Combination Topical Epinephrine and Non-steroidal Inflammatory Drugs in the Prevention of Post-ERCP Pancreatitis: A Systematic Review.

BACKGROUND: The utility of combination rectal NSAID and topical epinephrine (EI) or rectal NSAID and normal saline (SI) sprayed on duodenal papilla in the prevention of post-ERCP pancreatitis (PEP) has been studied but results have been conflicting. AIMS: To evaluate the benefit of using combination prophylaxis in preventing PEP. METHODS: A literature search was performed using Scopus, PubMed/MEDLINE, and Cochrane databases in May 2021. Randomized controlled trials (RCTs) involving adults patients who underwent ERCP and received EI versus SI were eligible for inclusion. The pooled effect was expressed as odds ratio (OR) to assess the rate of PEP, severity of PEP, and specific adverse events. The results were pooled using Reviewer Manager 5.4 software. RESULTS: Six RCTs involving 4016 patients were included in the final analysis. The EI group did not demonstrate any significant benefit over SI group in preventing PEP (OR = 1.00, 95% CI [0.68, 1.45], P = 0.98), irrespective of gender or the epinephrine concentration used. The tests for subgroup differences were not statistically significant with P-values of 0.66 and 0.28, respectively. The addition of topical epinephrine to rectal NSAID did not improve the rate of moderate to severe PEP (OR = 0.94, P = 0.86) or PEP in high-risk patients (OR = 1.14, 95%, P = 0.73). The rates of infection, including cholangitis and sepsis (OR = 0.63, P = 0.07), gastrointestinal bleeding (OR = 1.25, P = 0.56) and procedure-related death (OR = 0.71, P = 0.59) were similar between both groups. CONCLUSION: The addition of topical epinephrine did not demonstrate any benefit over rectal NSAID alone in preventing PEP or reducing other procedure-related adverse events.

Endoscopic ultrasound-guided portal pressure gradient with liver biopsy: 6 years of endo-hepatology in practice.

BACKGROUND AND AIM: The portal pressure gradient (PPG) is a useful predictor of portal hypertension (PH) related complications. We previously showed the feasibility and safety of endoscopic ultrasound guided PPG measurement (EUS-PPG). Now EUS-guided liver biopsy (EUS-bx) has been shown to be a safe and effective alternative to percutaneous or Interventional Radiology-guided liver biopsy for the diagnosis of chronic liver disease (CLD). We aimed to evaluate the correlation between PPG and clinical markers of PH, and assess the feasibility and safety of concomitant, single session EUS-PPG and EUS-bx. METHODS: This was a retrospective study of patients undergoing EUS-PPG for CLD at a single tertiary endoscopy center between February 2014 and March 2020. EUS-PPG was performed using a 25-gauge needle and compact manometer. Data analysis was performed with SAS version 9.4. RESULTS: Eighty-three patients underwent EUS-PPG with 100% technical success. The mean PPG was 7.06 mmHg (SD 6.09, range 0-27.3). PPG was higher in patients with (vs without) clinical features of cirrhosis (9.46 vs 3.61 mmHg, P < 0.0001), esophageal or gastric varices (13.88 vs 4.34 mmHg, P < 0.0001), and thrombocytopenia (9.25 vs 4.71 mmHg, P = 0.0022). In the 71 patients (85.5%) who underwent EUS-bx, 70 (98.6%) specimens were deemed adequate by the pathologist for histologic diagnosis. There were no early or late major adverse events. CONCLUSION: EUS-PPG correlates well with clinical markers of PH. EUS-bx can be performed safely during the same session as EUS-PPG, providing a comprehensive endoscopic evaluation of the patient with CLD.

A phase Ib feasibility trial of response adapted neoadjuvant therapy in gastric cancer (RANT-GC).

Current guidelines recommend neoadjuvant (NAC) and/or adjuvant chemotherapy for locally advanced gastric cancers (LAGCs). However, the choice and duration of NAC regimen is standardized, rather than personalized to biologic response, despite the availability of several different classes of agents for the treatment of gastric cancer (GC). The current trial will use a tumor-informed ctDNA assay (Signatera™) and monitor response to NAC. Based on ctDNA kinetics, the treatment regimen is modified. This is a prospective single center, single-arm, open-label study in clinical stage IB-III GC. ctDNA is measured at baseline and repeated every 8 weeks. Imaging is performed at the same intervals. The primary end point is the feasibility of this approach, defined as percentage of patients completing gastrectomy.

Endoscopic Ultrasound-Guided Porto-systemic Pressure Gradient Measurement Correlates with Histological Hepatic Fibrosis.

BACKGROUND AND AIMS: Endoscopic ultrasound is a novel diagnostic approach to chronic liver diseases (CLDs), and EUS-guided porto-systemic pressure gradient measurement (EUS-PPG) is an important expansion with a well-developed technique. However, the clinical value and applicability of EUS-PPG measurement in predicting histologically advanced hepatic fibrosis remain unknown. METHODS: This was a single-center retrospective study on patients with various CLDs undergoing EUS-PPG and EUS-guided liver biopsy (EUS-bx) to assess if EUS-PPG measurements correlate with histological fibrosis stage and various surrogate markers for severity of CLDs and its safety. Cases with EUS-PPG were identified at the University of California Irvine, a tertiary endoscopy center, between January 2014 and March 2020. RESULTS: In 64 patients, the mean age was 57.5; 40 (62.5%), males; mean Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, 5.9 and 10.4, respectively. The procedure success rate was 100%. Twenty-nine (45.3%) had EUS-PPG ≥ 5 mmHg that was associated with clinical cirrhosis (p < 0.0001), clinical portal hypertension (p = 0.002), hepatic decompensation (p = 0.013), MELD-Na > 10 (p = 0.036), PLTs ≤ 120 × 109/L (p = 0.001), INR ≥ 1.05 (p = 0.007), presence of EV, GV, or PHG (p < 0.0001), biopsy-proven fibrosis stage ≥ 3 (p = 0.002), APRI > 2 (p = 0.001), and FIB-4 > 3.25 (p = 0.001). Multivariable analysis confirmed that EUS-PPG ≥ 5 mmHg was significantly associated with liver biopsy-proven fibrosis stage ≥ 3 (LR 27.0, 95% CI = 1.653-360.597, p = 0.004), independent of C-cirrhosis, C-PHTN, thrombocytopenia, splenomegaly, and APRI score > 2, and FIB-4 score > 3.25. There were no serious complications related to EUS-PPG procedures. CONCLUSIONS: EUS-PPG measurements provide excellent correlation with histological hepatic fibrosis stage and various clinical, laboratory, endoscopic and imaging variables indicative of advanced liver disease without serious adverse events.

Single-Day Low-Residue Diet Prior to Colonoscopy Demonstrates Improved Bowel Preparation Quality and Patient Tolerance over Clear Liquid Diet: A Randomized, Single-Blinded, Dual-Center Trial.

BACKGROUND AND AIMS: Patients often refer to bowel preparation and associated dietary restrictions as the greatest deterrents to having a colonoscopy completed or performed. Large studies comparing a low-residue diet (LRD) and a clear liquid diet (CLD) are still limited. The aim of this study is to compare LRD and CLD with regard to bowel preparation quality, tolerance, and satisfaction among a diverse patient population. METHODS: This study is a dual-center, randomized, single-blinded, prospective trial involving adult patients undergoing outpatient colonoscopy at the University of California Irvine Medical Center and an affiliated Veterans Administration hospital. Patients were randomized to consume either a CLD or a planned LRD for the full day prior to colonoscopy. Both groups consumed 4L split-dosed PEG-ELS. The adequacy of bowel preparation was evaluated using the Boston Bowel Preparation Score (BBPS). Adequate preparation was defined as a BBPS ≥ 6 with no individual segment less than a score of 2. Hunger and fatigue pre - and post-procedure were graded on a ten-point scale. Nausea, vomiting, bloating, abdominal cramping, overall discomfort, satisfaction with the diet, willingness to repeat the same preparation and overall experience were assessed. RESULTS: A total of 195 subjects who underwent colonoscopy from October 2014 to October 2017 were included. The mean BBPS for the LRD and CLD groups was 8.38 and 7.93, respectively (p = 0.1). There was a significantly higher number of adequate preparations in the LRD group compared to CLD (p = 0.05). Evening hunger scores just before starting the bowel preparation were significantly lower in the LRD than the CLD group, 2.81 versus 5.97, respectively (p = 0.006). Subjects in the LRD group showed significantly less nausea (p = 0.047) and bloating (p = 0.04). Symptom scores for vomiting, abdominal cramping, and overall discomfort were similar between the groups. Satisfaction with diet was significantly higher in the LRD group than CLD, 72% versus 37.66%, respectively (p < 0.001). The overall colonoscopy experience and the satisfaction with the preparation itself were also better reported in the LRD group (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: This study, which included a diverse group of patients, demonstrated that patients using a LRD before colonoscopy achieve a bowel preparation quality that is superior to patients on a CLD restriction. This study shows that a low-residue diet improves patient satisfaction and results in significantly better tolerability of bowel preparation. As a less restrictive dietary regimen, the low-residue diet may help improve patient participation in colorectal cancer screening programs.

Per-Oral Endoscopic Myotomy for Esophagogastric Junction Outflow Obstruction: A Multicenter Pilot Study.

Esophagogastric junction outflow obstruction (EGJOO) is a rare but increasingly recognized diagnosis as described by The Chicago Classification of Esophageal Motility Disorders version 3.0 (version 3.0).1 On high-resolution manometry (HRM), EGJOO is characterized by increased integrated relaxation pressure (IRP) of the lower esophageal sphincter (LES), yet with some preserved esophageal peristalsis.2-4 Little consensus exists on the preferred therapeutic approach.3 Although conceptually per-oral endoscopic myotomy (POEM) should address the measurable dysfunction in the LES, few data exist to support this.5 Thus, we aimed to evaluate the safety and efficacy of POEM for the treatment of symptomatic EGJOO.

Underwater versus conventional EMR for colorectal polyps: systematic review and meta-analysis.

BACKGROUND AND AIMS: Underwater EMR (UEMR) has emerged as an attractive alternative to conventional EMR (CEMR) for the resection of colorectal polyps. The purpose of this systematic review and meta-analysis was to compare UEMR and CEMR for the resection of colorectal polyps with respect to efficacy and safety. METHODS: A literature search was performed across multiple databases, including MEDLINE/PubMed, The Cochrane Library, CINAHL, Google Scholar, and Scopus, for studies that were published until May 2020. Only studies that compared the resection of colorectal polyps using UEMR with CEMR were included. Outcomes examined included rates of en bloc resection, recurrence, postprocedure bleeding, perforation, and resection time. RESULTS: Seven studies totaling 1237 polyps were included: 614 polyps were resected with UEMR and 623 polyps with CEMR. UEMR was associated with a significant increase in the rate of overall en bloc resection (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.42-2.39; P < .001; I2 = 38%), with subgroup analysis showing a significant increase in the rates of en bloc resection in polyps ≥20 mm (OR, 1.51; 95% CI, 1.06-2.14; P = .02; I2 = 44%) but not in polyps <20 mm (OR, 1.07; 95% CI, .65-1.76; P = .80; I2 = 27%), and with a significant reduction in the rate of recurrence (OR, .30; 95% CI, .16-.57; P = .0002; I2 = 0%), again driven by improvements in polyps ≥20 mm. There was no significant difference in postprocedure bleeding (OR, 1.11; 95% CI, .57-2.17; P = .76; I2 = 0%) or perforation (OR, .72; 95% CI, .19-2.83; P = .64; I2 = 0%). CONCLUSIONS: The results of this systematic review and meta-analysis demonstrate that UEMR is a safe and efficacious alternative to CEMR. With appropriate training, UEMR may be strongly considered as a first-line option for resection of colorectal polyps.

A Polyp Worth Removing: A Paradigm for Measuring Colonoscopy Quality and Performance of Novel Technologies for Polyp Detection.

Leaving no significant polyp behind while avoiding risks due to unnecessary resections is a commonsense strategy to safely and effectively prevent colorectal cancer (CRC) with colonoscopy. It also alludes to polyps worth removing and, therefore, worth finding. The majority of "worthy" precancerous polyps are adenomas, which for over 2 decades, have received the most attention in performance research and metrics. Consequently, the detection rate of adenomas is currently the only validated, outcome-based measure of colonoscopy demonstrated to correlate with reduced risk of postcolonoscopy CRC. However, a third or more of postcolonoscopy CRCs originate from sessile serrated polyps (SSPs), which are notoriously difficult to find, diagnose and completely resect. Among serrated polyps, the agreement among pathologists differentiating SSPs from non-neoplastic hyperplastic polyps is moderate at best. This lack of ground truth precludes SSPs from consideration in primary metrics of colonoscopy quality or performance of novel polyp detection technologies. By instead leveraging the distinct endoscopic and clinical features of serrated polyps, including those considered important due to proximal location and larger size, clinically significant serrated polyps represent serrated polyps worth removing, enriched with subtle precancerous SSPs. With the explosion of technologies to assist polyp detection, now is the time to broaden benchmarks to include clinically significant serrated polypss alongside adenomas, a measure that is relevant both for assessing the performance of endoscopists, and for assessing new polyp detection technologies.

Comparison of Two Specialized Histology Needles for Endoscopic Ultrasound (EUS)-Guided Liver Biopsy: A Pilot Study.

BACKGROUND: EUS-guided liver biopsy (EUS-LB) has been shown to be a safe and effective alternative to percutaneous liver biopsy. The optimal needle device and technique for EUS-LB is still evolving. The aim of this study was to compare the efficacy of two second-generation 19G fine-needle biopsy (FNB) (Franseen- and Fork-tip) devices for EUS-LB. METHODS: This is a repeated-measure crossover study with a prospectively maintained cohort of patients. We performed EUS-LB with a one-pass and single-actuation method using two 19G FNB needles in 22 consecutive patients between 10/2018 and 9/2019. Patients were randomized to left vs right liver lobes to be biopsied as well as the needle sequence. The specimens obtained were evaluated for adequacy for histologic diagnosis. The primary outcome was number of complete portal tracts (CPTs), post-fix aggregate, and longest specimen length. Secondary outcomes were prefix aggregate specimen length and the specimen adequacy judged by two expert pathologists. RESULTS: A total of 44 liver biopsies were performed in 22 patients. The CPTs were higher in the Franseen-tip needle group compared to the Fork-tip needle group (14.4 vs 9.5, p = 0.043). Post-fix aggregate specimen length (44.9 mm vs 34.6 mm, p = 0.097), the post-fix longest specimen length (19.9 mm vs 13.7 mm, p = 0.175), and prefix aggregate specimen length (51.7 mm vs 45 mm, p = 0.265) were not significantly different. Both needles showed similarly high histologic adequacy (100% vs 95.5%, p = 0.312). Interestingly, the right of the liver showed higher yield of CPTs with both needles (Franseen, 16.2 vs. 12.8, p = 0.003, the Fork-tip, 12.8 vs. 7.0, p < 0.0001). CONCLUSION: EUS-guided liver biopsy using the 19G Franseen-tip needle may provide more CPTs than 19G Fork-tip needle on a single-pass, single-actuation comparison.

Oral IBGard™ Before Colonoscopy: A Single-Center Double-Blinded, Randomized, Placebo-Controlled Trial.

BACKGROUND: Peppermint oil is well known to inhibit smooth muscle contractions, and its topical administration during colonoscopy is reported to reduce colonic spasms. AIMS: We aimed to assess whether oral administration of IBGard™, a sustained-release peppermint oil formulation, before colonoscopy reduces spasms and improves adenoma detection rate (ADR).  METHODS: We performed a single-center randomized, double-blinded, placebo-controlled trial. Patients undergoing screening or surveillance colonoscopies were randomized to receive IBGard™ or placebo. The endoscopist graded spasms during insertion, inspection, and polypectomy. Bowel preparation, procedure time, and time of drug administration were documented. Statistical analysis was performed using the Student's t test and Wilcoxon rank-sum test. RESULTS: There was no significant difference in baseline characteristics or dose-timing distribution between IBGard™ and placebo groups. Similarly, there was no difference in ADR (IBGard™ = 47.8%, placebo = 43.1%, p = 0.51), intubation spasm score (1.23 vs 1.2, p = 0.9), withdrawal spasm score (1.3 vs 1.23, p = 0.72), or polypectomy spasm score (0.52 vs 0.46, p = 0.69). Limiting the analysis to patients who received the drug more than 60 min prior to the start of the procedure did not produce any significant differences in these endpoints. CONCLUSIONS: This randomized controlled trial failed to show benefit of orally administered IBGard™ prior to colonoscopy on the presence of colonic spasms or ADR. Because of its low barrier to widespread adoption, the use of appropriately formulated and timed oral peppermint oil warrants further study to determine its efficacy in reducing colonic spasms and improving colonoscopy quality.

Artificial intelligence using convolutional neural networks for real-time detection of early esophageal neoplasia in Barrett's esophagus (with video).

BACKGROUND AND AIMS: The visual detection of early esophageal neoplasia (high-grade dysplasia and T1 cancer) in Barrett's esophagus (BE) with white-light and virtual chromoendoscopy still remains challenging. The aim of this study was to assess whether a convolutional neural artificial intelligence network can aid in the recognition of early esophageal neoplasia in BE. METHODS: Nine hundred sixteen images from 65 patients of histology-proven early esophageal neoplasia in BE containing high-grade dysplasia or T1 cancer were collected. The area of neoplasia was masked using image annotation software. Nine hundred nineteen control images were collected of BE without high-grade dysplasia. A convolutional neural network (CNN) algorithm was pretrained on ImageNet and then fine-tuned with the goal of providing the correct binary classification of "dysplastic" or "nondysplastic." We developed an object detection algorithm that drew localization boxes around regions classified as dysplasia. RESULTS: The CNN analyzed 458 test images (225 dysplasia and 233 nondysplasia) and correctly detected early neoplasia with sensitivity of 96.4%, specificity of 94.2%, and accuracy of 95.4%. With regard to the object detection algorithm for all images in the validation set, the system was able to achieve a mean average precision of .7533 at an intersection over union of .3 CONCLUSIONS: In this pilot study, our artificial intelligence model was able to detect early esophageal neoplasia in BE images with high accuracy. In addition, the object detection algorithm was able to draw a localization box around the areas of dysplasia with high precision and at a speed that allows for real-time implementation.

EUS-guided portal pressure gradient measurement with a simple novel device: a human pilot study.

BACKGROUND AND AIMS: Portal hypertension (PH) is a serious adverse event of liver cirrhosis. The hepatic venous pressure gradient or portal pressure gradient (PPG) accurately reflects the degree of PH and is the single best prognostic indicator in liver disease. This is usually obtained by interventional radiology (IR), although it is not routinely performed. Recently, we developed a simple novel technique for EUS-guided PPG measurement (PPGM). Our animal studies showed excellent correlation between EUS-PPGM and IR-PPGM. We present the first human pilot study of EUS-PPGM in patients with liver disease. METHODS: EUS-PPGM was performed by experienced endosonographers using a linear echoendoscope, a 25-gauge fine-needle aspiration needle, and a novel compact manometer. The portal vein and hepatic vein (or inferior vena cava) were targeted using a transgastric-transduodenal approach. Clinical parameters of PH were evaluated in each patient. Feasibility was defined as successful PPGM in each patient. Safety was based on adverse events captured in a postprocedural interview. RESULTS: Twenty-eight patients underwent EUS-PPGM with 100% technical success and no adverse events. PPG ranged from 1.5 to 19 mm Hg and had excellent correlation with clinical parameters of portal hypertension including the presence of varices (P = .0002), PH gastropathy (P = .007), and thrombocytopenia (P = .036). PPG was increased in patients with high clinical evidence of cirrhosis (P = .005). CONCLUSION: This novel technique of EUS-PPGM using a 25-gauge needle and compact manometer is feasible and appears safe. Given the availability of EUS and the simplicity of the manometry setup, EUS-guided PPG may represent a promising breakthrough for procuring indispensable information in the management of patients with liver disease.

EUS-guided portal pressure gradient measurement with a novel 25-gauge needle device versus standard transjugular approach: a comparison animal study.

BACKGROUND AND AIMS: Portal hypertension (PH) is a serious adverse event of liver cirrhosis. The hepatic venous pressure gradient (HVPG) accurately reflects the degree of PH and is the single best prognostic factor in liver disease. Currently, portal pressure gradient (PPG) measurement is performed at interventional radiology (IR) with a standard transjugular approach requiring radiation and intravenous contrast. The aim of this study was to develop a novel EUS-guided system using a 25G FNA needle and compact manometer to directly measure PPG and to evaluate its performance and clinical feasibility. METHODS: Experiments were performed in 3 swine that were under general anesthesia. Manometry was performed in venous (baseline and PH) and arterial (aorta) systems. The PH model was created by rapid Dextran-40 infusion peripherally. Under EUS guidance a 25G FNA needle with attached manometer was used to puncture (transgastric-transhepatic approach) and measure pressures in the portal vein, right hepatic vein (RHV), inferior vena cava (IVC), and aorta. With the IR approach, RHV (free and wedged), IVC, and aorta pressure were measured with an occlusion balloon. Pressure correlation was divided into 3 groups; low pressure (baseline), medium pressure (noncirrhotic portal hypertensive model), and high pressure (arterial). Correlation between the 2 methods of measurement was charted in scatter plots, and the Pearson's correlation coefficient (R) was calculated. RESULTS: EUS identification, access, and manometry was successful in all targeted vessels. There was excellent correlation (R, .985-.99) between EUS and IR methods in all pressure ranges. No adverse event occurred. CONCLUSIONS: This novel technique of EUS-PPG measurement using a 25G needle and novel manometer was feasible and demonstrated excellent correlation with the standard transjugular method throughout low, medium, and high pressure ranges.

The PEG-Pedi-PEG technique: a novel method for percutaneous endoscopic gastrojejunostomy tube placement (with video).

BACKGROUND AND AIMS: When PEG tube feeding is complicated by anatomic obstruction, dysmotility, or aspiration, a need arises for feeding beyond the pylorus. The currently available percutaneous gastrojejunostomy (PEG-J) kits have issues with the jejunal extension portion migrating back into the stomach. The aim of this study was to evaluate the feasibility and safety of a novel technique that creates PEG-J tubes by combining an adult percutaneous gastrostomy (PEG) tube with a pediatric PEG tube, the PEG-Pedi-PEG procedure. METHODS: This was a retrospective study at a single tertiary care center. The main outcome measures were success of placement, rate of retrograde tube migration, early (<24 h after procedure was performed) and late (>24 h after procedure was performed) adverse events. RESULTS: Seventeen patients underwent PEG-Pedi-PEG procedures during the study period. Technical success was achieved in all patients (100%). The retrograde migration rate of the jejunal extension tube was 0%. Early adverse events included peristomal pain in 1 patient. Late adverse events included inadvertent tube removal (3 patients), diarrhea (1 patient), prolonged ileus/gastroparesis (1 patient), and tube occlusion (1 patient). Mean follow-up was 290 days. CONCLUSIONS: The PEG-Pedi-PEG procedure is a novel endoscopic technique to facilitate post-pyloric feeding because the pediatric PEG bumper may act like a sail in the small bowel, with peristalsis pushing the bumper distally and thus decreasing the possibility of migration back into the stomach. This study demonstrated excellent technical success, no retrograde migration, and a low rate of adverse events.

Role of serial EUS-guided FNA on pancreatic cystic neoplasms: a retrospective analysis of repeat carcinoembryonic antigen measurements.

BACKGROUND AND AIMS: Pancreatic cystic neoplasms (PCNs) often need interval surveillance, including repeat EUS, but the role of repeat FNA with fluid analysis is poorly defined. The aim of this analysis is to evaluate the potential clinical significance of serial carcinoembryonic antigen (CEA) measurements by EUS-guided FNA (EUS-FNA) in the surveillance for PCNs. PATIENTS: Patients who underwent EUS-FNA for PCNs were studied retrospectively. EUS-FNA findings were compared between index and prior procedures among patients who underwent repeat EUS-FNA. RESULTS: A total of 400 patients with PCNs underwent EUS-FNA. Eighty-seven of those patients had prior EUS-FNA with cyst fluid analysis. Patients with repeat FNA were significantly more likely to have multiple cysts (57% vs 41%; P = .008), multilocular cysts (75% vs 62%; P = .042), connection to pancreatic duct (33% vs 18%; P = .005), and higher initial CEA levels (94.8 vs 25.6 ng/mL; P = .003) compared with patients who had only a single FNA. A comparison of prior and index FNAs did not show significant differences in EUS or cyst fluid analysis findings. After log transformation, the association between CEA level at prior and index FNA was moderate (R2 = 0.626; P < .001), but cystic fluid CEA classification with a cutoff value of 192 ng/mL changed in 17 patients (20%), without significant changes in EUS findings. CONCLUSIONS: Repeat surveillance EUS-FNA resulted in stable CEA levels in the majority of patients, with spurious fluctuations of CEA in approximately 20% of patients. These data call into question any clinical significance attributed to an isolated interval rise in CEA level, especially in light of a stable EUS examination.

In vivo imaging of porcine gastric enteric nervous system using confocal laser endomicroscopy &molecular neuronal probe.

BACKGROUND AND AIM: The gastric enteric nervous system (GENS) is organized into the submucosal plexus and the myenteric plexus that regulate muscle activity and mucosal functions, respectively. A non-invasive, in vivo visualization of GENS was not possible until recent introduction of needle-based confocal laser endomicroscopy (nCLE). Our aim was to determine the feasibility of in vivo visualization of GENS in the porcine stomach using endoscopic ultrasound (EUS) guided nCLE and local injection of molecular neuronal probe NeuroTrace. METHODS: In anesthetized pigs during endoscopy, NeuroTrace was injected into the submucosa and muscularis propria of distal, and proximal stomach under EUS guidance and nCLE imaging was performed using the Cellvizio AQ Flex probe. After euthanasia, transmural gastric specimens from the areas of NeuroTrace injection were obtained for histology. We performed quantitative analysis of nCLE images recorded during in vivo studies: histologic evaluation of unstained specimens under fluorescence microscope for NeuroTrace localization. We also performed immunostaining of these specimens for nerve growth factor (NGF). In in vitro studies, we examined the uptake of NeuroTrace by glial cells. RESULTS: The nCLE imaging successfully visualized neuronal cells and nerve fibers in distinctive image patterns. Fluorescence microscopy of mucosal sections showed that in vivo-injected NeuroTrace was retained in GENS components. NGF was strongly expressed in neural and glial cells, and the pattern of NGF staining was similar to that of NeuroTrace staining. CONCLUSIONS: This study demonstrates for the first time that combined use of EUS-guided nCLE and NeuroTrace is capable to visualize GENS.

Diagnosis of pancreatic cysts: EUS-guided, through-the-needle confocal laser-induced endomicroscopy and cystoscopy trial: DETECT study.

BACKGROUND: The diagnosis of pancreatic cystic neoplasms (PCNs), which now depends on morphology, cytology, and fluid analysis, is still challenging. A novel confocal laser endomicroscopy probe that can be inserted through a 19-gauge FNA needle allows needle-based confocal laser endomicroscopy (nCLE), and the feasibility of nCLE has been reported in PCNs. The combination of cystoscopy by using a through-the-needle fiberoptic probe in combination with nCLE under EUS guidance may improve the diagnosis of PCNs. OBJECTIVE: To assess the feasibility, safety, and diagnostic yield of the combination of cystoscopy and nCLE in the clinical diagnosis of PCNs. DESIGN: A prospective feasibility study. SETTING: An academic tertiary referral center. PATIENTS: Thirty patients with PCNs. INTERVENTIONS: EUS-guided dual through-the-needle imaging (cystoscopy and nCLE) for PCNs. MAIN OUTCOME MEASUREMENTS: Technical feasibility and safety. Associations of cystoscopy and nCLE findings with clinical diagnosis of PCNs. RESULTS: The procedure was technically successful with the exception of 1 probe exchange failure. In 2 patients (7%), postprocedure pancreatitis developed. Specific features associated with the clinical diagnosis of mucinous cysts were identified: mucin on cystoscopy and papillary projections and dark rings on nCLE. The sensitivity of cystoscopy was 90% (9/10), and that of nCLE was 80% (8/10), and the combination was 100% (10/10) in 18 high-certainty patients. LIMITATIONS: A single-center study and lack of complete pathologic correlation. CONCLUSION: The combination of dual through-the-needle imaging (cystoscopy and nCLE) of pancreatic cysts appears to have strong concordance with the clinical diagnosis of PCN. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01447238.).