Clinical predictors of significant findings on EUS for the evaluation of incidental common bile duct dilation.

BACKGROUND AND AIMS: Although EUS is highly accurate for the evaluation of common bile duct (CBD) dilation, the yield of EUS in patients with incidental CBD dilation is unclear. METHODS: Serial patients undergoing EUS for incidental, dilated CBD (per radiologist, minimum of >6 mm objectively) from 2 academic medical centers without active pancreaticobiliary disease or significantly elevated liver function test results were evaluated. Multivariable logistic regression identified predictors of EUS with significant findings and a novel prediction model was derived from one center, internally validated with bootstrapping, and externally validated at the second center. RESULTS: Of 375 patients evaluated, 31 (8.3%) had significant findings, including 26 choledocholithiasis, 1 ampullary adenoma, and 1 pancreatic mass. Predictors of significant findings with EUS included age of ≥70 years (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-10.0), non-biliary-type abdominal pain without chronic pain (OR, 6.1; 95% CI, 2.3-17.3), CBD diameter of ≥15 mm or ≥17 mm with cholecystectomy (OR, 6.9; 95% CI, 2.7-18.7), and prior ERCP (OR, 6.8; 95% CI, 2.1-22.5). A point-based novel clinical prediction model was created: age of ≥70 years = 1, non-biliary-type abdominal pain without chronic pain = 2, prior ERCP = 2, and CBD dilation = 2. A score of <1 had 93% (development) and 100% (validation) sensitivity and predicted a <2% chance of having a significant finding in both cohorts while excluding the need for EUS in ∼30% of both cohorts. Conversely, a score of ≥4 was >90% specific for the presence of significant pathology. CONCLUSIONS: Less than 10% of patients undergoing EUS for incidental CBD dilation had pathologic findings. This novel, externally validated, clinical prediction model may reduce low-yield, invasive evaluation in nearly one-third of patients.

Through-the-scope clip retention rates and performance in a porcine model.

Background and study aims Limited comparative data exist to guide optimal through-the-scope (TTS) clip selection. The aim of this study was to compare the efficacy, retention, and safety of three industry-leading TTS clips on tissue that mimics common clinical scenarios. Methods A survival study involving six domestic pigs was undertaken. Three commonly used clip models were selected: Assurance (STERIS, Mentor, Ohio, United States), Resolution (Boston Scientific, Boston, Massachusetts, United States), and SureClip (Micro-Tech, Ann Arbor, Michigan, United States). To mimic clinical practice, the following scenarios were assessed: (1) normal mucosa; (2) cold snare resection; and (3) hot mucosal resection simulating fibrotic ulcers. Deployment of clips was randomized to target sites. Repeat endoscopy was performed 2 weeks following placement. Endoscopists rated the ease of use of clip placement on a Likert scale of 1 to 5. Results Fifty-four clips (18 Assurance, 18 Resolution, and 18 SureClip) were placed in six pigs. Mucosal healing was noted at all sites on follow up. Overall retention was nine of 18 (50.0%) SureClip, 10 of 18 (55.6%) Assurance, and 13 of 18 (72.2%) Resolution ( P =0.369). There was no difference in clip retention on normal and cold snare resection sites; however, clip retention was significantly higher for Resolution clips on fibrotic ulcers (50.0% versus 0% for Assurance and 0% SureClip, P =0.03). No adverse events were reported. Ease of use was equivalent across all models. Conclusions All clips were equivalent in efficacy and safety with successful clip deployment and mucosal healing. Overall retention rate was low for fibrotic tissue, with an improved retention rate observed with Resolution clips.

Prospective Study Assessing Impact of Ethylene Oxide Sterilization on Endoscopic Ultrasound Image Quality.

BACKGROUND & AIMS: Duodenoscope-associated transmission of infections has raised questions about efficacy of endoscope reprocessing using high-level disinfection (HLD). Although ethylene oxide (ETO) gas sterilization is effective in eradicating microbes, the impact of ETO on endoscopic ultrasound (EUS) imaging equipment remains unknown. In this study, we aimed to compare the changes in EUS image quality associated with HLD vs HLD followed by ETO sterilization. METHODS: Four new EUS instruments were assigned to 2 groups: Group 1 (HLD) and Group 2 (HLD + ETO). The echoendoscopes were assessed at baseline, monthly for 6 months, and once every 3 to 4 months thereafter, for a total of 12 time points. At each time point, review of EUS video and still image quality was performed by an expert panel of reviewers along with phantom-based objective testing. Linear mixed effects models were used to assess whether the modality of reprocessing impacted image and video quality. RESULTS: For clinical testing, mixed linear models showed minimal quantitative differences in linear analog score (P = .04; estimated change, 3.12; scale, 0-100) and overall image quality value (P = .007; estimated change, -0.12; scale, 1-5) favoring ETO but not for rank value (P = .06). On phantom testing, maximum depth of penetration was lower for ETO endoscopes (P < .001; change in depth, 0.49 cm). CONCLUSIONS: In this prospective study, expert review and phantom-based testing demonstrated minimal differences in image quality between echoendoscopes reprocessed using HLD vs ETO + HLD over 2 years of clinical use. Further studies are warranted to assess the long-term clinical impact of these findings. In the interim, these results support use of ETO sterilization of EUS instruments if deemed clinically necessary.

Colorectal Cancer and Polyp Detection Using a New Preparation-Free, Colon-Scan Capsule: A Pilot Study of Safety and Patient Satisfaction.

BACKGROUND: Current strategies to prevent colorectal cancer (CRC) vary considerably regarding safety, invasiveness, and patient satisfaction. A known deterrent for patients is the required bowel cleansing for colonoscopy. A new colon-scan capsule system is a unique preparation-free approach that provides structural information on colonic mucosa intended for detection of colorectal polyps and masses. AIMS: The aim of this study was to determine safety and patient satisfaction with the colon-scan capsule. METHODS: Prospective single-arm pilot study conducted at two tertiary care centers. Patients with a pre-scheduled colonoscopy for CRC screening or surveillance were included. Patients participating in this study underwent the colon-scan capsule and colonoscopy. Safety was defined by the occurrence of procedure or device-related adverse events. Satisfaction was based on survey questionnaires using a scoring system 1 (strongly disagree) to 5 (strongly agree). Patient satisfaction with the colon-scan capsule was compared to colonoscopy. RESULTS: Forty patients were included (52.9 [5.7] years; 64.1% females). There were no serious adverse events and no occurrences of capsule retention. The most common (12.5%) complaint was self-limiting abdominal cramping. Satisfaction questionnaires were completed by more than 87% of patients, with patients likely to recommend the capsule (score 4.1 [1.03]) compared to colonoscopy (score 2.8 [1.2]), p = 0.001. CONCLUSIONS: The new prepless colon-scan capsule system is an innovative, minimally invasive technology with demonstrated safety and high patient satisfaction. A multicenter pivotal study is planned to validate the performance, safety, and accuracy of polyp detection using the capsule system in comparison with colonoscopy.

Outcomes of endoscopic ultrasound and endoscopic resection of gastrointestinal subepithelial lesions: a single-center retrospective cohort study.

BACKGROUND: Endoscopic resection (ER) is an emerging therapeutic alternative for subepithelial gastrointestinal lesions (SELs). We aimed to determine whether size, layer of origin, and histology based on endoscopic ultrasound (EUS) and EUS-guided sampling (EUS-GS) influenced the outcomes and selection of patients for ER. METHODS: We performed a retrospective review of patients who underwent EUS, EUS-GS and resection of SELs from 2012-2019. Two pathologists reviewed the histology and layer of origin of all resected specimens, serving as the criterion for EUS accuracy. RESULTS: Seventy-three patients were included, of whom 59 (81%) were gastric SELs. Per EUS, median lesion size was 21 mm (interquartile range 15-32), and 63 (86%) originated from the 4th layer. The overall accuracy of EUS and EUS-GS in predicting the layer of origin and histology was 88% (95% confidence interval [CI] 77-94%) and 96% (95%CI 87-98%), respectively. Based on EUS, 18 (25%) patients were referred for ER, 5 (7%) to laparoscopic-endoscopic cooperative surgery, and 50 (68%) to surgery. Size >20 mm was associated with the type of resection approach (P=0.005), while layer of origin and histology were not (P=0.06 and P=0.09, respectively). When SELs were inaccurately classified (n=4) there were no adverse events or revision of the resection approach. CONCLUSIONS: EUS plays an important role in the outcome of resection approach for SELs, with size significantly influencing the selection for ER. In patients undergoing ER, no revised resections were needed when EUS was inaccurate.

Unique perspective of Muslim patients on gender preference for GI endoscopists: a multicenter survey.

BACKGROUND AND AIMS: Patient preference for a healthcare professional is mediated by physician gender. The primary aim of this study was to assess gender preference for an endoscopist in a cohort of Muslim patients. The secondary aim was to identify factors that influence gender preference. METHODS: This was a multicenter cross-sectional study conducted at 3 tertiary care hospitals in Pakistan. Consecutive patients scheduled for elective outpatient upper endoscopy or colonoscopy were asked to complete a questionnaire immediately before and after the procedure. Data collected included patient demographics, occupation, education level, procedure type, gender preference, and reason for preference. RESULTS: A total of 1078 patients completed the questionnaire (age 43.5 ± 15.8 years; 53.2% men). Upper endoscopy was the most frequent procedure, performed in 84% of patients. Gender preference was expressed by 707 patients (65.6%), of which 511 (72.3%) were willing to wait for an average of 7 days for an endoscopist of the preferred gender. Male patients' preferences (45.1% male endoscopist, 17.1% female endoscopist, 37.8% no preference) differed from female participants' (16.9% male endoscopist, 52.6% female endoscopist, and 30.5% no preference; P < .00001). No education was associated with having a gender preference (odds ratio, .55; 95% confidence interval, .37-.81; P = .003). Reasons for gender preference included religious values and family pressure, which were more frequently expressed by women (P < .0001). CONCLUSIONS: Most Muslims in Pakistan expressed a gender preference, and both female and male patients showed a preference for a same-gender endoscopist. No education was associated with having a gender preference.

Current clinical and research fluid biomarkers to aid risk stratification of pancreatic cystic lesions.

Pancreatic cystic lesions (PCL) are composed of a heterogeneous group of entities that are increasingly diagnosed, generally as incidental findings in asymptomatic patients. In conjunction with this growing incidence, the potential for malignant transformation of mucin-producing cysts makes PCL a challenging clinical conundrum for the clinician, patient, and healthcare system. Cyst characterization based on morphology is often difficult and inaccurate. Therefore, several intracystic fluid biomarkers have been evaluated as ancillary testing to enhance the difficult balance between sparing a patient from an unnecessary high-risk pancreatic surgery and missing the opportunity to prevent or diagnose pancreatic adenocarcinoma at an early disease stage. There are two questions that are key to guide the care of patients with PCL: 1) is it a non-mucinous cyst that does not require any follow-up? and 2) if mucinous, does the cyst harbor advanced neoplasia (high-grade dysplasia or invasive carcinoma) that requires surgical resection, or is it a low-risk lesion that will benefit from a surveillance program? The purpose of this review is to give a general and practical overview of the different cyst fluid biomarkers that have been studied to address these specific questions, from classic biochemical markers such as carcinoembryonic antigen to novel genetic and epigenetic markers such as microRNA or intracystic bacterial DNA.

Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study).

OBJECTIVE: Colon capsule endoscopy (CCE) has shown promise for colorectal neoplasia detection compared with optical colonoscopy (OC), but has not been compared with other screening tests in average risk screening patients. DESIGN: Patients 50 to 75 years of age (African Americans, 45-75 years) were randomised to CCE or CT colonography (CTC) and subsequent blinded OC. The primary endpoint was diagnostic yield of polyps ≥6 mm with CCE or CTC. Secondary endpoints included accuracy for size and histology, examination completeness, number/proportion of subjects with polyps and adenomas ≥6 mm and ≥10 mm, subject satisfaction and safety. RESULTS: From 320 enrolled subjects, data from 286 (89.4%) were evaluable. The proportion of subjects with any polyp ≥6 mm confirmed by OC was 31.6% for CCE versus 8.6% for CTC (pPr non-inferiority and superiority=0.999). The diagnostic yield of polyps ≥10 mm was 13.5% with CCE versus 6.3% with CTC (pPr non-inferiority=0.9954). The sensitivity and specificity of CCE for polyps ≥6 mm was 79.2% and 96.3% while that of CTC was 26.8% and 98.9%. The sensitivity and specificity of CCE for polyps ≥10 mm was 85.7% and 98.2% compared with 50% and 99.1% for CTC. Both tests were well tolerated/safe. CONCLUSION: CCE was superior to CTC for detection of polyps ≥6 mm and non-inferior for identification of polyps ≥10 mm. CCE should be considered comparable or superior to CTC as a colorectal neoplasia screening test, although neither test is as effective as OC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov no: NCT02754661.

Application of artificial intelligence using a novel EUS-based convolutional neural network model to identify and distinguish benign and malignant hepatic masses.

BACKGROUND AND AIMS: Detection and characterization of focal liver lesions (FLLs) is key for optimizing treatment for patients who may have a primary hepatic cancer or metastatic disease to the liver. This is the first study to develop an EUS-based convolutional neural network (CNN) model for the purpose of identifying and classifying FLLs. METHODS: A prospective EUS database comprising cases of FLLs visualized and sampled via EUS was reviewed. Relevant still images and videos of liver parenchyma and FLLs were extracted. Patient data were then randomly distributed for the purpose of CNN model training and testing. Once a final model was created, occlusion heatmap analysis was performed to assess the ability of the EUS-CNN model to autonomously identify FLLs. The performance of the EUS-CNN for differentiating benign and malignant FLLs was also analyzed. RESULTS: A total of 210,685 unique EUS images from 256 patients were used to train, validate, and test the CNN model. Occlusion heatmap analyses demonstrated that the EUS-CNN model was successful in autonomously locating FLLs in 92.0% of EUS video assets. When evaluating any random still image extracted from videos or physician-captured images, the CNN model was 90% sensitive and 71% specific (area under the receiver operating characteristic [AUROC], 0.861) for classifying malignant FLLs. When evaluating full-length video assets, the EUS-CNN model was 100% sensitive and 80% specific (AUROC, 0.904) for classifying malignant FLLs. CONCLUSIONS: This study demonstrated the capability of an EUS-CNN model to autonomously identify FLLs and to accurately classify them as either malignant or benign lesions.

Magnet-assist endoscopic augmentation of the lower esophageal sphincter for treatment of gastroesophageal reflux disease: cadaveric and survival studies in a porcine model (with video).

BACKGROUND: Augmentation of the lower esophageal sphincter (LES) is the primary goal of both surgical and endoscopic therapies for gastroesophageal reflux disease (GERD). The feasibility, efficacy, safety, and reversibility of a newly developed endotherapy for GERD using intraluminal magnets referred to as a magnet closure device (MCD) were evaluated. METHODS: This study involved nine cadaveric and six survival pigs. The MCD consisted of a ring neodymium magnet attached to a 2-0 polypropylene suture and suture anchor. The MCD was deployed onto the esophageal wall at the region of the LES using an endoscopic suturing device. Two to three MCDs were placed on opposing walls to induce closure of the esophageal lumen. LES pressures were measured using high-resolution manometry at the index procedure (baseline and immediately post-MCD placement) and at survival endoscopy. Endoscopic removal of the devices was performed followed by necropsy at week 2. RESULTS: MCDs were successfully deployed in all cadaveric (n = 22) and survival animals (n = 12). In cadavers, 20/22 (91%) sutures were full-thickness with no adjacent organ injury. In survival animals, mean LES pressure increased from 8.4 mmHg (baseline) to 32.4 mmHg immediately post-procedure (p < 0.01). No clinically significant adverse events occurred. Repeat endoscopy at two weeks showed intact MCDs in 4/6 (67%) animals with significant increase in median LES pressure (n = 4, 24.0 mmHg versus 7.4 mmHg [baseline], p < 0.05). Endoscopic removal of MCDs was successfully achieved. CONCLUSIONS: Endoscopic augmentation of the LES using a new MCD was feasible, safe and reversible with significantly increased LES pressures recorded. Future studies are needed to enhance durability. These preliminary results on a reversible technique are promising and may represent an attractive alternative to endoluminal GERD therapy.

Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis.

OBJECTIVE: The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time. DESIGN: A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC. RESULTS: From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP). CONCLUSION: The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.

Endoscopic Ultrasound/Fine Needle Aspiration Is Effective for Lymph Node Staging in Patients With Cholangiocarcinoma.

BACKGROUND AND AIMS: Presence of malignant regional lymph nodes (MRLNs) precludes curative oncological resection or liver transplantation for cholangiocarcinoma (CCA). Limited data support the utility of endoscopic ultrasound (EUS)/fine needle aspiration (FNA) for detection of MRLNs in extrahepatic CCA, but there are no data for its role in intrahepatic CCA (iCCA). The aim of this study is to evaluate the staging impact of EUS for CCA, including analysis by subtype. APPROACH AND RESULTS: We identified consecutive patients with CCA who underwent EUS staging at a single tertiary care center from October 2014 to April 2018. Among this cohort, we abstracted clinical demographic, radiographical, procedural, cytopathological, and surgical data. STATA 15 software was used for comparative analysis calculations (StataCorp LP, College Station, TX). The study cohort included 157 patients; 24 (15%), 124 (79%), and 9 (6%) with intrahepatic, perihilar, and distal CCA, respectively. EUS was able to identify regional lymph nodes (RLNs) in a higher percentage of patients compared to cross-sectional imaging (86% vs. 47%; P < 0.001). FNA was performed in 133 (98.5%) patients with RLNs, with a median of three passes per node. EUS-FNA identified MRLN in 27 of 31 (87.1%) patients ultimately found to have MRLNs. For iCCA, EUS detected a higher percentage of RLN compared to cross-sectional imaging (83% vs. 50%; P = 0.048), with MRLNs identified in 4 (17%) patients. Among the entire cohort, identification of at least one MRLN by EUS was associated with lower median survival (353 vs. 1,050 days; P < 0.001) and increased risk of death (hazard ratio = 4.1; P < 0.001). CONCLUSIONS: EUS-FNA is effective for identifying MRLN in patients with CCA, and should be routinely incorporated into staging of all CCA subtypes given the impact of MRLN on prognosis and management decisions.

Clinical impact of celiac ganglia metastasis upon pancreatic ductal adenocarcinoma.

BACKGROUND: Pre-operative staging of pancreatic adenocarcinoma guides clinical decision making. Limited data indicate that metastasis to celiac ganglia (CG) correlates with poor prognosis. We investigated feasibility and safety of endoscopic ultrasound fine needle aspiration (EUS-FNA) detection of CG metastasis and its impact upon tumor stage, resectability, and survival in pancreatic ductal adenocarcinoma (PDAC). PATIENTS: We reviewed our prospectively maintained EUS and cytopathology databases to identify patients with FNA proven CG metastasis in patients with PDAC from 2004 to 2017. Clinical demographics, EUS, CT, MRI, cytopathology, cancer stage, and resectability data were analyzed. Survival of PDAC patients with CG metastasis was compared to the expected survival of PDAC patients of similar stage as reported by the United States National Cancer Database. RESULTS: Twenty-one patients with PDAC [median age 73 (IQR63-78); 14 (67%) female)], had CG metastasis confirmed by cytopathologic assessment. CG metastasis resulted in tumor upstaging relative to other EUS findings and cross sectional imaging findings in 12 (57%) and 15 (71%) patients, and converted cancers from resectable to unresectable relative to EUS and cross sectional imaging in 7 (37%) and 7 (37%) patients, respectively. In patients with PDAC, the survival of patients with CG metastasis was not significantly different from the overall survival (hazard ratio 0.71; 95% confidence interval 0.44, 1.13; p = 0.15). CONCLUSIONS: EUS-FNA may safely identify CG metastases. While CG metastasis upstaged and altered the resectability status among this cohort of patients with PDAC, the survival data with regard to PDAC suggest that this may be misguided.

Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls.

BACKGROUND & AIMS: Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls). METHODS: We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees. RESULTS: We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%). CONCLUSIONS: We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.

Efficacy of Difluoromethylornithine and Aspirin for Treatment of Adenomas and Aberrant Crypt Foci in Patients with Prior Advanced Colorectal Neoplasms.

Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, was shown to act synergistically with a NSAID for chemoprevention of colorectal neoplasia. We determined the efficacy and safety of DFMO plus aspirin for prevention of colorectal adenomas and regression of rectal aberrant crypt foci (ACF) in patients with prior advanced adenomas or cancer. A double-blinded, placebo-controlled trial was performed in 104 subjects (age 46-83) randomized (1:1) to receive daily DFMO (500 mg orally) plus aspirin (325 mg) or matched placebos for one year. All polyps were removed at baseline. Adenoma number (primary endpoint) and rectal ACF (index cluster and total) were evaluated at a one year colonoscopy. ACF were identified by chromoendoscopy. Toxicity was monitored, including audiometry. Eighty-seven subjects were evaluable for adenomas or ACF modulation (n = 62). At one year of treatment, adenomas were detected in 16 (38.1%) subjects in the DFMO plus aspirin arm (n = 42) versus 18 (40.9%) in the placebo arm (n = 44; P = 0.790); advanced adenomas were similar (n = 3/arm). DFMO plus aspirin was associated with a statistically significant reduction in the median number of rectal ACF compared with placebo (P = 0.036). Total rectal ACF burden was also reduced in the treatment versus the placebo arm relative to baseline (74% vs. 45%, P = 0.020). No increase in adverse events, including ototoxicity, was observed in the treatment versus placebo arms. While adenoma recurrence was not significantly reduced by one year of DFMO plus aspirin, the drug combination significantly reduced rectal ACF number consistent with a chemopreventive effect.

An internal magnet traction device reduces procedure time for endoscopic submucosal dissection by expert and non-expert endoscopists: ex vivo study in a porcine colorectal model (with video).

BACKGROUND: Efficacy of an internal magnet traction device (MTD) for gastric endoscopic submucosal dissection (ESD) by an expert endoscopist has been reported. We hypothesized that use of the MTD would enhance the performance of colorectal ESD in a non-expert endoscopist in ESD compared to the conventional technique. Primary aim of this study was to compare procedure times between conventional ESD (C-ESD) and MTD-assisted ESD (MTD-ESD) by expert and non-expert endoscopists in ESD. Secondary aims included rate of en bloc resection, iatrogenic injury, visualization score of the submucosal layer, and endoscopist satisfaction score. METHODS: A total of 56 lesions were created in an ex vivo porcine colorectum. Two endoscopists completed C-ESD (n = 28) and MTD-ESD (n = 28). Lesions measured 3 cm in diameter and were located on either the anterior or posterior colorectal wall. The MTD consisted of a small neodymium magnet and nylon monofilament attached to a through-the-scope clip. The first MTD was deployed on the opposing colorectal wall of the target lesion and a second MTD was then deployed directly onto the distal margin of the lesion. RESULTS: Total procedure time for MTD-ESD was significantly shorter than C-ESD for both expert (median: 15.8 vs. 19.3 min, p < 0.05) and non-expert (median: 21.3 vs. 33.9 min, p < 0.001) endoscopists. All lesions were resected en bloc. There was no iatrogenic muscularis propria injury in the MTD-ESD group. For both the expert and non-expert, scores for MTD-ESD were significantly higher for submucosal layer visualization (p < 0.05) and endoscopist satisfaction (p < 0.001) compared to C-ESD. CONCLUSIONS: Use of the MTD significantly reduced procedure time for both expert and non-expert endoscopists performing ESD. Improving the efficiency, safety, and satisfaction of ESD with such a device particularly for non-expert endoscopists is appealing and could potentially minimize the complexity and duration of the procedure allowing for more widespread use of the technique.

Safety, Diagnostic Accuracy, and Effects of Endoscopic Ultrasound Fine-Needle Aspiration on Detection of Extravascular Migratory Metastases.

BACKGROUND & AIMS: Tumor cells can migrate via diminutive perivascular cuffing to distant sites along blood vessels to form extravascular migratory metastases (EVMM). These metastases usually are identified during surgery or autopsies. We aimed to evaluate the feasibility and safety of endoscopic ultrasound fine-needle aspiration (EUS-FNA) of perivascular soft-tissue cuffs to detect EVMM. We compared findings from EUS with those from noninvasive cross-sectional imaging (reference standard) of patients who underwent EUS-FNA to assess suspected EVMM and studied the effects on pancreatic tumor staging and determination of resectability. METHODS: We performed a retrospective analysis of 253 patients (mean age, 62 ± 12 y) who underwent EUS-FNA of 267 vessels for evaluation of suspected EVMM, from April 2001 through May 2018. EUS findings were compared with those from computed tomography (CT) and magnetic resonance imaging (MRI) as the reference standard. Lesions were considered to be malignant based on cytology analysis of FNA samples, histology analyses of surgical or biopsy specimens, or vascular abnormalities detected by CT or MRI that clearly indicate EVMM. RESULTS: Thirty patients were found to have benign lesions. The remaining 223 patients who had malignancies (166 with pancreatic ductal adenocarcinomas [PDACs]), underwent further analyses. A median of 4 FNAs (range, 1-20 FNAs) were obtained from 4-mm perivascular soft-tissue cuffs (range, 2-20 mm). FNA and cytology analysis showed malignant cells in 163 vessels (69.4%) from 157 patients (70.4%). CT or MRI did not detect EVMM in 44 patients (28%) with malignancies, including 24 patients (24%) with newly diagnosed PDAC. Detection of EVMM by EUS-FNA resulted in upstaging of 15 patients and conversion of 14 patients with PDAC from resectable (based on CT or MRI) to unresectable. No adverse events were reported during a follow-up period of 3.9 months (range, 0-117 mo). CONCLUSIONS: EUS-FNA and cytologic analysis of perivascular soft-tissue cuffs can detect EVMM that were not found in 28% of patients by CT or MRI. Detection of EVMM affects tumor staging and determination of tumor resectability.

Combined Celiac Ganglia and Plexus Neurolysis Shortens Survival, Without Benefit, vs Plexus Neurolysis Alone.

BACKGROUND & AIMS: Pancreatic cancer produces debilitating pain that opioids often ineffectively manage. The suboptimal efficacy of celiac plexus neurolysis (CPN) might result from brief contact of the injectate with celiac ganglia. We compared the effects of endoscopic ultrasound-guided celiac ganglia neurolysis (CGN) vs the effects of CPN on pain, quality of life (QOL), and survival. METHODS: We performed a randomized, double-blind trial of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain; 60 patients (age 66.4±11.6 years; male 66%) received CPN and 50 patients (age 66.8±10.0 years; male 56%) received CGN. Primary outcomes included pain control and QOL at week 12 and survival (overall median and 12 months). Secondary outcomes included morphine response, performance status, secondary neurolytic effects, and adverse events. RESULTS: Rates of pain response at 12 weeks were 46.2% for CGN and 40.4% for CPN (P = .84). There was no significant difference in improvement of QOL between the techniques. The median survival time was significantly shorter for patients receiving CGN (5.59 months) compared to (10.46 months) (hazard ratio for CGN, 1.49; 95% CI, 1.02-2.19; P = .042), particularly for patients with non-metastatic disease (hazard ratio for CGN, 2.95; 95% CI, 1.61-5.45; P < .001). Rates of survival at 12 months were 42% for patients who underwent CPN vs 26% for patients who underwent CGN. The number of adverse events did not differ between techniques. CONCLUSION: In a prospective study of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain, we found CGN to reduce median survival time without improving pain, QOL, or adverse events, compared to CPN. The role of CGN must be therefore be reassessed. Clinicaltrials.gov no: NCT01615653.