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BACKGROUND & AIMS: The combination of endoscopic resection and radiofrequency ablation is the treatment of choice for eradication of Barrett's esophagus (BE) with dysplasia and/or early cancer. Currently, there are no evidence-based recommendations on how to survey patients after successful treatment, and most patients undergo frequent follow-up endoscopies. We aimed to develop and externally validate a prediction model for visible dysplastic recurrence, which can be used to personalize surveillance after treatment. METHODS: We collected data from the Dutch Barrett Expert Center Registry, a nationwide registry that captures outcomes from all patients with BE undergoing endoscopic treatment in the Netherlands in a centralized care setting. We used predictors related to demographics, severity of reflux, histologic status at baseline, and treatment characteristics. We built a Fine and Gray survival model with least absolute shrinkage and selection operator penalization to predict the incidence of visible dysplastic recurrence after initial successful treatment. The model was validated externally in patients with BE treated in Switzerland and Belgium. RESULTS: A total of 1154 patients with complete BE eradication were included for model building. During a mean endoscopic follow-up of 4 years, 38 patients developed recurrent disease (1.0%/person-year). The following characteristics were independently associated with recurrence (strongest to weakest predictor): a new visible lesion during treatment phase, higher number of endoscopic resection treatments, male sex, increasing BE length, high-grade dysplasia or cancer at baseline, and younger age. External validation showed a C-statistic of 0.91 (95% confidence interval, 0.86-0.94) with good calibration. CONCLUSIONS: This is the first externally validated model to predict visible dysplastic recurrence after successful endoscopic eradication treatment of BE with dysplasia or early cancer. On external validation, our model has good discrimination and calibration. This model can help clinicians and patients to determine a personalized follow-up strategy. ispartof: GASTROENTEROLOGY vol:163 issue:1 pages:285-294 ispartof: location:United States status: published

Background Endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most patients with Barrett’s esophagus (BE). However, some patients experience poor healing and/or poor squamous regeneration. We evaluated incidence and treatment outcomes of poor healing and poor squamous regeneration. Methods We included all patients treated with RFA for early BE neoplasia from a nationwide Dutch registry based on a joint treatment protocol. Poor healing (active inflammatory changes or visible ulcerations ≥ 3 months post-RFA), poor squamous regeneration ( Results 1386 patients (median BE C2M5) underwent RFA with baseline low grade dysplasia (27 %), high grade dysplasia (30 %), or early cancer (43 %). In 134 patients with poor healing (10 %), additional time and acid suppression resulted in complete esophageal healing, and 67/134 (50 %) had normal squamous regeneration with 97 % CE-BE. Overall, 74 patients had poor squamous regeneration (5 %). Compared with patients with normal regeneration, patients with poor squamous regeneration had a higher risk for treatment failure (64 % vs. 2 %, relative risk [RR] 27 [95 % confidence interval [CI] 18–40]) and progression to advanced disease (15 % vs. Conclusions In half of the patients with poor healing, additional time and acid suppression led to normal squamous regeneration and excellent treatment outcomes. In patients with poor squamous regeneration, however, the risk for treatment failure and progression to advanced disease was significantly increased.

ObjectiveRadiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett’s oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting.DesignEndoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included.ResultsAfter ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0–1; 1–2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22–69) and 4 endoscopies (1–5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk.ConclusionIn a setting of centralised care, RFA±ER is effective for eradication of Barrett’s related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value.Netherlands trial register numberNL7039.

Purpose of review Gastric outlet obstruction is a syndrome that is caused by several benign and malignant diseases. Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) is a novel treatment that seems to combine the advantages of the two traditional treatments: enteral stent placement (ES) and surgical gastrojejunostomy (SGJ). This review aims to determine the current position of EUS-GE amidst the two traditional treatment options. Recent findings Different approaches can be adopted to facilitate EUS-GE. Direct gastroenterostomy seems to have the shortest procedure time. All methods possess high technical success rates. Several retrospective analyses have compared EUS-GE to ES and SGJ. EUS-GE seems to have better stent patency compared to ES and a lower adverse event rate compared to SGJ. Recently, randomized trials have been initiated which compare EUS-GE with ES or SGJ. Summary Although the currently published literature unequivocally shows the great promises of EUS-GE, properly powered and controlled studies are warranted to ascertain the definitive position of EUS-GE within the treatment repertoire of GOO. Until reliable data has been collected, EUS-GE can be considered a safe and effective alternative to ES and SGJ.

BACKGROUND & AIMS: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is safe and leads to complete eradication in the majority of patients. However, a subgroup will experience a more complex treatment course with a risk for failure or disease progression. Early identification of these patients may improve patient counseling and treatment outcomes. We aimed to develop a prognostic model for a complex treatment course. METHODS: We collected data from a nationwide registry that captures outcomes for all patients undergoing endoscopic eradication therapy for early BE neoplasia. A complex treatment course was defined as neoplastic progression, treatment failure, or the need for endoscopic resection during the radiofrequency ablation treatment phase. We developed a prognostic model using logistic regression. We externally validated our model in an independent registry. RESULTS: A total of 1386 patients were included, of whom 78 (6%) had a complex treatment course. Our model identified patients with a BE length of 9 cm or longer with a visible lesion containing high-grade dysplasia/cancer, and patients with less than 50% squamous conversion after radiofrequency ablation were identified as high risk for a complex treatment. This applied to 8% of the study population and included 93% of all treatment failures and 76% of all patients with advanced neoplastic progression. The model appeared robust in multiple sensitivity analyses and performed well in external validation (area under the curve, 0.84). CONCLUSIONS: We developed a prognostic model that identified patients with a BE length of 9 cm or longer and high-grade dysplasia/esophageal adenocarcinoma and those with poor squamous regeneration as high risk for a complex treatment course. The good performance in external validation suggests that it may be used in clinical management (Netherlands Trial Register: NL7039). ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:20 issue:11 pages:2495-+ ispartof: location:United States status: published

Background The optimal management for patients with low grade dysplasia (LGD) in Barrett’s esophagus (BE) is unclear. According to the Dutch national guideline, all patients with LGD with histological confirmation of the diagnosis by an expert pathologist (i. e. “confirmed LGD”), are referred for a dedicated re-staging endoscopy at an expert center. We aimed to assess the diagnostic value of re-staging endoscopy by an expert endoscopist for patients with confirmed LGD. Methods This retrospective cohort study included all patients with flat BE diagnosed in a community hospital who had confirmed LGD and were referred to one of the nine Barrett Expert Centers (BECs) in the Netherlands. The primary outcome was the proportion of patients with prevalent high grade dysplasia (HGD) or cancer during re-staging in a BEC. Results Of the 248 patients with confirmed LGD, re-staging in the BEC revealed HGD or cancer in 23 % (57/248). In 79 % (45/57), HGD or cancer in a newly detected visible lesion was diagnosed. Of the remaining patients, re-staging in the BEC showed a second diagnosis of confirmed LGD in 68 % (168/248), while the remaining 9 % (23/248) had nondysplastic BE. Conclusion One quarter of patients with apparent flat BE with confirmed LGD diagnosed in a community hospital had prevalent HGD or cancer after re-staging at an expert center. This endorses the advice to refer patients with confirmed LGD, including in the absence of visible lesions, to an expert center for re-staging endoscopy.

Introduction After endoscopic resection (ER) of neoplasia in Barrett’s esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. Methods Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. Results Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11–51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. Conclusion In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation.

Background and Aims High rates of technical and clinical success were reported for lumen-apposing metal stent (LAMS) placement for peripancreatic fluid collection (PFC) drainage. However, data on the adverse event (AE) rates are heterogeneous. The aim of this study was to evaluate the incidence, severity, management, and risk factors of AEs related to the use of LAMSs for drainage of PFCs in a large cohort of patients. Methods This is a multicenter, international, retrospective review from 15 centers of all patients who underwent placement of LAMSs for the management of PFCs. A nested case-control study was conducted in patients with (case) or without (control) AEs. Results Three hundred thirty-three procedures in 328 patients were performed (5 patients treated with 2 LAMSs). Technical success was achieved in 321 patients (97.9%). Three hundred four patients were finally included in the study (7 excluded for lost to follow-up information; 10 excluded for deaths unrelated to LAMSs). The rate of clinical success was 89.5%. Seventy-nine LAMS-related AEs occurred in 74 of 304 patients (24.3%), after a mean time of 25.3 days (median, 18 days; interquartile range, 6-30) classified as 20 (25.3%) mild, 54 (68.4%) moderate, or 5 (6.3%) severe. On multivariable analysis compared with control subjects, cases were more likely to have walled-off necrosis (WON) versus pancreatic pseudocysts (odds ratio, 2.18; 95% confidence interval, 1.09-4.46; P = .028), whereas cases were less likely to have undergone tract (balloon) dilation (yes vs no; odds ratio, .47; 95% confidence interval, .22-.93; P = .034). Conclusions Data from this large international retrospective study confirm that the use of LAMSs for management of PFCs has excellent technical and good clinical success rates. The rate of AEs, however, is not negligible and should be carefully considered before using these stents for drainage of PFCs and in particular for WON. Further prospective studies are needed to confirm these findings. (Clinical trial registration number: NCT 03544008.)

Endoscopic dilation (ED) is still the mainstay of therapeutic management of benign esophageal strictures (BESs). This study aimed to establish risk factors for refractory BESs and assess long-term clinical outcomes of ED.We performed a retrospective study in 891 patients who underwent ED from 2003 to 2018 for BESs. We searched electronic medical records in 6 tertiary care centers in the Netherlands for data on clinical outcome of ED. Median follow-up was 39 months. The primary endpoint was risk factors for refractory BESs, defined as factors associated with an increased number of ED sessions during follow-up. Secondary endpoints were time from first to last ED session and adverse events.Dilation up to 13 to 15 mm was associated with a higher number of ED sessions than dilation up to 16 to 18 mm (5.0 vs 4.1; hazard ratio [HR], 1.4; P = .001). Compared with peptic strictures, anastomotic (4.9 vs 3.6; HR, 2.1; P .001), radiation (5.0 vs 3.6; HR, 3.0; P .001), caustic (7.2 vs 3.6; HR, 2.7; P .001), and postendotherapy (3.9 vs 3.6; HR, 1.8; P = .005) strictures were associated with a higher number of ED sessions. After 1 year of follow-up, the proportions of patients who remained free of ED was 75% in anastomotic, 71% in radiation, 70% in peptic, 83% in postendotherapy, and 62% in caustic strictures. Esophageal perforation occurred in 23 ED sessions (.4%) in 22 patients (2.4%).More than 60% of patients with BESs remain free of ED after 1 year of follow-up. Because dilation up to 16 to 18 mm diameter was associated with fewer ED sessions during follow-up, we suggest that clinicians should consider dilation up to at least 16 mm to reduce the number of ED sessions in these patients.

Item does not contain fulltext In recent years, new guidelines and recommendations have been published regarding the diagnostic criteria and therapeutic management of eosinophilic esophagitis (EoE). The aim of this study is to assess the diagnostic and therapeutic management of patients diagnosed with EoE in daily clinical practice and whether this was performed according to current guidelines and recommendations. A population-based, multicenter retrospective cohort study was conducted using data from the national pathology registry (PALGA), medical records, and telephone interviews of patients diagnosed with EoE in two academic and two nonacademic hospitals in the period 2004 to 2014. The study was approved by all involved ethical committees. Data regarding demographics, clinical manifestations, endoscopic results, histologic samples, and therapeutic strategies were collected. Standard statistical analyses were performed to summarize patient characteristics. We included 119 patients diagnosed with EoE in this study. The median age at onset of symptoms was 29 years (IQR: 15-42) and the median age at diagnosis was 38 years (IQR: 23-51 years), leading to a median diagnostic patients' delay of 6.5 years (IQR: 2-14 years). The median physicians' delay in diagnosis between first contact in the hospital and diagnosis was 1.0 year (IQR: 1-7 years). The incidence of newly diagnosed patients with EoE increased steadily over a period of 11 years. Criteria for the microscopic diagnosis of EoE varied between pathologists in each hospital. Initial treatment included topical corticosteroids (TCS) (30.3%), proton pump inhibitors (PPI) (29.4%), or a combination (10.1%). A follow-up endoscopy was performed in 40.3% of patients. During follow-up, treatment included PPIs (76.0%), TCS (59.6%), a combination of PPIs and TCS (45.4%), and endoscopic dilations (6.7%). Diagnostic and therapeutic discrepancies between daily clinical practice and recommendations from current and past guidelines were observed. Apart from developing guidelines, efforts should be undertaken to implement these in daily clinical practice.

Objectives: Studies on the impact of rapid on-site evaluation (ROSE) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of lymph nodes are retrospective and have shown conflicting results. We aimed to compare the diagnostic yield of EUS-FNA of lymph nodes with ROSE (ROSE+) and without ROSE (ROSE-). Methods: This was a multicenter, randomized controlled trial. Consecutive patients who were scheduled to undergo EUS-FNA of mediastinal or abdominal lymph nodes were randomized to ROSE+ or ROSE-. In the ROSE+ group, the number of passes was dictated by the on-site cytotechnician. In the ROSE- group, five passes were performed without interference from the cytotechnician. All samples were reviewed by a single-expert cytopathologist, blinded to group allocation. Primary endpoint was diagnostic yield with and without ROSE. Results: After inclusion of 90 patients, interim analysis showed futility of study continuation since diagnostic yield of ROSE+ and ROSE- were comparable. A total of 91 patients were randomized to ROSE+ (N = 45) or ROSE- (N = 46). Diagnostic yield of ROSE+ and ROSE- and diagnostic accuracy were comparable: 93.3% vs. 95.7% (P = 0.68) and 97.6% vs. 93.2% (P = 0.62), respectively. Two major complications (one per group) occurred (p = 0.99). ROSE- patients more often reported self-limiting post-procedural pain (p < 0.001). Median procedure time for ROSE+ (20 min) and ROSE- (23 min) was comparable (P = 0.06). Median time to review slides in the ROSE- group (12:47 min) was longer than with ROSE+ (7:52 min) (P < 0.001). Mean costs of ROSE- and ROSE+ were comparable: €938.29 (±172.70) vs. €945.98 (±223.38) (P = 0.91), respectively. Conclusions: Diagnostic yield and accuracy of EUS-FNA of mediastinal and abdominal lymph nodes with and without ROSE are comparable. Time needed to review slides was shorter and post-procedural pain was less often reported in the ROSE+ group. Based on the primary outcome, the implementation of ROSE during EUS-FNA of mediastinal and abdominal lymph nodes cannot be advised.

Item does not contain fulltext BACKGROUND: The clinical management of patients with non-obstructive dysphagia is notoriously difficult. Esophageal impedance measurement can be used to measure esophageal bolus transit without the use of radiation exposure to patients. However, validation of measurement of bolus transit with impedance monitoring has only been performed in healthy subjects with normal motility and not in patients with dysphagia and esophageal motility disorders. The aim was, therefore, to investigate the relationship between transit of swallowed liquid boluses in healthy controls and in patients with dysphagia. METHODS: Twenty healthy volunteers and 20 patients with dysphagia underwent concurrent impedance measurement and videofluoroscopy. Each subject swallowed five liquid barium boluses. The ability of detecting complete or incomplete bolus transit by means of impedance measurement was assessed, using radiographic bolus transit as the gold standard. KEY RESULTS: Impedance monitoring recognized stasis and transit in 80.5% of the events correctly, with 83.9% of bolus transit being recognized and 77.2% of stasis being recognized correctly. In controls 79.8% of all swallows were scored correctly, whereas in patients 81.3% of all swallows were scored correctly. Depending on the contractility pattern, between 77.0% and 94.3% of the swallows were scored correctly. CONCLUSIONS & INFERENCES: Impedance measurement can be used to assess bolus clearance patterns in healthy subjects, but can also be used to reliably assess bolus transit in patients with dysphagia and motility disorders.

Gastroesophageal reflux is considered to be the most common gastrointestinal cause of non-cardiac chest pain (NCCP). It remains unclear why some reflux episodes in the same patient cause chest pain while others do not. To understand more about the mechanisms by which reflux elicits chest pain, we aimed to identify factors which are important in triggering chest pain. In this multicenter study, 120 patients with NCCP were analyzed using 24-h pH-impedance monitoring. In the patients with a positive association between reflux and chest pain, the characteristics of the reflux episodes which were followed by a chest pain episode were compared with chest pain-free reflux episodes. Using 24-h pH-impedance monitoring, 40% of the NCCP patients were identified as having reflux as a possible cause of their chest pain. Reflux episodes that were associated with chest pain had a higher proximal extent (P=0.007), a higher volume clearance time (P=0.030), a higher 15-minute acid burden (P=0.041), were more often acidic (P=0.011), had a lower nadir pH (P=0.044), and had a longer acid duration time (P=0.027) than reflux episodes which were not followed by chest pain. Patients who experienced typical reflux symptoms were more likely to have reflux as the cause of their chest pain (52 vs. 31.4%, P=0.023). The presence of a larger volume of acid refluxate for a longer period of time appears to be an important determinant of perceiving a reflux episode as chest pain. 24-h pH-impedance monitoring is an important tool in identifying gastroesophageal reflux as a potential cause of symptoms in patients with NCCP

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

Background It is common belief that symptoms of patients with non-obstructive dysphagia are the result of impaired bolus clearance in the esophagus, usually caused by esophageal motility disorders. We therefore investigated the relationship between transit of swallowed boluses and the symptom dysphagia. Methods Twenty healthy volunteers and 20 patients with dysphagia underwent videofluoroscopy. Success of bolus transport was graded on a 7-point scale. Each subject swallowed five liquid and five solid barium boluses. Key Results For liquids, patients reported dysphagia during 1 [0–3] of the five swallows, while controls reported no dysphagia (median 0 [0–0]; p = 0.003). For solids, patients reported dysphagia during 3 [2–4] of five swallows, while controls reported dysphagia in 0.5 [0–2] of five swallows (p = 0.001). When correlating dysphagia to ineffective clearance (score ≥3), in 3 [2–4] of five liquids, the subjects perception of clearance was related to the clearance result on fluoroscopy in patients and also 3 [1–5] were correctly perceived in controls (p = 0.6). For solids, in 4 [3–5] of five swallows, the subjects perception of clearance was related to the clearance result on fluoroscopy in patients, but only 2 [1–3] of five swallows were correctly perceived by controls, the difference being statistically significant. Conclusions & Inferences Patients very frequently report dysphagia when bolus clearance is successful. Therefore, the major underlying problem in patients with non-obstructive dysphagia is disordered perception and increased sensitivity to physiological bolus stasis. Treatment should therefore be directed at reducing increased sensitivity rather than at improving motility.

INTRODUCTION Radiofrequency ablation (RFA) is a valuable treatment option in Barrett's esophagus resulting in eradication of dysplasia and conversion of all Barrett's epithelium into normal squamous epithelium. In Barrett's esophagus, esophageal impedance monitoring is hampered by low baseline impedance values. Whether these low baselines are caused by an intrinsically low impedance of cylindrical epithelium or by the excessive reflux itself is hitherto unknown. Data on esophageal motility after RFA are scarce. Our aim was to examine the effect of RFA on esophageal motility and esophageal baseline impedance in patients with Barrett's esophagus. METHODS In 10 patients, conventional esophageal manometry and 24-h pH-impedance measurements were performed before and after RFA. The number and type of reflux episodes were assessed and baseline impedance values were measured in all recording segments. In another five patients, high-resolution manometry was performed before and after RFA. RESULTS Complete regression of all Barrett's epithelium was achieved in all 15 patients after 3 ± 1 RFA sessions. Overall, no significant motility changes were found after RFA. Patients had excessive acid exposure times before and after RFA [25 (17-42) and 16 (9-24)%, respectively]. Baseline esophageal impedance values were low, with the lowest values in the distal recording segments. RFA increased baseline impedance in all recording segments in the upright position; in the supine position, the effect just failed to reach statistically significant levels. CONCLUSION RFA did not alter esophageal motility significantly. Low esophageal baseline impedance levels in patients with Barrett's esophagus reflect, at least in part, intrinsic impedance properties of cylindrical epithelium, as baselines increased after conversion into neosquamous epithelium.

Item does not contain fulltext Background and aims In multiple endocrine neoplasia type 1 (MEN1), endoscopic ultrasound (EUS) is used for identification and follow-up of pancreatic neuroendocrine tumors (PNETs). The role of EUS in surveillance of small ( < 20 mm) PNETs is unclear, mostly because the natural course of these lesions is largely unknown. We aimed to determine annual growth and incidence rate of small PNETs in patients with MEN1 using EUS-based surveillance. Patients and methods Linear array EUS procedures in patients with MEN1 between 2002 and 2015 were identified. Number, size, and location of PNETs were recorded. Annual growth of PNETs < 20 mm identified at the initial EUS ("prevalent" PNETs) and during follow-up ("incident" PNETs) was calculated using mixed model linear regression analysis. Results A total of 54 patients were identified and 38 patients were included. In all, 226 PNETs were identified (median size 5.0 mm, interquartile range 3.7 - 7.5) of which 124 (55 %) were prevalent and 102 (45 %) were incident PNETs. Annual incidence rate was 0.79 PNETs/year (95 % confidence interval [CI] 0.73 to 0.87). Overall growth rate was 0.10 mm/year (95 %CI 0.02 to 0.19; P = 0.01); PNETs < 10 mm (n = 198) did not grow (P = 0.23), whereas PNETs >/= 10 mm (n = 28) grew 0.44 mm/year (95 %CI 0.10 to 0.78; P = 0.01). Prevalent PNETs grew 0.21 mm/year (95 %CI 0.10 - 0.32; P < 0.001), whereas incident PNETs did not grow (P = 0.26). Conclusions The annual growth rate of small, solid PNETs in patients with MEN1 is lower than previously thought. Surveillance intervals could probably be prolonged without compromising safety.

Background Non-obstructive dysphagia patients prove to be a difficult category for clinical management. Esophageal high-resolution manometry (HRM) is a novel method, used to analyze dysphagia. However, it is not yet clear how findings on HRM relate to bolus transport through the esophagus. Methods Twenty healthy volunteers and 20 patients with dysphagia underwent HRM and videofluoroscopy in a supine position. Each subject swallowed five liquid and five solid barium boluses. Esophageal contraction parameters and bolus transport were evaluated with HRM and concurrent videofluoroscopy. Key Results Stasis of liquid and solid barium boluses occurred in patients and in healthy volunteers in 64% and 41% and in 84% and 82% of the swallows, respectively. Overall, 70% of the liquid and 72% of the solid bolus swallows were followed by a peristaltic contraction, the difference not being statistically significant. Statistically significant associations were found for transition zone length of liquid and solid boluses, and for DCI and distal contraction amplitudes for liquid stasis. No correlation was found between the degree of stasis and other manometric parameters. Conclusions & Inferences Stasis of both liquid and solid boluses occurs frequently in patients and in controls and can be regarded as physiological. Motility patterns can predict the effectiveness of bolus transit and level of stasis to some degree but the relationship between esophageal motility and transit is complex and far from perfect. Esophageal manometry is therefore currently deemed unfit to be used for the prediction of bolus transit, and should rather be used for the identification of treatable esophageal motility disorders.

Background Esophageal high-resolution manometry (HRM) is a novel method for esophageal function testing that has prompted the development of new parameters for quantitative analysis of esophageal function. Until now, the reproducibility of these parameters has not been investigated. Methods Twenty healthy volunteers underwent HRM on two separate days. Standard HRM parameters were measured. In addition, in conventional (virtual) line tracings, lower esophageal sphincter (LES) resting pressure, relaxation pressure, and relative relaxation pressure were measured. Firstly, for each variable, the mean percentage of covariation (100 × SD/mean: %COV) was derived as a measure of inter- and intra-individual variation. Secondly, Kendall’s coefficients of concordance (W values) were calculated. Thirdly, Bland–Altman plots were used to express concordance graphically. Key Results Statistically significant concordance values were found for upper esophageal sphincter (UES) pressure (W = 0.90, P = 0.02), transition zone length (W = 0.92, P = 0.01), LES length (W = 0.81, P = 0.04), LES pressure (W = 0.75, P = 0.05), LES relaxation pressure (W = 0.75, P = 0.03), relative LES relaxation pressure (W = 0.78, P = 0.05), gastric pressure (W = 0.81, P = 0.04), and contraction amplitude 5 cm above the LES (W = 0.86, P = 0.03). In conventional setting, only LES resting pressure (W = 0.835, P = 0.03) proved significant. In HRM tracings, concordance values for contraction wave parameters, and in conventional line tracings, LES relaxation pressure and relative relaxation pressure did not reach levels of statistical significance. Conclusions & Inferences Esophageal HRM yields reproducible results. Parameters that represent anatomic structures show better reproducibility than contraction wave parameters. The reproducibility of LES resting and relaxation pressure assessed with HRM is better than with conventional manometry and further supports the clinical use of HRM.

Item does not contain fulltext BACKGROUND AND AIM: Pneumatic dilation is a commonly used treatment in achalasia. Recent studies have shown that esophageal distensibility measurements can be used to assess the effect of dilation and possibly the risk of perforation. A new hydraulic dilation balloon allows visualization of the shape of the balloon in vivo and measurement of distensibility during dilation. We aimed to evaluate the technical feasibility of a 30-mm shape-measuring hydraulic dilation balloon for the treatment of achalasia. METHODS: Consecutive patients with newly diagnosed achalasia were dilated using a 30-mm shape-measuring hydraulic dilation balloon. Patients were contacted 1 week, 1 month, and 3 months after dilation. Technical success, clinical success, and major complications were evaluated. RESULTS: Technical success was achieved in all of the 10 patients included. Median esophagogastric junction distensibility (mm(2)/mmHg) increased from 1.1 (IQR 0.6 - 1.3) before dilation therapy to 7.0 (IQR 5.5 - 17.8) afterwards (P = 0.005). No major complications were seen. Three patients (30 %) reported recurrent dysphagia. CONCLUSION: Hydraulic dilation with a shape-measuring balloon in achalasia patients is feasible. In vivo esophageal distensibility measurements may allow for an individualized, patient-specific dilation regimen.The Netherlands National Trial Register: NTR4371.

Item does not contain fulltext BACKGROUND: A previous single-centre study showed that lower oesophageal sphincter electrical stimulation therapy (LES-EST) in gastro-oesophageal reflux disease (GERD) patients improves reflux symptoms and decreases oesophageal acid exposure. AIM: To evaluate safety and efficacy of LES-EST in GERD patients with incomplete response to proton pump inhibitors (PPIs) in a prospective, international, multicentre, open-label study. METHODS: GERD patients, partially responsive to PPIs, received LES-EST. GERD health-related quality of life (GERD-HRQL), daily symptom diaries, quality of life scores, oesophageal acid exposure, and LES resting and residual pressure were measured before and after initiation of LES-EST. Stimulation sessions were optimised based on residual symptoms and oesophageal acid exposure. RESULTS: Forty-four patients were enrolled and 6-month data from 41 patients are available. Hiatal repair was performed in 16 patients. One device-related, one procedure-related and one unrelated severe adverse event were reported. GERD-HRQL improved from 31.0 (IQR 26.2-36.8) off-PPI and 16.5 (IQR 9.0-22.8) on-PPI to 4 (IQR 1-8) at 3-month and 5 (IQR 3-9) at 6-month follow-up (P < 0.0001 vs. on- and off-PPI). Oesophageal acid exposure (pH < 4.0) improved from 10.0% (IQR 7.5-12.9) to 3.8% (IQR 1.9-12.3) at 3 months (P = 0.0027) and 4.4% (IQR 2.2-7.2) at 6 months (P < 0.0001). CONCLUSIONS: These interim results show an acceptable safety record of LES-EST to date, combined with good short-term efficacy in GERD patients who are partially responsive to PPI therapy. A remarkable reduction in regurgitation symptoms, without the risk of intervention-requiring dysphagia may prove to be an advantage compared with other anti-reflux procedures. ClinicalTrials.gov Identifier: NCT01574339.

Various treatment modalities are currently being used in patients with gastroesophageal reflux disease (GERD); however, long-term outcome is not clear. The aim is to evaluate long-term results of GERD treatments with regard to reflux symptoms, use of anti-reflux medication and anti-reflux surgery outcome.Patients who had undergone 24-h pH monitoring for reflux symptoms between January 2002 and March 2012 were invited to fill out the Reflux Disease Questionnaire (RDQ) and a general questionnaire. Patients with and without anti-reflux surgery were compared using multiple linear and logistic regression models.In total, 1027 of 2190 included patients (47%) returned the questionnaires. After exclusion due to predefined criteria, 477 patients were analyzed. Median total RDQ score was 18 points (10.2% symptom-free) in the conservative group (n = 304) and 10 points (31.2% symptom-free) in the surgical group (n = 173) after a mean follow up of 5.1 years. Daily proton pomp inhibitor (PPI) use was higher in the conservative group than in the surgical group (80.9% vs. 51.4%, p = 0.000). Linear regression analysis showed an association between RDQ scores and anti-reflux surgery (β = -5.477, p = 0.001) and male gender (β = -4.306, p = 0.006). Logistic regression analyses showed that daily PPI use was lower in patients who underwent anti-reflux surgery (odds ratio [OR] = 0.24, p = 0.000), while it increased with age (OR = 1.03, p = 0.000).There is still a high prevalence of typical reflux symptoms and daily PPI use in GERD patients after5 years of follow up. Male patients and patients who had undergone anti-reflux surgery were more often asymptomatic. Daily PPI use was lower after anti-reflux surgery, while it increased with age.

Objective. One of the main causes of persistent cough is gastro-oesophageal reflux. In these patients, excessive oesophageal acid exposure and/or a temporal association between gastro-oesophageal reflux and cough can be demonstrated during 24-h pH monitoring. Impedance pH monitoring may have a higher yield than pH monitoring alone, but this technique is not yet widely available. The aim of this study was to assess the diagnostic yield of ambulatory 24-h oesophageal pH monitoring for the evaluation of chronic unexplained cough. Material and methods. Twenty-four-hour pH monitoring studies were analysed in 55 patients with chronic cough. In 14 of these studies concurrent ambulatory pressure monitoring was done. A cough episode was considered to be related to reflux if the cough occurred within two minutes after the onset of the reflux episode ("reflux-cough sequence''). Temporal relationships between cough and reflux were expressed by using the symptom association probability (SAP). Results. Thirty-seven patients actually coughed during the 24-h study. Eleven patients (20%) had a positive SAP for the reflux-cough sequence. In 5 patients, reflux followed coughing. Pathological oesophageal acid exposure was found in 15 subjects. Interestingly, only a minority (39.2%) of the cough bursts detected manometrically were marked by patients who had undergone both combined 24-h pH and pressure recording. Conclusions. This study shows that, in a routine clinical setting, combined 24-h pH and pressure monitoring is useful in the evaluation of patients with chronic unexplained cough, as positive findings are not infrequently found and have diagnostic and therapeutic consequences.

Background Esophageal high-resolution manometry (HRM) is a novel method to assess esophageal motility. Several software and hardware systems are currently available. A set of normal values for HRM parameters was established in the US, using proprietary tactile-sensing catheter technology (Given Imaging). We wished to determine normal values for HRM performed with another type of catheter (Unisensor). Methods Fifty-two healthy volunteers underwent supine HRM. Each subject swallowed 10 liquid water boluses. Esophageal contraction parameters were evaluated and normal values were calculated (defined as 5th and 95th percentile of values). Key Results The normal range for the following parameters was calculated; distal contractile integral (mean 1319.44, with a 5-95th percentile range [185.65-3407.60]), contractile front velocity (mean 3.98, 5-95th percentile range [2.40-6.50]), Intrabolus pressure (mean 9.68, range [1.00-19.00]), contraction amplitude measured 5 cm above the esophagogastric junction (EGJ; mean 78.76, range [23.00-146.00]), contraction amplitude 15 cm above the EGJ (mean 43.66, range [3.60-96.00]), transition zone (TZ) length (mean 1.34, range [0.00-5.63]), upper esophageal sphincter (UES) pressure (mean 81.63, range [19.50-165.10]), EGJ length (mean 2.97, range [2.17-4.00]), EGJ resting pressure (mean 29.35, range [8.95-51.40]), EGJ relaxation pressure (mean 16.79, range [1.00-39.35]), IRPs4 (mean 13.42, range [2.59-28.28]), and gastric pressure (mean 5.06, range [0.00-9.46]). Conclusions & Inferences Overall, the normal values of esophageal HRM parameters obtained with the Unisensor catheter resemble those of the previously published series. Marked differences in upper limits of normal were found for parameters related to the esophageal sphincters and TZ length. Users of HRM should be aware of these differences and define pathology based on comparison to appropriate normal values.