals. Corrected for case-mix, 7 hospitals had statistically significantly higher short ICU stay rates and 6 hospitals had lower rates. ICU readmission, in-hospital/30-day mortality, failure to rescue, postoperative pneumonia, cardiac complications and anastomotic leakage were not associated with hospital variation in length of ICU stay. Total length of hospital stay was significantly shorter in hospitals with relatively short ICU stay. CONCLUSION: This study showed significant hospital variation in postoperative length of ICU stay after MIE. Short ICU stay was associated with shorter overall hospital admission and did not negatively impact short-term surgical outcomes. More selected use of ICU resources could result in a national significant cost reduction.

Contains fulltext : 239057.pdf (Publisher’s version ) (Open Access), BACKGROUND: Esophagectomy has major effects on health-related quality of life (HR-QoL). Postoperative complications might contribute to a decreased HR-QOL. This population-based study aimed to investigate the difference in HR-QoL between patients with and without complications after esophagectomy for cancer. METHODS: A prospective comparative cohort study was performed with data from the Netherlands Cancer Registry (NCR) and Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP). All patients with esophageal and gastroesophageal junction (GEJ) cancer after esophagectomy in the period 2015-2018 were enrolled. The study investigated HR-QoL at baseline, then 3, 6, 9, 12, 18, and 24 months postoperatively, comparing patients with and without complications as well as with and without anastomotic leakage. RESULTS: The 486 enrolled patients comprised 270 patients with complications and 216 patients without complications. Significantly more patients with complications had comorbidities (69.6% vs 57.3%; p = 0.001). No significant difference in HR-QoL was found over time between the patients with and without complications. In both groups, a significant decline in short-term HR-QoL was found in various HR-QoL domains, which were restored to the baseline level during the 12-month follow-up period. No significant difference was found in HR-QoL between the patients with and without anastomotic leakage. The patients with grades 2 and 3 anastomotic leakage reported significantly more "choking when swallowing" at 6 months (ß = 14.5; 95% confidence interval [CI], - 24.833 to - 4.202; p = 0.049), 9 months (ß = 22.4, 95% CI, - 34.259 to - 10.591; p = 0.007), and 24 months (ß = 24.6; 95% CI, - 39.494 to - 9.727; p = 0.007) than the patients with grade 1 or no anastomotic leakage. CONCLUSION: In general, postoperative complications were not associated with decreased short- or long-term HR-QoL for patients after esophagectomy for esophageal or GEJ cancer. The

Item does not contain fulltext, OBJECTIVE: In the pursuit of quality improvement, this study aimed to investigate volume-outcome trends in oncologic esophagectomy in the Netherlands. SUMMARY OF BACKGROUND DATA: Concentration of Dutch esophageal cancer care was dictated by introducing an institutional minimum of 20 resections/yr. METHODS: This nationwide cohort study included all esophagectomy patients registered in the Dutch Upper Gastrointestinal Cancer Audit in 2016-2019 from hospitals currently still performing esophagectomies. Annual esophagectomy hospital volume was assigned to each patient and categorized into quartiles. Multivariable logistic regression investigated short-term surgical outcomes. Restricted cubic splines investigated if volume-outcome relationships eventually plateaued. RESULTS: In 16 hospitals, 3135 esophagectomies were performed. First volume quartile hospitals performed 24-39 resections/yr; second, third, and fourth quartile hospitals performed 40-53, 54-69, and 70-101, respectively. Compared to quartile 1, in quartiles 2 to 4, overall/severe/technical complication, anastomotic leakage, and prolonged hospital/intensive care unit stay rates were significantly lower and textbook outcome and lymph node yield were higher. When raising the cut-off from the first to second quartile, higher-volume centers had less technical complications [Adjusted odds ratio (aOR): 0.82, 95% confidence interval (CI): 0.70-0.96], less anastomotic leakage (aOR: 0.80, 95% CI: 0.66-0.97), more textbook outcome (aOR: 1.25, 95% CI: 1.07-1.46), shorter intensive care unit stay (aOR: 0.80, 95% CI: 0.69-0.93), and higher lymph node yield (aOR: 3.56, 95% CI: 2.68-4.77). For most outcomes the volume-outcome trend plateaued at 50-60 annual resections, but lymph node yield and anastomotic leakage continued to improve. CONCLUSION: Although this study does not reflect on individual hospital quality, there appears to be a volume trend towards better outcomes in high-volume centers. Projects have been initiated

Item does not contain fulltext, BACKGROUND: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE. OBJECTIVE: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. INTERVENTION: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. MAIN OUTCOMES AND MEASURES: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. RESULTS: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI,

Contains fulltext : 239053.pdf (Publisher’s version ) (Open Access), BACKGROUND: Anastomotic leakage has a great impact on clinical outcomes after esophagectomy. It has never been studied whether anastomotic leakage is of equal severity between different types of esophagectomy (i.e., transhiatal, McKeown and Ivor Lewis) in terms of postoperative mortality and morbidity. METHODS: All esophageal cancer patients with anastomotic leakage after transhiatal, McKeown or Ivor Lewis esophagectomy between 2011 and 2019 were selected from the Dutch Upper Gastrointestinal Cancer Audit (DUCA) registry. The primary outcome was 30-day/in-hospital mortality. Secondary outcomes included postoperative complications, re-operation and ICU readmission rate. RESULTS: Data from 1030 patients with anastomotic leakage after transhiatal (n=287), McKeown (n=397) and Ivor Lewis esophagectomy (n=346) were evaluated. The 30-day/in-hospital mortality rate was 4.5% in patients with leakage after transhiatal esophagectomy, 8.1% after McKeown and 8.1% after Ivor Lewis esophagectomy (P=0.139). After correction for confounders, leakage after transhiatal resection was associated with lower mortality (OR 0.152-0.699, P=0.004), but mortality after McKeown and Ivor Lewis esophagectomy was similar. Re-operation rate was 24.0% after transhiatal, 40.6% after McKeown and 41.3% after Ivor Lewis esophagectomy (P<0.001). ICU readmission rate was 24.0% after transhiatal, 37.8% after McKeown and 43.4% after Ivor Lewis esophagectomy (P<0.001). CONCLUSION: This study in patients with anastomotic leakage confirms a strong association between severity of clinical consequences and different types of esophagectomy. It supports the hypothesis that cervical leakage is generally less severe than intrathoracic leakage. The clinical impact of anastomotic leakage should be taken into account, in addition to its incidence, when different types of esophagectomy are compared by clinicians or researchers.

Contains fulltext : 218586.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 225948.pdf (Publisher’s version ) (Open Access), Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.

Contains fulltext : 215779.pdf (publisher's version ) (Open Access), BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored

Contains fulltext : 206269.pdf (publisher's version ) (Open Access)

Contains fulltext : 203355.pdf (publisher's version ) (Closed access), OBJECTIVE: To investigate the morbidity that is associated with the learning curve of minimally invasive esophagectomy. BACKGROUND: Although learning curves have been described, it is currently unknown how much extra morbidity is associated with the learning curve of technically challenging surgical procedures. METHODS: Prospectively collected data were retrospectively analyzed of all consecutive patients undergoing minimally invasive Ivor Lewis esophagectomy in 4 European expert centers. The primary outcome parameter was anastomotic leakage. Secondary outcome parameters were operative time and textbook outcome ("optimal outcome"). Learning curves were plotted using weighted moving average and CUSUM analysis was used to determine after how many cases the plateau was reached. Learning associated morbidity was calculated with area under the curve analysis. RESULTS: This study included 646 patients. Three of the 4 hospitals reached the plateau of 8% anastomotic leakage. The length of the learning curve was 119 cases. The mean incidence of anastomotic leakage decreased from 18.8% during the learning phase to 4.5% after the plateau had been reached (P < 0.001). Thirty-six extra patients (10.1% of all patients operated on during the learning curve) experienced learning associated anastomotic leakage, that could have been avoided if patients were operated by surgeons who had completed the learning curve. The incidence of textbook outcome increased from 28% to 53% and the mean operative time decreased from 344 minutes to 270 minutes. CONCLUSIONS: A considerable number of 36 extra patients (10.1%) experienced learning associated anastomotic leakage. More research is urgently needed to investigate how learning associated morbidity can be reduced to increase patient safety during learning curves.

Contains fulltext : 200332.pdf (publisher's version ) (Open Access), BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and (18)F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSIO

Contains fulltext : 193307.pdf (publisher's version ) (Closed access), INTRODUCTION: The optimal time between end of neoadjuvant chemoradiotherapy (nCRT) and oesophagectomy is unknown. The aim of this study was to assess the association between this interval and pathologic complete response rate (pCR), morbidity and 30-day/in-hospital mortality. METHODS: Patients with oesophageal cancer treated with nCRT and surgery between 2011 and 2016 were selected from a national database: the Dutch Upper Gastrointestinal Cancer Audit (DUCA). The interval between end of nCRT and surgery was divided into six periods: 0-5 weeks (n = 157;A), 6-7 weeks (n = 878;B), 8-9 weeks (n = 972;C), 10-12 weeks (n = 720;D), 13-14 weeks (n = 195;E) and 15 or more weeks (n = 180;F). The association between these interval groups and outcomes was investigated using univariable and multivariable analysis with group C (8-9 weeks) as reference. RESULTS: In total, 3102 patients were included. The pCR rate for the groups A to F was 31%, 28%, 26%, 31%, 40% and 37%, respectively. A longer interval was associated with a higher probability of pCR (>/=10 weeks for adenocarcinoma: odds ratio [95% confidence interval]: 1.35 [1.00-1.83], 1.95 [1.24-3.07], 1.64 [0.99-2.71] and >/=13 weeks for squamous cell carcinoma: 2.86 [1.23-6.65], 2.67 [1.29-5.55]. Patients operated >/=10 weeks after nCRT had the same probability for intraoperative/postoperative complications. Patients from groups D and F had a higher 30-day/in-hospital mortality (1.80 [1.08-3.00], 3.19 [1.66-6.14]). CONCLUSION: An interval of >/=10 weeks for adenocarcinoma and >/=13 weeks for squamous cell carcinoma between nCRT and oesophagectomy was associated with a higher probability of having a pCR. Longer intervals were not associated with intraoperative/postoperative complications. The 30-day/in-hospital mortality was higher in patients with extended intervals (10-12 and >/=15 weeks); however, this might have been due to residual confounding.

Item does not contain fulltext, BACKGROUND: Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma. METHODS: In this investigator-initiated, open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who had stage IB- IVA resectable gastric or gastro-oesophageal adenocarcinoma (as defined by the American Joint Committee on Cancer, sixth edition), with a WHO performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and kidney function. Patients were enrolled from 56 hospitals in the Netherlands, Sweden, and Denmark, and were randomly assigned (1:1) with a computerised minimisation programme with a random element to either perioperative chemotherapy (chemotherapy group) or preoperative chemotherapy with postoperative chemoradiotherapy (chemoradiotherapy group). Randomisation was done before patients were given any preoperative chemotherapy treatment and was stratified by histological subtype, tumour localisation, and hospital. Patients and investigators were not masked to treatment allocation. Surgery consisted of a radical resection of the primary tumour and at least a D1+ lymph node dissection. Postoperative treatment started within 4-12 weeks after surgery. Chemotherapy consisted of three preoperative 21-day cycles and three postoperative cycles of intravenous epirubicin (50 mg/m(2) on day 1), cisplatin (60 mg/m(2) on day 1) or oxaliplatin (130 mg/m(2) on day 1), and capecitabine (1000 mg/m(2) orally as tablets twice daily for 14 days in combination with epirubicin and cisplatin, or 625 mg/m(2) orally as tablets twice daily for 21 days in combination with epirubicin and oxaliplatin), received onc

Contains fulltext : 183843.pdf (publisher's version ) (Closed access)

Contains fulltext : 196889.pdf (publisher's version ) (Open Access), BACKGROUND: Although radical surgery remains the cornerstone of cure in resectable gastric cancer, survival remains poor. Current evidence-based (neo)adjuvant strategies have shown to improve outcome, including perioperative chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy. However, these regimens suffer from poor patient compliance, particularly in the postoperative phase of treatment. The CRITICS-II trial aims to optimize preoperative treatment by comparing three treatment regimens: (1) chemotherapy, (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy. METHODS: In this multicentre phase II non-comparative study, patients with clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2) 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event-free survival, 1 year after randomisation (events are local and/or regional recurrence or progression, distant recurrence, or death from any cause). Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers. DISCUSSION: The aim of this study is to select the most promising among three preoperative treatment arms in patients with resectable gastric adenocarcinoma. This treatment regimen will subsequently be compared with the standard therapy in a phase III trial. TRIAL REGISTRATION: clinicaltrials.gov NCT02931890 ; registered 13 October 2016. Date of first enrolment: 21 December 2017.

Item does not contain fulltext, BACKGROUND: In order to determine the optimal combination of perioperative chemotherapy and chemoradiotherapy for Western patients with advanced resectable gastric cancer, the international multicentre CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated. In this trial, patients with resectable gastric cancer were randomised before start of treatment between adjuvant chemotherapy or adjuvant chemoradiotherapy following neoadjuvant chemotherapy plus gastric cancer resection. The purpose of this study was to report on surgical morbidity and mortality in this trial, and to identify factors associated with surgical morbidity. METHODS: Patients who underwent a gastrectomy with curative intent were selected. Logistic regression analyses were used to assess risk factors for developing postoperative complications. RESULTS: Between 2007 and 2015, 788 patients were included in the CRITICS trial, of whom 636 patients were eligible for current analyses. Complications occurred in 296 patients (47%). Postoperative mortality was 2.2% (n = 14). Complications due to anastomotic leakage was cause of death in 5 patients. Failure to complete preoperative chemotherapy (OR = 2.09, P = 0.004), splenectomy (OR = 2.82, P = 0.012), and male sex (OR = 1.55, P = 0.020) were associated with a greater risk for postoperative complications. Total gastrectomy and oesophago-cardia resection were associated with greater risk for morbidity compared with subtotal gastrectomy (OR = 1.88, P = 0.001 and OR = 1.89, P = 0.038). CONCLUSION: Compared to other Western studies, surgical morbidity in the CRITICS trial was slightly higher whereas mortality was low. Complications following anastomotic leakage was the most important factor for postoperative mortality. Important proxies for developing postoperative complications were failure to complete preoperative chemotherapy, splenectomy, male sex, total gastrectomy, and oesophago-cardia resection.

Item does not contain fulltext, OBJECTIVE: The purpose of this study was to evaluate surgicopathological quality and protocol adherence for lymphadenectomy in the CRITICS trial. SUMMARY OF BACKGROUND DATA: Surgical quality assurance is a key element in multimodal studies for gastric cancer. In the multicenter CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients with resectable gastric cancer were randomized for preoperative chemotherapy, followed by gastrectomy with a D1+ lymphadenectomy (removal of stations 1 to 9 and 11), followed by either chemotherapy or chemoradiotherapy. METHODS: Surgicopathological compliance was defined as removal of >/=15 lymph nodes. Surgical compliance was defined as removal of the indicated lymph node stations. Surgical contamination was defined as removal of lymph node stations that should be left in situ. The Maruyama Index (MI, lower is better), which has proven to be an indicator of surgical quality and is strongly associated with survival, was analyzed. RESULTS: Between 2007 and 2015, 788 patients were randomized, of whom 636 patients underwent a gastrectomy with curative intent. Surgicopathological compliance occurred in 72.8% (n = 460) of the patients and improved from 55.0% (2007) to 90.0% (2015). Surgical compliance occurred in 41.1% (n = 256). Surgical contamination occurred in 59.6% (n = 371). Median MI was 1 (range 0 to 136). CONCLUSION: Surgical quality in the CRITICS trial was excellent, with a MI of 1. Surgicopathological compliance improved over the years. This might be explained by the quality assurance program within the study and centralization of gastric cancer surgery in the Netherlands.

Contains fulltext : 190017.pdf (publisher's version ) (Closed access)

Item does not contain fulltext, BACKGROUND: Studies investigating the association between hospital volume and quality of gastric cancer surgery are lacking. In the present study, the effect of hospital volume on quality of gastric cancer surgery was evaluated by analysing data from the CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial. METHODS: Patients who underwent gastrectomy with curative intent in the Netherlands were selected from the CRITICS trial database. Annual hospital volume of participating centres was derived from the Netherlands Cancer Registry. Hospital volume was categorized into very low (1-10 gastrectomies per year per institution), low (11-20), medium (21-30) and high (31 or more), and linked to the CRITICS database. Quality of surgery was analysed by surgicopathological compliance (removal of at least 15 lymph nodes), surgical compliance (removal of indicated lymph node stations) and the Maruyama Index. Postoperative morbidity and mortality were also compared between hospital categories. RESULTS: Between 2007 and 2015, 788 patients were included in the CRITICS study, of whom 494 were analysed. Surgicopathological compliance was higher (86.7 versus 50.4 per cent; P < 0.001), surgical compliance was greater (52.9 versus 19.8 per cent; P < 0.001) and median Maruyama Index was lower (0 versus 6; P = 0.006) in high-volume hospitals compared with very low-volume hospitals. There was no statistically significant difference in postoperative complications or mortality between the hospital volume categories. CONCLUSION: Surgery performed in high-volume hospitals was associated with better surgical quality than surgery carried out in lower-volume hospitals.

Contains fulltext : 190038.pdf (publisher's version ) (Open Access), Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients.Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future.Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing.Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this

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Contains fulltext : 193356.pdf (publisher's version ) (Open Access), BACKGROUND: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. METHODS: This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. DISCUSSION: In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of euro916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. TRIAL REGISTRATION: NCT03208621 . This trial was registered prospectively on June 30, 2017.

Contains fulltext : 199488.pdf (publisher's version ) (Closed access)

Contains fulltext : 177731.pdf (publisher's version ) (Closed access), BACKGROUND: Complex surgical procedures such as esophagectomy and gastrectomy for cancer are associated with substantial morbidity and mortality. The purpose of this study was to evaluate trends in postoperative morbidity, mortality, and associated failure-to-rescue (FTR), in patients who underwent a potentially curative resection for esophageal or gastric cancer in the Netherlands, and to investigate differences between the two groups. METHODS: All patients with esophageal or gastric cancer who underwent a potentially curative resection, registered in the Dutch Upper GI Cancer Audit (DUCA) between 2011 and 2014, were included. Primary outcomes were (major) postoperative complications, postoperative mortality and FTR. To investigate groups' effect on the outcomes of interest a mixed model was used. RESULTS: Overall, 2644 patients with esophageal cancer and 1584 patients with gastric cancer were included in this study. In patients with gastric cancer, postoperative mortality (7.7% in 2011 vs. 3.8% in 2014) and FTR (38% in 2011 and 19% in 2014) decreased significantly over the years. The adjusted risk of developing a major postoperative complication was lower (OR 0.54; 95% CI 0.42-0.70), but the risk of FTR was higher (OR 1.85; 95% CI 1.05-3.27) in patients with gastric cancer compared to patients with esophageal cancer. CONCLUSION: Once a postoperative complication occurred, patients with gastric cancer were more likely to die compared to patients with esophageal cancer. Underlying mechanisms like patient selection, and differences in structure and organization of care should be investigated. Next to morbidity and mortality, failure-to-rescue should be considered as an important outcome measure after esophagogastric cancer resections.

Contains fulltext : 175624.pdf (publisher's version ) (Closed access), OBJECTIVE: The aim of this study was to investigate 3-year survival following a randomized controlled trial comparing minimally invasive with open esophagectomy in patients with esophageal cancer. BACKGROUND: Research on minimally invasive esophagectomy (MIE) has shown faster postoperative recovery and a marked decrease in pulmonary complications. Debate is ongoing as to whether the procedure is equivalent to open resection regarding oncologic outcomes. The study is a follow-up study of the TIME-trial (traditional invasive vs minimally invasive esophagectomy, a multicenter, randomized trial). METHODS: Between June 2009 and March 2011, patients with a resectable intrathoracic esophageal carcinoma, including the gastroesophageal junction tumors (Siewert I), were randomized between open and MI esophagectomy with curative intent. Primary outcome was 3-year disease-free survival. Secondary outcomes include overall survival, lymph node yield, short-term morbidity, mortality, complications, radicality, local recurrence, and metastasis. Analysis was by intention-to-treat. This trial is registered with the Netherlands Trial Register, NTR TC 2452. Both trial protocol and short-term results have been published previously. RESULTS: One hundred fifteen patients were included from 5 European hospitals and randomly assigned to open (n = 56) or MI esophagectomy (n = 59). Combined overall 3-year survival was 40.4% (SD 7.7%) in the open group versus 50.5% (SD 8%) in the minimally invasive group (P = 0.207). The hazard ratio (HR) is 0.883 (0.540 to 1.441) for MIE compared with open surgery. Disease-free 3-year survival was 35.9% (SD 6.8%) in the open versus 40.2% (SD 6.9%) in the MI group [HR 0.691 (0.389 to 1.239). CONCLUSIONS: The study presented here depicted no differences in disease-free and overall 3-year survival for open and MI esophagectomy. These results, together with short-term results, further support the use of minimally invasive surgical techniques in the treatment of e

Contains fulltext : 174840.pdf (publisher's version ) (Closed access), BACKGROUND: Quality assurance is acknowledged as a crucial factor in the assessment of oncological surgical care. The aim of this study was to develop a composite measure of multiple outcome parameters defined as 'textbook outcome', to assess quality of care for patients undergoing oesophagogastric cancer surgery. METHODS: Patients with oesophagogastric cancer, operated on with the intent of curative resection between 2011 and 2014, were identified from a national database (Dutch Upper Gastrointestinal Cancer Audit). Textbook outcome was defined as the percentage of patients who underwent a complete tumour resection with at least 15 lymph nodes in the resected specimen and an uneventful postoperative course, without hospital readmission. Hospital variation in textbook outcome was analysed after adjustment for case-mix factors. RESULTS: In total, 2748 patients with oesophageal cancer and 1772 with gastric cancer were included in this study. A textbook outcome was achieved in 29.7 per cent of patients with oesophageal cancer and 32.1 per cent of those with gastric cancer. Adjusted textbook outcome rates varied from 8.5 to 52.4 per cent between hospitals. The outcome parameter 'at least 15 lymph nodes examined' had the greatest negative impact on a textbook outcome both for patients with oesophageal cancer and for those with gastric cancer. CONCLUSION: Most patients did not achieve a textbook outcome and there was wide variation between hospitals.

Contains fulltext : 177898.pdf (Publisher’s version ) (Open Access), BACKGROUND: The first and only randomized trial comparing open esophagectomy (OE) with minimally invasive esophagectomy (MIE) showed a significant lower incidence of post-operative respiratory infections in the patients who underwent MIE. In order to identify which specific factors are related to a better respiratory outcome in this trial an additional analysis was performed. METHODS: This was a prospective, multicenter, randomized controlled trial. Eligible patients, with a resectable intrathoracic esophageal carcinoma, including the gastro-esophageal (GE) junction tumors and Eastern Cooperative Oncology Group /=26 and OE were associated with a roughly threefold risk of developing a respiratory infection. CONCLUSIONS: Overweight patients and OE are independently associated with a significant higher incidence of post-operative respiratory infections, i.e., pneumonia.

Contains fulltext : 175660.pdf (publisher's version ) (Open Access), INTRODUCTION: Esophagectomy for cancer can be performed in a two-stage procedure with an intrathoracic anastomosis: the Ivor Lewis esophagectomy. A growing incidence of distal and gastroesophageal junction adenocarcinomas and increasing use of minimally invasive techniques have prompted interest in this procedure. The aim of this study was to assess short-term results of minimally invasive Ivor Lewis esophagectomy (MIE-IL). METHODS: A retrospective cohort study was performed from June 2007 until September 2014, including patients that underwent MIE-IL for distal esophageal and gastroesophageal junction cancer in six different hospitals in the Netherlands and Spain. Data were collected with regard to operative techniques, pathology and postoperative complications. RESULTS: In total, 282 patients underwent MIE-IL, of which 90.2 % received neoadjuvant therapy. Anastomotic leakage was observed in 43 patients (15.2 %), of whom 13 patients (4.6 %) had empyema, necessitating thoracotomy for decortication. With an aggressive treatment of complications, the 30-day and in-hospital mortality rate was 2.1 %. An R0-resection was obtained in 92.5 % of the patients. After neoadjuvant therapy, 20.1 % of patients had a complete response. CONCLUSIONS: Minimally invasive Ivor Lewis esophagectomy for distal esophageal and gastroesophageal junction adenocarcinomas is an upcoming approach for reducing morbidity caused by laparotomy and thoracotomy. Anastomotic leakage rate is still high possibly due to technical diversity of anastomotic techniques, and a high percentage of patients treated by neoadjuvant chemoradiotherapy. An aggressive approach to complications leads to a low mortality of 2.1 %. Further improvement and standardization in the anastomotic technique are needed in order to perform a safe intrathoracic anastomosis.

Contains fulltext : 172392.pdf (publisher's version ) (Closed access), BACKGROUND: In 2011, the Dutch Upper Gastrointestinal Cancer Audit (DUCA) group began nationwide registration of all patients undergoing surgery with the intention of resection for oesophageal or gastric cancer. The aim of this study was to describe the initiation and implementation of this process along with an overview of the results. METHODS: The DUCA is part of the Dutch Institute for Clinical Auditing. The audit provides (surgical) teams with reliable, weekly updated, benchmarked information on process and (case mix-adjusted) outcome measures. To accomplish this, a web-based registration was designed, based on a set of predefined quality measures. RESULTS: Between 2011 and 2014, a total of 2786 patients with oesophageal cancer and 1887 with gastric cancer were registered. Case ascertainment approached 100 per cent for patients registered in 2013. The percentage of patients with oesophageal cancer starting treatment within 5 weeks of diagnosis increased significantly over time from 32.5 per cent in 2011 to 41.0 per cent in 2014 (P < 0.001). The percentage of patients with a minimum of 15 examined lymph nodes in the resected specimen also increased significantly for both oesophageal cancer (from 50.3 per cent in 2011 to 73.0 per cent in 2014; P < 0.001) and gastric cancer (from 47.5 per cent in 2011 to 73.6 per cent in 2014; P < 0.001). Postoperative mortality remained stable (around 4.0 per cent) for patients with oesophageal cancer, and decreased for patients with gastric cancer (from 8.0 per cent in 2011 to 4.0 per cent in 2014; P = 0.031). CONCLUSION: Nationwide implementation of the DUCA has been successful. The results indicate a positive trend for various process and outcome measures.

Item does not contain fulltext, BACKGROUND: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. METHODS: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41.4 Gy, given in 23 fractions of 1.8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. FINDINGS: Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171

Contains fulltext : 139017.pdf (publisher's version ) (Open Access), BACKGROUND: Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. METHODS: A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy\1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. RESULTS: 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade >/=3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity >/= grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. CONCLUSIONS: Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group.

1 november 2014, Item does not contain fulltext, OBJECTIVES: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. BACKGROUND: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. METHODS: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. RESULTS: One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). CONCLUSIONS: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Item does not contain fulltext, PURPOSE: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. METHODS AND MATERIALS: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m(2)) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. RESULTS: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. CONCLUSIONS: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.