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Objectives: To evaluate the clinical outcomes of peroral cholangiopancreatoscopy (POCPS) using the 9-Fr eyeMAX for the diagnosis of pancreatobiliary diseases. Methods: This retrospective study enrolled 43 patients who underwent POCPS using the 9-Fr eyeMAX for diagnostic procedures at two tertiary referral centers between May 2023 and November 2024. The primary outcome was the incidence of adverse events following POCPS. Patient backgrounds, procedural details, technical success (successful insertion of the 9-Fr eyeMAX), and adequate tissue sampling were also analyzed. Results: Of the 43 patients, 32 were male, and 11 were female, with a median age of 75 years (range, 46-87 years). Peroral cholangioscopy (POCS) was performed on 30 patients. The final diagnosis in this cohort was an ampullary tumor (n = 2), extrahepatic bile duct cancer (n = 16), gallbladder cancer (n = 3), metastatic liver tumor (n = 1), and benign biliary stricture (n = 8). The adequate tissue sampling rate for the POCS was 86.4%. Adverse events after POCS occurred in two patients (6.7%), including mild pancreatitis (n = 1) and fever (n = 1). Peroral pancreatoscopy (POPS) was performed on 13 patients. The final diagnoses of all patients undergoing POPS were intraductal papillary mucinous neoplasms (IPMN), categorized as branch duct-type IPMN (n = 1), mixed-type IPMN (n = 8), and main duct-type IPMN (n = 4). The technical success rate was 92.3% (12/13). The tissue sampling rate for POPS was 83.6%. No adverse events, such as pancreatitis, were observed. Conclusions: The 9-Fr eyeMAX facilitates a safe POCPS procedure, achieving a high technical success rate and an adequate tissue sampling rate.
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Endoscopic antireflux therapy is a novel endoscopic treatment for refractory gastroesophageal reflux disease. We developed antireflux myoplasty (AR-MP), a modified version of antireflux mucoplasty (ARM-P), in which exposed bilateral sling fibers are sutured directly via endoscopic hand-suturing. AR-MP was performed on a 60-year-old man, resulting in symptomatic improvement and allowing discontinuation of acid-suppressive medication 3 months after the procedure. One month postoperatively, endoscopy showed an improvement in the Hill classification from grade 3 to grade 1. Before AR-MP, endoscopic pressure study integrated system findings showed a maximum intragastric pressure value of 13.7 mmHg, indicating a flat pattern. After AR-MP, maximum intragastric pressure exceeded 20 mmHg, and the pattern shifted to uphill. AR-MP is an innovative endoscopic technique that reconstructs the native antireflux mechanism by suturing the sling fibers and reforming the gastroesophageal flap valve. This innovative endoscopic procedure, like ARM-P, provides immediate symptom relief and represents a breakthrough in the endoscopic treatment of gastroesophageal reflux disease.
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Gastric abscess is a rare condition caused by gastric barrier damage. It is easily misdiagnosed in clinical practice as a cancer recurrence or submucosal tumor, especially after surgery or endoscopic submucosal dissection. With a relatively high mortality rate, the cause and clinical characteristics of gastric abscesses are obscure. To date, diagnostic evaluations have mostly included indirect gastroscopy and abdominal computed tomography. A definite diagnosis of gastric abscess is challenging, and unnecessary surgery is sometimes performed. Relatively few applications of endoscopic ultrasound (EUS) have been described. EUS-guided fine needle aspiration for diagnosis and drainage is not commonly used. Therefore, more experiences related to the cause and clinical characteristics of gastric abscesses should be reported. Further recognition of EUS ultrasonographic images and related minimally invasive EUS therapies are urgently needed. Herein, through a literature review of previous cases, we summarized the causes, clinical features, and diagnostic methods for gastric abscess. Moreover, we aimed to gain more experience diagnosing gastric abscesses by EUS for future differentiation and treatment strategies by endoscopy.
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Objectives: Post-sedation discharge criteria for outpatient endoscopy and time-out procedures immediately before endoscopic examinations are important for ensuring patient safety. This study used a web-based questionnaire to survey the implementation status and current situation of these practices in Japan in 2024. Methods: A self-administered questionnaire was conducted from December 2023 to January 2024 using Google Forms. Participants were primarily from facilities involved in endoscopy study groups and readers of an endoscopy-specific e-newsletter. Additionally, medical staff from endoscopic centers across Japan were invited to participate in collaboration with the Japan Gastroenterological Endoscopy Technicians Society. Results: A total of 1,495 valid responses (medical staff: 1197 [80%]; doctors: 298) were collected from 1168 facilities, after excluding duplicate responses. Among the participating facilities, 58% were general hospitals, 21% were clinics or health check-up centers, and 9% were university hospitals or national cancer centers. Post-sedation discharge criteria were implemented in 58% of facilities for esophagogastroduodenoscopy and 56% for colonoscopy, with the post-sedation recovery score used as the criterion in about half of these cases. Time-out procedures were implemented in 57% of the facilities for both esophagogastroduodenoscopy and colonoscopy. Items confirmed during time-out in more than half of the facilities included: patient's name, details of antithrombotic drugs, content of examination, drug allergies, underlying disease, date of birth, consent form, age, procedure start time, and patient's identification number. Conclusion: The implementation rate of post-sedation discharge criteria and time-out procedures was found to be close to 60%, reflecting the real-world situation in Japan in 2024.
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Wirsungocele, a cystic dilation at the end of the main pancreatic duct, is associated with recurrent acute pancreatitis. A 52-year-old man presented to our hospital with recurrent epigastric pain over an 8-month period with a history of multiple medical visits for the same complaint. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) revealed focal cystic dilatation at the end of the main pancreatic duct; thus, he was diagnosed with Wirsungocele. He underwent endoscopic pancreatic sphincterotomy and 5Fr 4 cm pancreatic duct stent placement; the pancreatic duct stent was removed 1 month later. Magnetic resonance imaging performed 3 months after discharge revealed no cystic dilation, and he has had no recurrence of pancreatitis for at least 6 months. Dysfunction of the sphincter of Oddi, weakening of the pancreatic duct wall, inflammation and recurrent stress, elevated intraductal pressure, and genetic and structural factors are suspected mechanisms behind the pathophysiology of Wirsungocele. Although the etiology of Wirsungocele is not known, its timely identification and treatment are critical to preventing recurrent episodes of pancreatitis. This case demonstrates the diagnostic value of combining MRCP and EUS as well as the therapeutic benefits of endoscopic intervention, including sphincterotomy and stent placement, in managing Wirsungocele-associated recurrent pancreatitis. Given the paucity of reports on recurrent pancreatitis due to the Wirsungocele, we herein report this case and review the literature.
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Objectives: Over-the-scope clips (OTSCs) are considered an effective endoscopic tool for managing upper gastrointestinal bleeding, including duodenal ulcers, mostly based on data from high-volume centers with expert endoscopists. This study aimed to evaluate the clinical safety of OTSCs in regional hospital backgrounds and identify the factors associated with unsuccessful hemostasis. Methods: We conducted a retrospective study of 30 patients with duodenal ulcer bleeding who underwent OTSC placement at a regional core hospital in Japan between April 2014 and January 2025. Clinical outcomes, rebleeding rates, complications, and subgroup analyses by ulcer location, Forrest classification, and operator experience were evaluated. Results: Primary hemostasis was achieved in 28 of 30 patients (93.3%). Rebleeding occurred in two cases (6.7%) but was successfully managed endoscopically. Both hemostasis failures involved Forrest Ia ulcers on the posterior duodenal wall. Subgroup analysis revealed significantly lower success rates for Forrest Ia (66.7%) and posterior wall lesions (33.3%). No significant differences in outcomes were observed between experienced and less-experienced endoscopists. Postprocedural complications included mild pancreatitis and duodenal stricture, both managed conservatively. OTSC was used as a first-line modality in 10 cases and as salvage therapy in 20, with all failures occurring in the latter. Conclusion: OTSC is a safe and effective hemostatic modality for duodenal ulcer bleeding, even in regional hospitals with limited resources and staffing. It is particularly useful when rapid intervention is required and alternative treatments are not readily available. However, anatomical challenges such as posterior wall location and Forrest Ia classification may predict technical failure.
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We report an uncommon case of perforated peritonitis resulting from the migration of a single-puncture gastric wall fixation device following percutaneous endoscopic gastrostomy. An 83-year-old male developed acute peritonitis 6 days post-procedure, requiring emergency surgery. One fixation device was found embedded in the abdominal wall, and gastric perforation was identified. To our knowledge, this is the first reported case of peritonitis caused by T-fastener migration outside the gastric wall.
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Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation-inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drug-resistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.
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GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein-protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.
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Ischemic stroke is a significant global health crisis, frequently resulting in disability or death, with limited therapeutic interventions available. Although various intrinsic reparative processes are initiated within the ischemic brain, these mechanisms are often insufficient to restore neuronal functionality. This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option. This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events, with focus on the impact of stem cell-based therapies on neural stem cells. Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-to-cell contact and through the secretion of growth factors and exosomes. Additionally, implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called "biobridges." Furthermore, xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects, thereby supporting endogenous neuroregeneration. Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment, we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types. These approaches include: (1) co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis; (2) synergistic administration of stem cells and their exosomes to amplify paracrine effects; and (3) integration of stem cells within hydrogels, which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits. This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
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Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals. Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis, prognostic assessments, and the development of targeted therapies. This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease, focusing on the detection of specific proteins, metabolites, and other biomarkers in blood, cerebrospinal fluid, and saliva. These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease, which includes protein misfolding, neurodegeneration, inflammation, and oxidative stress. The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease. This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease. Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease, further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.
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Alzheimer's disease, a progressively degenerative neurological disorder, is the most common cause of dementia in the elderly. While its precise etiology remains unclear, researchers have identified diverse pathological characteristics and molecular pathways associated with its progression. Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease. These non-coding RNAs regulate several biological processes critical to the advancement of the disease, offering promising potential as therapeutic targets and diagnostic biomarkers. Therefore, this review aims to investigate the underlying mechanisms of Alzheimer's disease onset, with a particular focus on microRNAs, long non-coding RNAs, and circular RNAs associated with the disease. The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs. It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease, as well as how these non-coding RNAs influence the disease's progression by regulating gene expression and protein functions. For example, miR-9 targets the UBE4B gene, promoting autophagy-mediated degradation of Tau protein, thereby reducing Tau accumulation and delaying Alzheimer's disease progression. Conversely, the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA, promoting the generation of amyloid-ß and accelerating Alzheimer's disease development. Additionally, circular RNAs play significant roles in regulating neuroinflammatory responses. By integrating insights from these regulatory mechanisms, there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease. This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs, potentially paving the way for early detection and novel treatment strategies.
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Introduction: Bile leakage is one of the complications after hepatobiliary surgery, causing intra-abdominal infections, and is sometimes difficult to treat. The purpose of our study was to investigate the factors related to severity and to evaluate the efficacy of endoscopic treatment. Methods: This was a retrospective multicenter cohort study conducted at three tertiary care medical centers. The severity of bile leakage was classified per the International Study Group of Liver Surgery, and Grades B and C (requiring some intervention or reoperation) were considered as severe. Results: The subjects were 59 patients. The surgical procedures were 31 cholecystectomies, 23 hepatectomies, and five pancreaticoduodenectomies. The severity was Grade A/B/C: 17/40/2. Multivariate logistic regression analysis found that age (unit odds ratio [UOR], 1.09; 95% confidence interval [CI], 1.0-1.19; p = 0.049) and days from surgery to bile leak (UOR, 1.18; 95% CI, 1.04-1.35; p = 0.012) were independent predictors of bile leak severity. Of 40 Grade B biliary leakage patients, 37 patients underwent endoscopic drainage, of which 11 also received intra-abdominal abscess drainage. Eventually, bile leakage was successfully treated in all patients after several endoscopic drainage sessions, and the median drainage period was 18 days (inter-quartile range: 13-35). Conclusion: In the management of bile leakage after hepatobiliary surgery, elderly patients or patients with late onset of bile leak may be at high risk of severity. Endoscopic biliary drainage is considered a safe and effective treatment for severe patients.
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Self-expandable metallic and plastic stents have been used for biliary tract injuries, but they are not entirely adequate as treatments. This study investigated the potential of our novel self-expandable bioabsorbable covered stent (SEBCS) to treat bile duct injuries. We developed a novel SEBCS by covering a self-expandable bioabsorbable stent with a bioabsorbable tube. Five pigs underwent laparotomy after being placed under general anesthesia. A 5-mm incision was made in the extrahepatic bile duct, followed by the insertion of an SEBCS. Postoperatively, hepatobiliary enzyme levels were measured. At 10 weeks postoperatively, a histological evaluation of the injured area and cholangiogram were performed. The SEBCS was successfully inserted into the extrahepatic bile ducts of all animals. The histological evaluation at 10 weeks postoperatively showed epithelial regeneration with numerous peribiliary glands, including at the injury site. Cholangiography revealed no stenosis in the injured area. Hematological and biochemical analyses revealed mild elevation of biliary enzyme levels on day 10 postoperatively compared with preoperative levels; these levels returned to preoperative values by week 10. This novel SEBCS technique demonstrated the potential to regenerate bile ducts at the site of extrahepatic bile duct injury and may be a promising endoscopic treatment for biliary tract injuries.
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Introduction: Non-anesthesiologist-administered propofol (NAAP) sedation for outpatient endoscopy has proven to be safe. However, implementing NAAP in Western countries faces challenges, and propofol-based sedation is still largely administered by anesthetists. For low-risk patients, anesthesiologist-administered propofol (AAP) could represent an avoidable waste of healthcare resources. Methods: This research consisted of two phases. The first is a retrospective study comparing NAAP and AAP for outpatient endoscopy at a tertiary center, with the primary outcome being the rate of adverse events (AEs). Propensity score matching was performed to balance baseline characteristics between the two groups. The second phase involved a budget impact model to assess the economic impact of using NAAP instead of AAP for low-risk patients, both locally and nationally, between 2023 and 2025. Results: Between May 2019 and November 2021, 2721 patients undergoing esophagogastroduodenoscopies (EGDs; NAAP 2439 and AAP 282) and 2748 colonoscopies (NAAP 2491 and AAP 257) were enrolled. Overall, the AE rates were similar between the cohorts (esophagogastroduodenoscopies: NAAP 1.1% vs. AAP 0.8%, p = 0.81; colonoscopies: NAAP 1.8% vs. AAP 3.5%, p = 0.20). All NAAP-related AEs were minor.The budget impact model revealed that adopting NAAP instead of AAP would save 124,724,659 and 2223 working days for healthcare professionals for the Italian National Health System (NHS) between 2023 and 2025. Conclusion: NAAP has a comparable AE rate to AAP for low-risk outpatient endoscopy. Implementing NAAP instead of AAP could save over 100 million and 2000 working days for the Italian NHS between 2023 and 2025. Wider adoption could improve healthcare resource allocation.
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Objectives: Gastrointestinal stromal tumors (GISTs) are vascular tumors that can cause significant gastrointestinal hemorrhage. While endoscopic treatment is common for other hemorrhagic disorders, its role in GIST-related hemorrhage remains unclear. This study presents a case series of five patients who underwent successful endoscopic hemostasis for upper gastrointestinal GISTs and explores potential risk factors for hemorrhage. Methods: This single-center retrospective study included patients diagnosed with upper gastrointestinal GISTs between January 2013 and December 2022. Of the 61 eligible patients, the clinical courses of five patients who underwent endoscopic hemostasis were reviewed. In addition, an exploratory analysis was conducted to identify risk factors associated with GIST-related hemorrhage by comparing hemorrhagic and non-hemorrhagic groups using univariate analyses. Results: Five patients underwent successful endoscopic hemostasis using hypertonic saline-epinephrine injection and/or clipping for hemorrhage from exposed vessels at the ulcer. Consequently, emergency surgery within 24 h was avoided in all cases, and elective surgery was conducted between 7 and 51 days. Additionally, ulcer formation (odds ratio [OR] 37.20; 95% confidence interval [CI] 2.40-582.00; p < 0.01), elevated white blood cell count (OR 1.05; 95% CI 1.01-1.09; p = 0.03), and elevated body mass index (OR 1.22, 95% CI 1.02-1.47, p = 0.03) were identified as risk factors for hemorrhage in the exploratory analysis. Conclusions: Endoscopic hemostasis may help avoid emergency surgery in GIST-related hemorrhage when hemorrhage points are clearly visualized. Ulceration may serve as a predictive factor for hemorrhage; therefore, early surgical intervention should be considered in GISTs with ulceration.
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Background: Duodenal invasion is a risk factor for early recurrent biliary obstruction (RBO) due to the increased risk of duodenobiliary reflux. Transpapillary biliary drainage using anti-reflux metal stents (ARMS) and endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) are two different strategies for this condition. Methods: We retrospectively reviewed unresectable pancreatic cancer (PC) patients with duodenal invasion who underwent either transpapillary biliary drainage using duckbill-type ARMS (D-ARMS) or EUS-HGS for malignant distal biliary obstruction (MDBO). Technical and clinical success, causes of RBO, non-RBO adverse events (AEs), time to RBO (TRBO), and endoscopic reintervention (ERI) were compared between groups. Results: Forty-four patients were included (D-ARMS: 22, EUS-HGS: 22). Technical and clinical success rates, and non-RBO AE rates (9.1% vs. 36.4%, p = 0.069) were not significantly different between groups. Common causes of RBO were biliary debris/stones in the D-ARMS group and hyperplasia in the EUS-HGS group. Overall RBO rates (33.3% vs. 45.0%, p = 0.53), median TRBO (246 vs. 222 days, p = 0.98), and outcomes after ERI were comparable between groups. Conclusions: Transpapillary biliary drainage using D-ARMS may be a viable option in managing MDBO with duodenal invasion, especially for non-high-volume centers, when both procedures are technically feasible.
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Pancreatic neuroendocrine neoplasms are rare but occasionally encountered. They are generally highly vascularized solid tumors, often round in shape with clear boundaries, defined contours, and a homogeneous internal structure. However, they can also present with atypical features, such as cystic degeneration, hemorrhage, calcification, and fibrosis, making diagnosis difficult in some cases. They are also known as comorbidities of multiple endocrine neoplasia type 1 (MEN1). This report describes a case in which endoscopic ultrasound (EUS) led to a diagnosis of MEN1. A 50-year-old man was referred to our hospital for examination of a mass in the pancreatic body. An EUS-guided fine-needle biopsy was performed, and a histological diagnosis of neuroendocrine tumor (NET) was made. In addition, the NET was also identified in the duodenum. Serum calcium and parathyroid hormone levels were elevated. Examination of the parathyroid and pituitary glands revealed concurrent hyperparathyroidism and a pituitary adenoma, confirming the diagnosis of MEN1, including a NET in the duodenum.
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JOURNAL/nrgr/04.03/01300535-202601000-00037/figure1/v/2025-06-09T151831Z/r/image-tiff Neuroserpin, a secreted protein that belongs to the serpin superfamily of serine protease inhibitors, is highly expressed in the central nervous system and plays multiple roles in brain development and pathology. As a natural inhibitor of recombinant tissue plasminogen activator, neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia. However, the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear. In this study, we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models, respectively. The models were used to investigate the neuroprotective effects of neuroserpin. Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia, initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis, which was followed by a later apoptotic response. Notably, ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons. Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules, the reduction in protein synthesis, and the upregulation of apoptotic transcription factors. This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion, as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion. However, the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin. Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.