EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: Multi-site feasibility study.

The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas.

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses.

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses.

A Multi-Institutional Safety and Feasibility Study Exploring the Use of Hydrogel to Create Spatial Separation between the Pancreas and Duodenum in Patients with Pancreatic Cancer.

Purpose: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum.

Methods And Materials: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove.

Balancing Safety and Efficacy to Determine the Most Suitable Size of Imaging-Visible Embolic Microspheres for Bariatric Arterial Embolization in a Preclinical Model.

Objectives: To identify the most suitable size of imaging-visible embolic agents with balanced safety and efficacy for bariatric arterial embolization (BAE) in a preclinical model.

Materials And Methods: Twenty-seven pigs were divided into 3 cohorts. In Cohort I, 16 pigs were randomized to receive (n = 4 each) 40-100-μm microspheres in 1 or 2 fundal arteries, 70-340-μm radiopaque microspheres in 2 fundal arteries, or saline.

Detecting Somatic Mutations for Well-Differentiated Pancreatic Neuroendocrine Tumors in Endoscopic Ultrasound-Guided Fine Needle Aspiration with Next-Generation Sequencing.

Background: Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogenous behavior, whereby some small tumors are aggressive with a propensity for metastasis. Detection of somatic mutations associated with aggressive biology may help with patient stratification and surgical decision-making in patients with well-differentiated PanNETs. Using next-generation sequencing (NGS), we investigated the feasibility of detecting somatic mutations in endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) specimens and determining the mutational concordance between the EUS-FNA specimens and the primary tumors.

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.

Background: Neoadjuvant therapy (NAT) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC); however, accurate prediction of therapeutic response to NAT remains a pressing clinical challenge. Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) was previously identified as a prognostic biomarker in PDAC. This study aims to explore whether SIA-IgG expression in treatment-naïve fine needle aspirate (FNA) biopsy specimens could predict the pathological response (PR) to NAT for PDAC.

Up-Scale Synthesis of -(CH=CH)CHCHCHCHCl and -ClCHSiR by CuCN-Catalyzed Coupling Reactions of Grignard Reagents with Organic Halides.

Grignard reagents featuring carbanion characteristics are mostly unreactive toward alkyl halides and require a catalyst for the coupling reaction. With the need to prepare -(CH=CH)CHCHCHCHCl on a large scale, the coupling reaction of -(CH=CH)CHMgCl with BrCHCHCHCl was attempted to screen the catalysts, and CuCN was determined to be the best catalyst affording the desired compound in 80% yield with no formation of Wurtz coupling side product CH=CHCH-CHCH=CH. The -(CH=CH)CHCu(CN)MgCl species was proposed as an intermediate based on the X-ray structure of PhCu(CN)Mg(THF)Cl.

Generation and multiomic profiling of a double-knockout gastroesophageal junction organoid model.

Inactivation of the tumor suppressor genes tumor protein p53 () and cyclin-dependent kinase inhibitor 2A () occurs early during gastroesophageal junction (GEJ) tumorigenesis. However, because of a paucity of GEJ-specific disease models, cancer-promoting consequences of and inactivation at the GEJ have not been characterized. Here, we report the development of a wild-type primary human GEJ organoid model and a CRISPR-edited transformed GEJ organoid model.

RAD51B Harbors Germline Mutations Associated With Pancreatic Ductal Adenocarcinoma.

Purpose: Genetic alterations in many components of the homologous recombination, DNA damage response, and repair (HR-DDR) pathway are involved in the hereditary cancer syndromes, including familial pancreatic cancer. HR-DDR genes beyond , , , and may also mutate and confer the HR-DDR deficiency in pancreatic ductal adenocarcinoma (PDAC).

Methods: We conducted a study to examine the genetic alterations using a companion diagnostic 15-gene HR-DDR panel in PDACs.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

Purpose: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies.

Methods: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I higher-stage).

Endoscopic ultrasound guided interventions in the management of pancreatic cancer.

There has been a growing interest in developing endoscopic ultrasound (EUS)-guided interventions for pancreatic cancer, some of which have become standard of care. There are two main factors that drive these advancements to facilitate treatment of patients with pancreatic cancer, ranging from direct locoregional therapy to palliation of symptoms related to inoperable pancreatic cancer. Firstly, an upper EUS has the capability to access the entire pancreas-lesions in the pancreatic head and uncinate process can be accessed from the duodenum, and lesions in the pancreatic body and tail can be accessed from the stomach.

Association of Matrix Metalloproteinase 7 Expression With Pathologic Response After Neoadjuvant Treatment in Patients With Resected Pancreatic Ductal Adenocarcinoma.

Importance: The use of neoadjuvant therapy (NAT) in resectable pancreatic ductal adenocarcinoma (PDAC) remains controversial. A favorable pathologic response (complete or marked tumor regression) to NAT is associated with better outcomes in patients with resected PDAC. The role of NAT for early systemic control compared with immediate surgical resection for PDAC is under investigation.

Finite Element-Based Personalized Simulation of Duodenal Hydrogel Spacer: Spacer Location Dependent Duodenal Sparing and a Decision Support System for Spacer-Enabled Pancreatic Cancer Radiation Therapy.

Purpose: Pancreatic cancer is the fourth leading cause of cancer-related death, with a very low 5-year overall survival rate (OS). Radiation therapy (RT) together with dose escalation significantly increases the OS at 2 and 3 years. However, dose escalation is very limited due to the proximity of the duodenum.

SUPT4H1-edited stem cell therapy rescues neuronal dysfunction in a mouse model for Huntington's disease.

Huntington's disease (HD) is a severe inherited neurological disorder caused by a CAG repeat expansion in the huntingtin gene (HTT), leading to the accumulation of mutant huntingtin with polyglutamine repeats. Despite its severity, there is no cure for this debilitating disease. HTT lowering strategies, including antisense oligonucleotides (ASO) showed promising results very recently.

The Feasibility of Haar Feature-Based Endoscopic Ultrasound Probe Tracking for Implanting Hydrogel Spacer in Radiation Therapy for Pancreatic Cancer.

Purpose: We proposed a Haar feature-based method for tracking endoscopic ultrasound (EUS) probe in diagnostic computed tomography (CT) and Magnetic Resonance Imaging (MRI) scans for guiding hydrogel injection without external tracking hardware. This study aimed to assess the feasibility of implementing our method with phantom and patient images.

Materials And Methods: Our methods included the pre-simulation section and Haar features extraction steps.

Important Quality Metrics and Standardization in Endoscopy.

Quality metrics and standardization has become critical as the Affordable Care Act mandates that the Center for Medicare and Medicaid Services change reimbursement from volume to a value-based system. While the most commonly used quality indicators are related to that of colonoscopy, quality metrics for other procedures and endoscopy units have been developed mainly by the American College of Gastroenterology and the American Society of Gastrointestinal Endoscopy. Data to show that these quality metrics, especially in the field of advanced endoscopy as well as in the era of COVID-19 pandemic, can improve patient outcomes, are anticipated.

Endoscopic Ultrasound-Guided Fiducial Placement for Stereotactic Body Radiation Therapy in Pancreatic Malignancy.

Stereotactic body radiation therapy (SBRT) is an important treatment option for pancreatic cancer, which is known to be one of the malignancies with the worst prognosis. However, the high radiation doses delivered during SBRT may cause damage to adjacent radiosensitive organs. To minimize such damage, fiducial markers are used for localization during SBRT for pancreatic cancer.

EUS-guided hydrogel microparticle injection in a cadaveric model.

Background And Aims: A potential method to reduce gastrointestinal toxicity during radiation therapy in pancreatic head cancer is to create a physical space between the head of the pancreas (HOP) and the duodenum. To date, there have been early reports on the feasibility of endoscopic ultrasound (EUS)-guided hydrogel injection into the interface between the HOP and the duodenum to increase the peri-pancreatic space for radiotherapy. We aimed to evaluate the technical feasibility of EUS-guided hydrogel injection for the creation of space at the peri-pancreatic interface in a cadaveric model.

Novel Long Noncoding RNA miR205HG Functions as an Esophageal Tumor-Suppressive Hedgehog Inhibitor.

Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators of biological pathways. However, involvement of lncRNAs in the development of BE and EAC has not been well-studied.