Background and study aims:Active surveillance has been proposed for patients with esophageal cancer and a clinical complete response after neoadjuvant chemoradiotherapy (nCRT). This strategy involves repeated esophagogastroduodenoscopy (EGD) with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) to detect tumor regrowth or residual disease. The aim of this study was to assess safety of endoscopic procedures during active surveillance. Patients and methods:A prospective multicenter cohort including patients who were treated with nCRT for esophageal cancer and who underwent EGD with bite-on-bite biopsies and/or EUS (with fine-needle aspiration) was retrospectively analyzed. The primary outcome was the difference in number of serious adverse events (SAEs) in endoscopic procedures performed within vs. more than 3 months after nCRT. The secondary outcome was mechanical injury. Results:In 920 patients, 2291 endoscopic procedures were performed (57% EGD combined with EUS, 39% EGD only and 4% EUS only). Of these procedures, 819 (36%) were performed more than 3 months after nCRT in 186 patients. Two gastrointestinal bleedings were reported during endoscopic procedures performed within 3 months after nCRT. One gastrointestinal bleeding and two infections were reported after 3 months following nCRT. Frequency of SAEs before and after 3 months following completion of nCRT was not significantly different (2 vs. 3, odds ratio 2.7, 95% confidence interval 0.3-32.4, P = 0.36). Conclusions:EGD with bite-on-bite biopsies and EUS with FNA seem to be safe during an active surveillance strategy in esophageal cancer patients after nCRT.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's ' s neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (+/- 9). During median 59 months (p25-p75 - p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age < 71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039)

Although the risk of cancer progression in a Barrett’s esophagus (BE) is very low, worrying about cancer is known as an important factor affecting HRQoL. The aim of this study was to determine the proportion of BE patients with high levels of worry for cancer, to compare outcomes of patients endoscopically treated for BE neoplasia (DBE), non-dysplastic BE patients (NDBE) and patients with reflux symptoms, and to examine associated factors. We performed a cross sectional, exploratory, self-administered questionnaire study using the cancer worry scale, and the reflux disease questionnaire. A total of 192 DBE patients, 213 NDBE patients and 111 refractory reflux symptom patients were included from October 2019 until July 2021, 76.8% of BE participants were male and aged 66.9 years. High cancer worry was reported in 40.6% of the DBE patients and 36.2% of NDBE patient. Reflux patients scored statistically significant worse with 56.6% stated high cancer worry. Positive correlations were found between reflux symptoms and cancer worry in NDBE patients and reflux patients. In DBE patients’ negative correlations were found between higher cancer worry and younger age as well as a family history of esophageal carcinoma. A clinically significant group of BE patients reported high cancer worry, which was associated with reflux symptoms in NDBE patients and a younger age and a (family) history of esophageal carcinoma diagnosis in BE patients treated for (early) neoplasia. Physicians should communicate about the actual cancer risk, which leads to greater patient understanding and therefore may have a positive impact on health outcomes.

Abstract Background An organ sparing strategy has been proposed for patients with oesophageal cancer and a clinically complete response after neoadjuvant chemoradiotherapy (nCRT). This active surveillance strategy involves (repeated) oesophagogastroduodenoscopy (OGD) with bite-on-bite biopsies and endoscopic ultrasonography (EUS). The preSANO trial and preliminary results of the SANO trial concluded that these procedures are safe to identify those with a clinically complete response. However, the safety of these procedures beyond that timeframe remains unknown. The aim of this study is to assess the safety of endoscopic procedures after nCRT, extending beyond three months. Methods This is a retrospective multicentre cohort study. All patients who participated in the pre-SANO and SANO studies were included. All were treated with CROSS nCRT for oesophageal cancer and underwent (repeated) endoscopic response evaluations (OGD with bite-on-bite biopsies and/or EUS with fine needle aspiration, as indicated). Primary outcome was serious adverse events (SAE) as defined by Central Committee on Research Involving Human Subjects (CCMO) associated with endoscopic procedures which include (but are not limited to) bleeding, infection and perforation. Secondary outcome included mechanical injury. Results A total of 919 patients underwent at least one endoscopic response evaluation. Some 2355 endoscopic procedures (61% OGD with EUS combined, 33% OGD and 6% EUS) were performed. Of these, 819 (35%) were performed more than three months after nCRT. SAEs were reported for five endoscopic procedures (0.2%) and included three cases of gastrointestinal bleeding after OGD with biopsies and two cases with infection secondary to the endoscopic procedures. No significant difference in SAEs was found between the procedures conducted before and more than three months after nCRT (2 vs. 3, OR 2.8, 95% CI, 0.3 – 33.7, P = 0.35). Conclusion OGD with biopsies and EUS are both procedures which can be safely performed after nCRT during an active surveillance strategy.

Importance Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal. Objective To improve the implementation of guideline-based best practices in the Netherlands in pancreatic cancer care and assess the impact on survival. Design, setting, and participants This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients). Intervention The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care. Main Outcomes and Measures The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] global health score). Results Overall, 5887 patients with pancreatic cancer (median age, 72.0 [IQR, 64.0-79.0] years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio [OR], 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, −1.09, 95% CI, −3.05 to 0.94). Conclusions and Relevance In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options. Trial Registration ClinicalTrials.gov Identifier: NCT03513705

Background and AimMore insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling.MethodsA long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed.ResultsOverall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP.ConclusionDisease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.

Abstract Background Barrett’s esophagus (BE) with early neoplasia is an indication for endoscopic treatment. Patients with non-dysplastic BE are typically enrolled in an endoscopic surveillance program to enable early detection, and treatment, of BE related neoplasia. In contrast, a subset of patients with early BE neoplasia is concurrently diagnosed with BE and early neoplasia. Our goal was to distinguish cases detected through endoscopic surveillance programs (i.e. initial detection of non-dysplastic BE with progression to neoplasia later in time (metachronous neoplasia)) from cases where BE and neoplasia were diagnosed simultaneously (synchronous neoplasia). Methods We obtained data from the Dutch Barrett Expert Center Registry, a comprehensive nationwide registry encompassing data from all BE patients who underwent endoscopic treatment in Barrett expert Centers in the Netherlands. To enhance data completeness, we supplemented the registry with pathology reports sourced from the national pathology registry (PALGA). Primary endpoint was the proportion of patients diagnosed with BE and neoplasia simultaneously (synchronous neoplasia). Enrollment in an endoscopic surveillance program was defined as the presence of at least one endoscopy with non-dysplastic BE ≥12 months prior to endoscopic treatment initiation. Results A total of 2,091 patients were identified from the registry with a mean age of 66 years (SD±10) and 81% of the cohort being male. Median BE length was C2M5 (IQR 0-6; 3-8) and treatment indication encompassed low-grade dysplasia (LGD; 23%), high-grade dysplasia (HGD; 25%), or cancer (52%). Overall, 1149/2,091 patients (55%) underwent an endoscopy that revealed a new diagnosis of BE with synchronous neoplasia. Conversely, the remaining 942/2,091 patients (45%) were enrolled in endoscopic surveillance programs at the moment neoplasia was diagnosed, with a median duration of endoscopic surveillance prior to neoplasia detection of 8 years (IQR 4-13). The proportion of patients with new BE and synchronous neoplasia increased along with more severe histology at the moment of neoplasia detection. Specifically, the proportion of patients with synchronous neoplasia was 42% (198/475) for a treatment indication of LGD, 50% (260/520) for HGD and 63% (690/1096) for cancer (P <0.01). There was no significant difference observed concerning varying lengths of BE. Conclusions Remarkably, less than half of the patients with early Barrett’s neoplasia and neoplasia, receive a neoplasia diagnosis following enrollment in endoscopic surveillance programs, while the remaining patients present with de novo diagnosis of BE containing synchronous neoplasia. Notably, for patients with more severe histologic changes at the moment of neoplasia detection, the proportion of de novo BE with synchronous neoplasia is even higher. These findings support further critical view regarding the benefits of BE surveillance.

Aims The neoplastic progression risk in Barrett's Esophagus (BE) increases with increasing BE length. Therefore, some guidelines recommend that patients with ultra long-segment BE≥10cm (ULS-BE) are referred to an expert center, however, recommendations on further management are lacking. This study aimed to evaluate findings of an imaging endoscopy performed at a Barrett Expert Center (BEC), for patients with ULS-BE.

Background Currently data on the risk of progression to and lifetime risk of cancer are not available for patients with young onset Barrett's esophagus (BE). Our aim was to obtain epidemiologic data on the incidence of dysplasia or adenocarcinoma in young onset BE in the Netherlands by collecting data on all histologically confirmed cases over a prolonged period of 25 years between January 1, 1991 and December 31, 2015. Methods Data were obtained from the Dutch National Pathology Registry. Patients were included if there was a suspicion of BE visualized in the esophagus during the endoscopic examination in combination with a concordant histologic diagnosis of intestinal metaplasia. Results 231 patients with early onset BE were identified (median age 26 years [range 0-29 years]), with 17 progressing to dysplasia (6 prevalent and 11 incident). For the patients with incident dysplasia, the median surveillance time between the diagnosis of early onset BE and diagnosis of dysplasia was 5 years (range 0-16 years). The incidence rate of dysplasia was 7.3 per 1000 person-years. There were three patients who developed adenocarcinoma (1 prevalent and 2 incident), who were diagnosed at ages 28, 35, and 36 years. The incidence rate of adenocarcinoma was 1.3 per 1000 person-years. Conclusions In this 25-year period, 231 patients were diagnosed with early onset BE in the Netherlands, with 17 patients progressing to dysplasia and three developing adenocarcinoma. This corresponded to incidence rates of 7.3 per 1000 person-years for dysplasia and 1.3 per 1000 person-years for adenocarcinoma.

Abstract Background Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP). Methods This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up. Results After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life. Conclusion EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study.

Objective: The use and impact of antibiotics and the impact of causative pathogens on clinical outcomes in a large real-world cohort covering the entire clinical spectrum of necrotizing pancreatitis remain unknown. Summary Background Data: International guidelines recommend broad-spectrum antibiotics in patients with suspected infected necrotizing pancreatitis. This recommendation is not based on high-level evidence and clinical effects are unknown. Materials and Methods: This study is a post-hoc analysis of a nationwide prospective cohort of 401 patients with necrotizing pancreatitis in 15 Dutch centers (2010-2019). Across the patient population from the time of admission to 6 months postadmission, multivariable regression analyses were used to analyze (1) microbiological cultures and (2) antibiotic use. Results: Antibiotics were started in 321/401 patients (80%) administered at a median of 5 days (P25-P75: 1-13) after admission. The median duration of antibiotics was 27 days (P25-P75: 15-48). In 221/321 patients (69%) infection was not proven by cultures at the time of initiation of antibiotics. Empirical antibiotics for infected necrosis provided insufficient coverage in 64/128 patients (50%) with a pancreatic culture. Prolonged antibiotic therapy was associated with Enterococcus infection (OR 1.08 [95% CI 1.03-1.16], P=0.01). Enterococcus infection was associated with new/persistent organ failure (OR 3.08 [95% CI 1.35-7.29], P<0.01) and mortality (OR 5.78 [95% CI 1.46-38.73], P=0.03). Yeast was found in 30/147 cultures (20%). Discussion: In this nationwide study of patients with necrotizing pancreatitis, the vast majority received antibiotics, typically administered early in the disease course and without a proven infection. Empirical antibiotics were inappropriate based on pancreatic cultures in half the patients. Future clinical research and practice must consider antibiotic selective pressure due to prolonged therapy and coverage of Enterococcus and yeast. Improved guidelines on antimicrobial diagnostics and therapy could reduce inappropriate antibiotic use and improve clinical outcomes.

BACKGROUND:Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs.METHODS:The ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs.DISCUSSION:The ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting.TRIAL REGISTRATION:International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021.

INTRODUCTION:Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). AIM:assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. PATIENTS AND METHODS:Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014-2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). RESULTS:691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89-100%), SFM-b6 was 44% (20-77%), and SFM-b5+6 was 65% (53-90%). All centers met the performance target RAS>85%. Only 9 out of 17 met the performance target SFM-b5+6 > 85%. CONCLUSION:This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated.