Multi-objective Bayesian active learning for MeV-ultrafast electron diffraction.

Ultrafast electron diffraction using MeV energy beams(MeV-UED) has enabled unprecedented scientific opportunities in the study of ultrafast structural dynamics in a variety of gas, liquid and solid state systems. Broad scientific applications usually pose different requirements for electron probe properties. Due to the complex, nonlinear and correlated nature of accelerator systems, electron beam property optimization is a time-taking process and often relies on extensive hand-tuning by experienced human operators. Algorithm based efficient online tuning strategies are highly desired. Here, we demonstrate multi-objective Bayesian active learning for speeding up online beam tuning at the SLAC MeV-UED facility. The multi-objective Bayesian optimization algorithm was used for efficiently searching the parameter space and mapping out the Pareto Fronts which give the trade-offs between key beam properties. Such scheme enables an unprecedented overview of the global behavior of the experimental system and takes a significantly smaller number of measurements compared with traditional methods such as a grid scan. This methodology can be applied in other experimental scenarios that require simultaneously optimizing multiple objectives by explorations in high dimensional, nonlinear and correlated systems.

Development of clinical screening tool for exocrine pancreatic insufficiency in patients with definite chronic pancreatitis.

BACKGROUND/OBJECTIVES: No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP. METHODS: This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric. RESULTS: 274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58 % had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n = 6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation. CONCLUSION: We developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status.

Giant Terahertz Birefringence in an Ultrathin Anisotropic Semimetal.

Manipulating the polarization of light at the nanoscale is key to the development of next-generation optoelectronic devices. This is typically done via waveplates using optically anisotropic crystals, with thicknesses on the order of the wavelength. Here, using a novel ultrafast electron-beam-based technique sensitive to transient near fields at THz frequencies, we observe a giant anisotropy in the linear optical response in the semimetal WTe2 and demonstrate that one can tune the THz polarization using a 50 nm thick film, acting as a broadband wave plate with thickness 3 orders of magnitude smaller than the wavelength. The observed circular deflections of the electron beam are consistent with simulations tracking the trajectory of the electron beam in the near field of the THz pulse. This finding offers a promising approach to enable atomically thin THz polarization control using anisotropic semimetals and defines new approaches for characterizing THz near-field optical response at far-subwavelength length scales.

Outcomes of endoscopic submucosal dissection in cirrhotic patients: First American cohort.

BACKGROUND: Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions, surgical intervention carries a much higher bleeding risk. When such lesions are discovered, endoscopic submucosal dissection (ESD) may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic resection. AIM: To evaluate the outcomes of ESD in patients with cirrhosis. METHODS: Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location, size, and anticoagulation use. Procedural outcomes were compared between groups. RESULTS: A total of 64 Lesions from 59 patients were included (16 cirrhosis, 43 control). There were no differences in patient or lesion characteristics between groups. En bloc and curative resection was achieved in 84.21%, 78.94% of the cirrhosis group and 88.89%, 68.89% of controls, respectively, with no significant differences. Cirrhotic patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding (47.37% vs 20%; P = 0.02). There were otherwise no significant differences in adverse event rates. In the 29 patients with follow up, we found higher rates of recurrence in the cirrhosis group compared to controls (40% vs 5.26%; P = 0.019), however this effect did not persist on multivariable analysis controlling for known confounders. CONCLUSION: ESD may be safe and effective in patients with cirrhosis. Most procedure related outcomes were not significantly different between groups. Intra-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.

Applicability of Child-Turcotte-Pugh Score in Anticipating Post-ERCP Adverse Events in Patients With Cirrhosis: A Systematic Review and Meta-analysis.

Limited objective data exist on the comparison of post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with cirrhosis based on the severity of the disease. We evaluated the effectiveness of the Child-Turcotte-Pugh (CTP) score system in anticipating the risk of post-ERCP complications in patients with cirrhosis. The PubMed, Scopus, Embase, and Cochrane databases were searched from inception through September 2022 to identify studies comparing post-ERCP complications in patients with cirrhosis based on CTP score. Odds ratios (ORs) and their associated 95% CIs were pooled using a random-effect model to calculate effect size. The reference group for analysis was the CTP class C patient group. Seven studies comprising 821 patients who underwent 1068 ERCP procedures were included. The CTP class C patient population exhibited a higher risk of overall post-ERCP adverse events compared with those with class A or B (OR: 2.87, 95% CI: 1.77-4.65, P = 0.00 and OR: 2.02, 95% CI: 1.17-3.51, P = 0.01, respectively). Moreover, CTP class B patients had a significantly higher complication rate than CTP class A patients (OR: 1.62, 95% CI: 1.04-2.53, P = 0.03). However, no statistically significant differences were found in the occurrence of specific types of complications, including bleeding, pancreatitis, cholangitis, perforation, or mortality across the three CTP groups. We demonstrated that the CTP classification system is a reliable predictor of ERCP complications in patients with cirrhosis. Consequently, caution should be exercised when performing ERCP in patients classified as CTP class C.

Improved temporal resolution in ultrafast electron diffraction measurements through THz compression and time-stamping.

We present an experimental demonstration of ultrafast electron diffraction (UED) with THz-driven electron bunch compression and time-stamping that enables UED probes with improved temporal resolution. Through THz-driven longitudinal bunch compression, a compression factor of approximately four is achieved. Moreover, the time-of-arrival jitter between the compressed electron bunch and a pump laser pulse is suppressed by a factor of three. Simultaneously, the THz interaction imparts a transverse spatiotemporal correlation on the electron distribution, which we utilize to further enhance the precision of time-resolved UED measurements. We use this technique to probe single-crystal gold nanofilms and reveal transient oscillations in the THz near fields with a temporal resolution down to 50 fs. These oscillations were previously beyond reach in the absence of THz compression and time-stamping.

LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study.

BACKGROUND: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma. METHODS: LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 µL of LOAd703 at 5 × 1010 (dose 1), 1 × 1011 (dose 2), or 5 × 1011 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants. FINDINGS: Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 [62%] men and eight [38%] women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4-10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 [8%] of 1237 events), lymphopenia (86 [7%] events), hyperglycaemia (70 [6%] events), leukopenia (63 [5%] events), hypertension (62 [5%] events), and hypoalbuminaemia (61 [5%] events). The most common adverse events attributed to LOAd703 were fever (14 [67%] of 21 patients), fatigue (eight [38%]), chills (seven [33%]), and elevated liver enzymes (alanine aminotransferase in five [24%], alkaline phosphatase in four [19%], and aspartate aminotransferase in four [19%]), all of which were grade 1-2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8+ effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25-66) of 18 patients evaluable for activity had an objective response. INTERPRETATION: Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing. FUNDING: Lokon Pharma, the Swedish Cancer Society, and the Swedish Research Council.

The Use of a Self-Assembling Peptide Gel for Stricture Prevention in the Esophagus after Endoscopic Submucosal Dissection: A U.S. Multicenter Prospective Study.

BACKGROUND AND AIMS: Post-operative stricture is serious common adverse event following extensive endoscopic submucosal dissection (ESD) in the esophagus. The self-assembling peptide (SA) gel has been shown to promote tissue healing and re-epithelialization. We aimed to evaluate the effect of the SAP gel for esophageal stricture prevention after ESD. METHODS: Multicenter prospective study of patients who underwent esophageal ESD followed by SAP gel application between March 2022 to December 2023. Patients were included if ESD mucosal defect involved ≥ 50% of the circumference of the esophagus. High-risk cases were defined as mucosal defects ≥75% of the circumference. Stricture was defined as the inability to pass an endoscope ≥8.9 mm in diameter or a narrow-caliber lumen in a patient with symptoms. RESULTS: A total of 43 patients (median age 71 years; 81.4% men) underwent ESD (median resected specimen size 50 mm) during the study period. SAP gel (median 3 mL) was successfully applied in all cases (median time 4 minutes). In aggregate, stricture occurred in 20.9% (9/43) of the cases. Stricture developed in 30.8% of the high-risk cases: 80% (4/5) after circumferential ESD and 19% (4/21) in those with defects ≥75% but <100% of the circumference. All cases of stricture resolved with endoscopic treatment. Three cases (6.9%) of postoperative bleeding occurred and were adequately managed endoscopically. CONCLUSION: We demonstrate that SAP gel application was easy, quick, and associated with a relatively low stricture rate comparable to other prophylactic methods. Additional comparative studies are needed to corroborate these preliminary findings.

The role of transoral incisionless fundoplication (TIF) in the management of gastroesophageal reflux disease (GERD) following peroral endoscopic myotomy (POEM): A pilot, prospective, patient-driven study.

BACKGROUND: Gastroesophageal reflux (GERD) is a concern after peroral endoscopic myotomy (POEM). Transoral incisionless fundoplication (TIF) has been recently described as a possible therapy for post-POEM GERD in case series. METHODS: We prospectively enrolled patients undergoing POEM who agreed to participate in objective post-procedure GERD evaluation. Patients with objective evidence of GERD and suitable anatomy were offered TIF vs. proton pump inhibitor (PPI) only. Patients who underwent TIF were compared to those on PPI-only therapy after follow-up. RESULTS: Of 21 enrolled POEM patients with objective testing, GERD was found in 11 (52%). Of those eligible for TIF, 4 (40%) opted to pursue TIF and were compared to those on PPI-only therapy (n = 6). Three months post-TIF, 75% of patients had discontinued or significantly decreased PPI. There were no adverse events. GERD health-related quality of life scores were low and comparable between TIF (3.75 ± 6.2) and those who remained on PPI-only therapy (4.1 ± 5). CONCLUSION: In this pilot, patient-driven prospective study, 75% of patients with post-POEM GERD undergoing TIF had stopped or significantly reduced PPI use. Post-POEM TIF is safe and effective and may be a viable alternative to PPI for POEM-related GERD; however, future studies should include a control arm and post-intervention pH monitoring.

Feasibility of peroral endoscopic myotomy with a disposable endoscope platform.

Video 1Demonstration of a successful peroral endoscopic myotomy using a novel disposable scope platform.

Efficacy and safety of endoscopic submucosal dissection for colorectal dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND/AIMS: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD). METHODS: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity. RESULTS: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc resection, R0 resection, and curative resection rates were 92.5% (95% confidence interval [CI], 87.9%-95.4%; I2=0%), 81.5% (95% CI, 72.5%-88%; I2=43%), and 48.9% (95% CI, 32.1%-65.9%; I2=87%), respectively. The local recurrence rate was 3.9% (95% CI, 2%-7.5%; I2=0%). The pooled rates of bleeding and perforation were 7.7% (95% CI, 4.5%-13%; I2=10%) and 5.3% (95% CI, 3.1%-8.9%; I2=0%), respectively. The rates of metachronous recurrence and additional surgery following ESD were 10% (95% CI, 5.2%-18.2%; I2=55%) and 13% (95% CI, 8.5%-19.3%; I2=54%), respectively. CONCLUSIONS: ESD is safe and effective for the resection of dysplastic lesions in IBD with an excellent pooled rate of en-bloc and R0 resection.

Green-Synthesized Silver and Selenium Nanoparticles Using Berberine: A Comparative Assessment of In Vitro Anticancer Potential on Human Hepatocellular Carcinoma Cell Line (HepG2).

A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers' (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.

Peroral endoscopic myotomy for spastic esophageal dysmotility among opioid users: a multicenter propensity score matching study.

BACKGROUND AND AIMS: Opioid-induced esophageal dysfunction (OIED) often presents as spastic esophageal disorders (SEDs) and esophagogastric junction outflow obstruction (EGJOO). The aim of this study was to evaluate and compare clinical outcomes of peroral endoscopic myotomy (POEM) for SEDs and EGJOO among opioid users and nonusers. METHODS: This propensity score (PS) matching study included consecutive opioid users and nonusers who underwent POEM for SEDs and EGJOO between January 2018 and September 2022. The following covariates were used for the PS calculation: age, sex, duration of symptoms, Eckardt score, type of motility disorder, and length of myotomy during POEM. Clinical response was defined as a post-POEM Eckardt score ≤3. RESULTS: A total of 277 consecutive patients underwent POEM during the study period. PS matching resulted in the selection of 64 pairs of patients strictly matched 1:1 (n = 128) with no statistically significant differences in demographic, baseline, or procedural characteristics or in the parameters considered for the PS between the 2 groups. Clinical response to POEM was significantly lower among opioid users (51 of 64 [79.7%]) versus nonusers (60 of 64 [93.8%]) (P = .03) at a median follow-up of 18 months. Among opioid users, higher opioid dose (>60 morphine milligram equivalents per day) was associated with a higher likelihood of failure to respond to POEM (odds ratio, 4.59; 95% confidence interval, 1.31-3.98; P = .02). CONCLUSIONS: Clinical response to POEM for SEDs and EGJOO is significantly lower among opioid users versus nonusers. There was a dose-relationship between opioids and response to POEM, with higher daily opioid usage associated with a higher likelihood of treatment failure.

Ambulatory Endoscopic Submucosal Dissection for Gastrointestinal Neoplasms: Trends and Associated Factors in the United States.

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for superficial gastrointestinal (GI) cancers.1,2 ESD practice is expanding significantly in the United States and Western countries. This is attributed to a shorter hospital stay, better quality of life, and fewer adverse events compared with surgery. In the United States, ESD usually is performed and managed in an outpatient setting (ambulatory ESD) or with an overnight hospital stay. This practice is in contrast to Eastern Asian countries, where 3 to 5 days of hospital stay is a routine process for observation after ESD. A Swedish study showed that patients with well-selected colorectal neoplasms (median tumor size, 37 mm) could be managed safely in an outpatient setting after ESD.3 A North American multicenter ESD study also reported that ambulatory ESD was safe and feasible in selected cases (noninvasive cancers, no adverse events, high-volume endoscopists with short procedure time).4 However, procedural and technical aspects that enable safe outpatient management of patients after ESD need to be investigated.

Development and initial validation of a video-based peroral endoscopic myotomy assessment tool.

BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.

Low delayed bleeding and high complete closure rate of mucosal defects with the novel through-the-scope dual-action tissue clip after endoscopic resection of large nonpedunculated colorectal lesions (with video).

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).

Settings of a novel electrosurgical generator to enable efficient and safe submucosal endoscopic procedures.

Background and study aims A novel electrosurgical generator unit (ESU), ConMed Beamer, was recently introduced to facilitate endoscopic submucosal dissection (ESD) by employing Automatic Cutting Effect (ACE) technology. Its use in submucosal endoscopy has yet to be investigated. The aim of this study was to evaluate the feasibility and safety of performing ESD and peroral endoscopic myotomy (POEM) using novel settings generated with ConMed Beamer ESU. Patients and methods This was a single-center prospective study of 59 consecutive patients undergoing ESD/POEM at a tertiary referral center. ESU settings were initially generated by testing in live animal models prior to first in-human study. The primary outcome was technical success. Secondary outcomes were procedure times, rate of en bloc/R0 resection, and rate of adverse events (AEs). Results A total of 44 patients (50 polyps) and 15 patients underwent ESD and POEM, respectively. En bloc resection, R0 resection, and curative resection rates were 90%, 77.1%, and 70.8%, respectively. Mean maximal length of the lesion was 3.07 cm ± 1.43 with an average dissection speed of 14.2 cm 2 /hr ± 11.1. Technical success was achieved in 100% of POEM patients. Mean time (minutes) to complete the POEM procedure was 50.1 min ± 12.4. Two major AEs occurred among all patients (3.4%). All intraprocedural bleeding events were controlled using the ConMed Beamer ESU. Conclusions ConMed Beamer ESU settings generated from this study were proven safe and effective in a prospective cohort of patients who underwent submucosal endoscopic procedures. This novel ESU can be added to the armamentarium of ESD capable generators.

Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome.

OBJECTIVES: Large surface area microparticle paclitaxel (LSAM-PTX) provides an intratumoral (IT) chemotherapeutic depot. Safety, tolerability, and tumor response to IT LSAM-PTX delivered by endoscopic ultrasound-fine needle injection were evaluated in subjects with unresectable locally advanced pancreatic cancer (LAPC). METHODS: Ten subjects treated in a dose escalation phase and 22 additional subjects receiving 2 injections, 4 weeks apart, of 15 mg/mL LSAM-PTX were followed for 12 months. Paclitaxel pharmacokinetics were evaluated, imaging at 3 and 6 months determined tumor response, and multiplex immunofluorescence was conducted to characterize local immune response. RESULTS: Most treatment-emergent adverse events were attributed to LAPC. Plasma paclitaxel levels were negligible. Eight subjects' tumors became resectable after IT LSAM-PTX, and 5 of 6 (83%) were resected with R0. Multiplex immunofluorescence of resected tumors demonstrated increased T cells, natural killer cells, and macrophages and decreased myeloid-derived suppressor cells. Six-month disease control rate was 94%, and median overall survival was 19.7 months in the 2-injection subjects. For nonresected and resected groups, overall survival times were 18.9 and 35.2 months, respectively. CONCLUSIONS: Neoadjuvant IT LSAM-PTX, in combination with SOC, was well tolerated and may provide benefits to LAPC patients, evidenced by enhanced immune response, improved disease control rate, restaging leading to surgery, and extended survival.