Outcomes of Serum Food-Specific Immunoglobulin G 4 to Guide Elimination Diet in Patients With Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.

Common bile duct size in malignant distal obstruction and lumen-apposing metal stents: a multicenter prospective study.

Background and study aims Feasibility of EUS-guided choledochoduodenostomy (EUS-CDS) using available lumen-apposing stents (LAMS) is limited by the size of the common bile duct (CBD) (≤ 12 mm, cut-off for experts; 15 mm, cut-off for non-experts). We aimed to assess the prevalence and predictive factors associated with CBD size ≥ 12 and 15 mm in naïve patients with malignant distal biliary obstruction (MDBO). Patients and methods This was a prospective cohort study involving 22 centers with assessment of CBD diameter and subjective feasibility of the EUS-CDS performance in naïve jaundiced patients undergoing EUS evaluation for MDBO. Results A total of 491 patients (mean age 69 ±â€Š12 years) with mean serum bilirubin of 12.7 ±â€Š6.6 mg/dL entered the final analysis. Dilation of the CBD ≥ 12 and 15 mm was detected in 78.8 % and 51.9 % of cases, respectively. Subjective feasibility of EUS-CDS was expressed by endosonographers in 91.2 % for a CBD ≥ 12 mm and in 96.5 % for a CBD ≥ 15 mm. On multivariate analysis, age ( P  < 0.01) and bilirubin level ( P  ≤ 0.001) were the only factors associated with both CBD dilation ≥ 12 and ≥ 15 mm. These variables were poorly associated with the extent of duct dilation; however, based on them a prediction model could be constructed that satisfactorily predicted CBD size ≥ 12 mm in patients at least 70 years and a bilirubin level ≥ 7 mg/dL. Conclusions Our study showed that at presentation in a large cohort of patients with MDBO, EUS-CDS can be potentially performed in three quarters to half of cases by expert and less experienced endosonographers, respectively. Dedicated stents or devices with different designs able to overcome the limitations of existing electrocautery-enhanced LAMS for EUS-CDS are needed.

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non-academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432). CONCLUSION: This study shows that the 20-G FNB outperforms the 25-G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20-G FNB needle in both expert and lower volume EUS centers.

EUS-FNB with or without on-site evaluation for the diagnosis of solid pancreatic lesions (FROSENOR): Protocol for a multicenter randomized non-inferiority trial.

BACKGROUND: Rapid on-site evaluation (ROSE) of cytological specimensacquired with EUS-guided fine needle aspiration (EUS-FNA) represents the most accurate available technique to reach a definitive diagnosis in patients with pancreatic solid masses. Recently, needles with high histological yield have been developed for EUS-guided fine needle biopsy (EUS-FNB), with which the need for ROSE can be potentially overcome. AIMS: The primary aim is to compare the diagnostic accuracy of EUS-FNB with or without ROSE. The main endpoint will be measured against the gold standard diagnosis (surgical pathology whenever available or diagnostic work-up in agreement with a clinical course of at least six months). Secondary endpoints include: (a) safety; (b) presence of tissue core; (c) quality of specimens; (d) time of the sampling procedure. Reliability of macroscopic on-site evaluation (MOSE) by endosonographers will be also assessed. METHODS: FROSENOR is an international randomized non-inferiority ongoing study at sixteen centers in four continents. Eight hundred patients will be randomized in two arms (EUS-FNB + ROSE vs. EUS-FNB alone) and outcomes compared. Sample size has been calculated in order to demonstrate the non-inferiority of FNB alone. Randomization and data collection will be performed online. DISCUSSION: This study will ascertain if ROSE is still needed when performing EUS-FNB of solid pancreatic lesions.

Development, Validation, and Comparative Assessment of an International Scoring System to Determine Risk of Upper Gastrointestinal Bleeding.

BACKGROUND & AIMS: The Glasgow-Blatchford score (GBS) and pre-endoscopy Rockall score (pRS) are used in determining prognoses of patients with acute upper gastrointestinal bleeding, but neither predicts outcomes of patients with a high level of accuracy. A scoring system is needed to identify patients at risk of adverse outcomes and patients at low risk of harm. METHODS: We pooled data from 5 data sets in Canada, the United Kingdom, and Australia on 12,711 patients with acute upper gastrointestinal bleeding. The GBS and pRS were calculated for each patient. We performed multivariable logistic regression modeling of data from 10,639 cases to develop the new scoring system Canada - United Kingdom - Adelaide (CANUKA). We performed area under the receiver operating characteristic analyses to test the ability of CANUKA to identify patients who died or had rebleeding within 30 days, surgical or radiologic intervention to control bleeding, need for therapeutic endoscopy, and transfusion-a poor outcome was defined as 1 or more of these outcomes. Patients at low risk of a poor outcome (safe for management as an outpatient) were identified based on lack of transfusion, rebleeding, therapeutic endoscopy, interventional radiology or surgery, or death. We validated in 2072 patients from a separate cohort compiled from 2 datasets. RESULTS: In the development data set there was no difference between GBS and pRS in identifying patients who died without 30 days of bleeding (area under the receiver operating characteristic curve [AUROC], 0.67; 95% CI, 0.62-0.72 for GBS; AUROC, 0.70; 95% CI, 0.66-0.74 for pRS; P = .21). The GBS was superior to the pRS in identifying patients with rebleeding, hemostatic interventions, and transfusions. In the validation data set, CANUKA had higher accuracy than the GBS in identifying patients who died within 30 days of bleeding (AUROC, 0.77 vs 0.74; P = .047), but there was no significant difference in the accuracy of these scoring systems in identifying patients who required hemostatic intervention. The GBS more accurately identified patients who required therapeutic endoscopy (AUROC, 0.78; 95% CI, 0.76-0.81 for GBS; AUROC, 0.77; 95% CI, 0.74-0.79 for CANUKA; P = .47). For patients classified as low-risk patients by CANUKA (score ≤1), 96.3% were safely discharged, whereas 16 patients with a GBS ≤1 had an adverse outcome (a 95.3% probability of safe discharge). CONCLUSIONS: In an international validation analysis of the GBS and pRS for patients with acute upper gastrointestinal bleeding, we found the GBS to more accurately identify those who later required hemostatic interventions and transfusions; the scoring systems identified 30-day mortality or rebleeding with equal levels of accuracy. We developed a scoring system (CANUKA) that had similar performance to the GBS in predicting patient outcomes and it more accurately identifies patients at low risk for adverse outcomes.

A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device.

BACKGROUND AND AIMS: Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle. METHODS: Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders. RESULTS: A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P < .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836). CONCLUSION: The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

Management of pancreatic collections with a novel endoscopically placed fully covered self-expandable metal stent: a national experience (with videos).

BACKGROUND: Recent medical literature on novel lumen-apposing stents for the treatment of pancreatic fluid collections (PFCs) is limited by small numbers, solo operators, and single-center experience. OBJECTIVE: To evaluate a recently developed lumen-apposing, fully covered self-expandable metal stent (FCSEMS) in the management of PFCs. DESIGN: Retrospective case series. SETTING: Thirteen tertiary and private health care centers across Australia. PATIENTS: Forty-seven patients (median age 51 years) who underwent endoscopic management of PFCs. INTERVENTION: Insertion of FCSEMS after PFC puncture under EUS guidance. A subgroup of 9 patients underwent direct endoscopic necrosectomy. MAIN OUTCOME MEASUREMENTS: Technical and clinical success rate, adverse event rate. RESULTS: The technical success rate was 53 of 54 patients (98.1%), and the initial clinical success rate was 36 of 47 (76.6%), which was sustained for more than 6 months in 34 of 36 (94.4%). Early adverse events included 4 cases (7.4%) of stent migration during direct endoscopic necrosectomy, 4 cases (7.4%) of sepsis, 1 case (1.9%) of bleeding, and 1 case (1.9%) of stent migration into the fistula tract. Late adverse events were 6 (11.1%) spontaneous stent migrations, 3 (5.6%) recurrent stent occlusions, 3 (5.6%) tissue ingrowth/overgrowth, and 2 (3.7%) bleeding into PFC. The majority of stents inserted (48 of 54, 88.9%) and removed (31 of 35, 88.6%) in our study were described by the operator as superior to pigtail stents with regard to ease of use. LIMITATIONS: Retrospective study. CONCLUSION: Although FCSEMSs are technically easier to insert and remove compared with traditional pigtail stents, there are significant limitations to the widespread use of FCSEMSs in the management of PFCs. These include cost, adverse events, and lower-than-expected resolution rates.

Changing epidemiology of food bolus impaction: is eosinophilic esophagitis to blame?

BACKGROUND AND AIM: Data on the relationship between epidemiological changes in food bolus impaction (FBI) and its relationship to eosinophilic esophagitis (EoE) are limited. The aim of this study was to evaluate changes in the prevalence and etiology of FBI at the Royal Adelaide Hospital over 15 years. METHODS: Details of all patients who presented with FBI to Royal Adelaide Hospital (1996-2010) were reviewed from a prospective database. Detailed endoscopic and histological findings were examined for patients admitted under the Gastroenterology team. RESULTS: From 1996-2010, 539 patients were admitted. Prevalence of FBI increased overtime, with a male preponderance. The age at presentation was significantly lower in 2006-2010 (56.2 ± 1.6 years) compared with 2001-2005 (61.6 ± 1.9 years, P=0.03). There was a reduction in the proportion of patients with peptic-related stricture (from 75% [1996-2000] to 41% [2006-2010] [P<0.001]) and an increase in the prevalence of EoE (from 0% [1996-2000] to 35% [2006-2010], P<0.001). The proportion of patients who had esophageal biopsies taken at the index endoscopy also increased (8% [1996-2000] vs 28% [2001-2005] and 61% [2006-2010], P<0.01). There were no significant changes in rate of malignancy or post-surgical strictures. Endoscopic removal of food bolus was required in 86% of cases and, of these, 98% were successful with no complication or death. CONCLUSIONS: The prevalence of FBI has increased over the last 15 years. This was associated with an increased prevalence of EoE and a reduction in age of presentation and peptic-related strictures. These findings suggest that EoE is an important cause of FBI and that esophageal mucosal biopsy should be performed in all cases of FBI.