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BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.
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Cistadenoma Seroso , Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Cistadenoma Seroso/diagnóstico , Estudios Prospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Quiste Pancreático/diagnóstico , Quiste Pancreático/genética , Quiste Pancreático/terapia , Secuenciación de Nucleótidos de Alto Rendimiento , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Genómica , Proteínas Quinasas Activadas por Mitógenos/genéticaRESUMEN
BACKGROUND AND AIMS: The application of endoscopic suturing has revolutionized defect closures. Conventional over-the-scope suturing necessitates removal of the scope, placement of the device, and reinsertion. A single channel, single sequence, through-the-scope suturing device has been developed to improve this process. This study aims to describe the efficacy, feasibility, and safety of a through-the-scope suturing device for gastrointestinal defect closure. METHODS: This was a retrospective multicenter study involving 9 centers of consecutive adult patients who underwent suturing using the X-Tack Endoscopic HeliX Tacking System (Apollo Endosurgery). The primary outcomes were technical success and long-term clinical success. Secondary outcomes included adverse events, recurrence, and reintervention rates. RESULTS: In all, 56 patients (mean age 53.8, 33 women) were included. Suturing indications included fistula repair (n=22), leak repair (n=7), polypectomy defect closure (n=12), peroral endoscopic myotomy (POEM) site closure (n=7), perforation repair (n=6), and ulcers (n=2). Patients were followed at a mean duration of 74 days. Overall technical and long-term clinical success rates were 92.9% and 75%, respectively. Both technical and clinical success rates were 100% for polypectomies, POEM-site closures, and ulcers. Success rates were lower for the repair of fistulas (95.5% technical, 54.5% clinical), leaks (57.1%, 28.6%), and perforations (100%, 66.7%). No immediate adverse events were noted. CONCLUSION: This novel, through-the-scope endoscopic suturing system, is a safe and feasible method to repair defects that are ≤3 cm. The efficacy of this device may be better suited for superficial defects as opposed to full-thickness defects. Larger defects will need more sutures and probably a double closure technique to provide a reinforcement layer.
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OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.
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Quiste Pancreático , Neoplasias Pancreáticas , Humanos , ARN , Detección Precoz del Cáncer , Quiste Pancreático/diagnóstico , Quiste Pancreático/genética , Quiste Pancreático/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias PancreáticasRESUMEN
BACKGROUND AND AIMS: During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies. METHODS: Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence. RESULTS: Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%). CONCLUSIONS: N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms.
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COVID-19 , Gastroenterólogos , Respiradores N95 , Exposición Profesional , Colonoscopía , Electrocardiografía , Frecuencia Cardíaca , Humanos , Exposición Profesional/prevención & controlAsunto(s)
Centros Médicos Académicos/normas , Éxito Académico , Benchmarking/normas , Educación Médica/normas , Gastroenterología/educación , Gastroenterología/normas , Indicadores de Calidad de la Atención de Salud/normas , Humanos , National Institutes of Health (U.S.)/normas , Apoyo a la Investigación como Asunto/normas , Estados Unidos , Lugar de Trabajo/normasRESUMEN
Background: Gastrointestinal bleeding (GIB) is a common complication after placement of a left ventricular assist device (LVAD). Some institutions attempt to mitigate post-LVAD GIB using preoperative endoscopy. Our study evaluated whether preoperative endoscopy was associated with a lower risk of post-LVAD GIB. Methods: This was a multicenter cohort study of patients who underwent LVAD insertion from 2010-2019 at 3 academic sites. A total of 398 study participants were categorized based on whether they underwent preoperative endoscopy or not. The follow-up period was 1 year and the primary outcome was GIB. Secondary outcomes were severe bleeding and intraprocedural complications. Results: A total of 114 patients experienced GIB within 1 year, with a higher rate in the endoscopy cohort (36.4% vs. 24.8%, P=0.015). After adjusting for covariables, the endoscopy cohort remained at increased risk of GIB (adjusted odds ratio 1.77, 95% confidence interval 1.05-2.976; P=0.032). Severe bleeding was common (47.4%). Arteriovenous malformations (48 cases) and peptic ulcer disease (17 cases) were the most identified sources of GIB. Only 1 minor adverse event occurred during preoperative endoscopy. Conclusions: Our study suggests that pre-LVAD endoscopy is associated with a higher risk of GIB post LVAD, despite controlling for confounders. While this was an observational study and may not have captured all confounders, it appears that endoscopic screening may not be warranted.
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Video 1Use of endoscopic morcellator to assist in removal of stent.
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BACKGROUND/AIMS: We aimed to study the effects of sedation on endoscopic ultrasound-guided tissue acquisition. METHODS: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound-guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS). RESULTS: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234-1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in the ACP group and 66/106 (62.3%) in the CS group, respectively (p=0.0274). In multivariate analysis, the difference in diagnostic yield between the two groups was not significant (aOR, 0.643; 95% CI, 0.356-1.159; p=0.142). A total of 33 adverse events (AEs) were observed. The incidence of AEs was significantly lower in the CS group (5/33 CS vs. 28/33 ACP; OR, 0.281; 95% CI, 0.095-0.833; p=0.022). CONCLUSION: CS provided equivalent technical success and diagnostic yield for malignancy in endoscopic ultrasound-guided tissue acquisition. Increased AEs were associated with anesthesia for the endoscopic ultrasound-guided tissue acquisition.
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http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-skef a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-mikolajczyk an interview with the author.
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BACKGROUND: Chronic pancreatitis (CP) is a chronic, debilitating disorder associated with multiple complications, frequently necessitating hospitalization. The aim of this study was to investigate the longitudinal trends for hospitalization, mean length of stay (LOS), and cost associated with inpatient admissions for CP across the United States. METHODS: Using the Nationwide Inpatient Sample, all hospitalizations between 1997 and 2014 were analyzed. We examined annual data for rate of hospitalization, average LOS and cost for CP inpatient admissions. Trends were described over the surveillance period. RESULTS: Between 1997 and 2014, the number of hospitalizations for patients with a primary discharge diagnosis of CP decreased by 41.5% (P<0.001). While the average LOS decreased by 21.2% from 6.2 days in 1997 to 4.9 days in 2014 (P<0.001), the mean charges for CP-related hospital admissions increased by 308.5% from $12,725 in 1997 to $39,260 (adjusted for inflation) in 2014 (P<0.001). The risk of a discharge for CP significantly increased from 1997-2014 for the 1-17 year age group (relative risk 1.518, 95% confidence interval 1.516-1.520; P<0.0001), while it significantly decreased over time for all the other age groups. CONCLUSIONS: Although it is reassuring that the average LOS has reduced, the cost associated with these hospitalizations has almost tripled. We postulate that the increase in cost is likely attributable to a greater number of studies and/or interventions. In order to deliver more cost-conscious care, further investigation is required into the effect that these additional investigations and interventions have on specific endpoints, including disease-specific and all-cause morbidity and mortality.
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Behçet's disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet's disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time.