UNASSIGNED: Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI.
UNASSIGNED: A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining.
UNASSIGNED: GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well.
UNASSIGNED: The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.

UNASSIGNED: The impact of stroma-targeting therapy on tumor immune suppression is largely unexplored. An RNA oligonucleotide, STNM01, has been shown to repress carbohydrate sulfotransferase 15 (CHST15) responsible for tumor proteoglycan synthesis and matrix remodeling. This phase I/IIa study aimed to evaluate the safety and efficacy of STNM01 in patients with unresectable pancreatic ductal adenocarcinoma (PDAC).
UNASSIGNED: This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC. A cycle comprised three 2-weekly endoscopic ultrasound-guided locoregional injections of STNM01 at doses of 250, 1,000, 2,500, or 10,000 nM in combination with S-1 (80-120 mg twice a day for 14 days every 3 weeks). The primary outcome was the incidence of dose-liming toxicity (DLT). The secondary outcomes included overall survival (OS), tumor response, changes in tumor microenvironment on immunohistopathology, and safety (jRCT2031190055).
UNASSIGNED: A total of 22 patients were enrolled, and 3 cycles were repeated at maximum; no DLT was observed. The median OS was 7.8 months. The disease control rate was 77.3%; 1 patient showed complete disappearance of visible lesions in the pancreas and tumor-draining lymph nodes. Higher tumoral CHST15 expression was associated with poor CD3+ and CD8+ T cell infiltration at baseline. STNM01 led to a significant reduction in CHST15, and increased tumor-infiltrating CD3+ and CD8+ T cells in combination with S-1 at the end of cycle 1. Higher fold increase in CD3+ T cells correlated with longer OS. There were 8 grade 3 adverse events.
UNASSIGNED: Locoregional injection of STNM01 was well tolerated in patients with unresectable PDAC as combined second-line therapy. It prolonged survival by enhancing T cell infiltration in tumor microenvironment.
UNASSIGNED: The present study was supported by the Japan Agency for Medical Research and Development (AMED).

The digestive system is one of the most common sites of malignancies in humans. Since gastrointestinal tumors represent a massive global health burden both in terms of morbidity and health care expenditures, scientists continuously develop novel diagnostic and therapeutic methods to ameliorate the detrimental effects of this group of diseases. Apart from the well-established role of the endoscopic ultrasound (EUS) in the diagnostic course of gastrointestinal and hepatobiliary malignancies, we have recently become acquainted with a vast array of its therapeutic possibilities. A multitude of previously established, evidence-based methods that might now be guided by the EUS emerged: Radiofrequency ablation, brachytherapy, fine needle injection, celiac plexus neurolysis, and endoscopic submucosal dissection. In this review we endeavored to provide a comprehensive overview of the role of these methods in different malignancies of the digestive system, primarily in the treatment and symptom control in pancreatic cancer, and additionally in the management of hepatic, gastrointestinal tumors, and pancreatic cysts.

Endoscopic ultrasound-guided fine needle injection (EUS-FNI) has been proposed as a novel technique for local delivery of antitumor agents to refractory tumors, including pancreatic cancer. However, the present outcome of this strategy remains insufficient, and further improvements as well as novel agents and injection devices are required. The aim of the study was to determine the feasibility of a newly designed \'multiple injectable needle\' (MIN) for EUS-FNI and the resulting improvements in the drug distribution to the tumor in comparison with straight-type needles. Human pancreatic cancer BxPC-3 cells or orthotopic tumor were transplanted subcutaneously into athymic rats. Ethanol was injected into subcutaneous tumors using a MIN or straight-type needle. Sequential sections of subcutaneous tumors were stained with hematoxylin and eosin, and tumors and injury areas were quantified using ImageJ software. In the orthotopic tumors, injection of the outer needle of the MIN, advancement of the inner needle and ethanol infusion were monitored by EUS. Injury volume of subcutaneous tumors using a MIN was greater than that with the straight-type needles, except for large tumors. Injecting process using MIN was monitored with endoscopic ultrasound (EUS). This study showed improvement in the drug distribution in a tumor, following injection with MIN compared to straight-type needles, suggesting the novel device to be feasible for use in EUS-FNI.