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Background/Aims: Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the long-term outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. Methods: This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean follow-up duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. Results: Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). Conclusion : s: Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Background/Aims: There are limitations in treating ampullary adenomas with intraductal extension using conventional endoscopic modalities. Endoscopic intraductal radiofrequency ablation (ID-RFA) may be useful for treating intraductal (common bile duct [CBD] and/or pancreatic duct [PD]) extensions of ampullary adenomas, but long-term data are lacking. We thus evaluated the long-term outcomes of endoscopic ID-RFA for managing ampullary adenomas with intraductal extension. Methods: Prospectively collected endoscopic ID-RFA database at Asan Medical Center was reviewed to identify consecutive patients with ampullary adenoma who underwent ID-RFA for intraductal extension between January 2018 and August 2021. Technical success, short-term and long-term clinical success, and adverse events were evaluated. Results: A total of 29 patients (14 CBD, 1 PD, and 14 CBD and PD) were analyzed. All patients had undergone endoscopic snare papillectomy prior to ID-RFA. A median of one session of ID-RFA (range, 1 to 3) for residual or relapsed intraductal extension of ampullary adenoma were successfully performed (technical success=100%). Both biliary and pancreatic stenting were routinely performed after ID-RFA to prevent ductal stricture. After a median follow-up of 776 days (interquartile range, 470 to 984 days), the short-term and long-term clinical success rates were 93% and 76%, respectively. Seven patients experienced procedural adverse events and three patients developed ductal strictures. Conclusions: Endoscopic ID-RFA showed good long-term outcomes in treating residual or relapsed ampullary adenomas with intraductal extension. Repeated ID-RFA may be considered as an option for managing recurrence. Further studies are needed to standardize the procedure.

The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962–0.9993), accuracy (93.5–111.73%), and precision (1.7–14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 μL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 μg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 μg/cm2), respectively.

This study aimed to evaluate the ejection pressure and the correlation of the findings with the occurrence of internal cracks within bilayer tablets (BLTs) consisting of metformin HCl (MF) and evogliptin tartrate (EG). Then, the mechanism of tablet failure was provided by the finite element method (FEM). The ejection pressure and the difference in diameter depending on MAIN-P were evaluated to understand the correlation between ejection pressure and change in the BLT internal structure. The ejection pressure and the difference in diameter increased as the MAIN-P increased, then steeply decreased from 350 MPa to 375 MPa of MAIN-P, despite there being no pattern in compaction breaking force and porosity. The mechanical integrity at the BLT interface was weakened by internal cracks, reducing ejection pressure. The stress distribution analysis during the compression revealed that crack formation caused by entrapped air located at the center of the BLT interface may not propagate due to concentrated stress, which promotes a tight bond at the edge of the BLT. Furthermore, complete delamination can occur in the ejection process due to localized and intensive shear stresses at the BLT interface. These findings indicate that the mechanisms of internal cracking and delamination were successfully confirmed by FEM simulation. Moreover, measuring ejection pressure before BLT manufacturing can prevent invisible tablet cracks without damaging the tablets.

Background/Aims: Endoscopic ultrasonography (EUS) provides high-resolution images and is superior to computed tomography (CT) scan in diagnosing small pancreatic ductal adenocarcinoma (PDAC). As a result, the use of EUS for early detection of PDAC has attracted attention. This study aimed to identify the clinical and radiological characteristics of patients with PDAC diagnosed by EUS but not found on CT scan. Methods: The medical records of patients diagnosed with PDAC at 12 tertiary referral centers in Korea from January 2003 to April 2019 were reviewed. This study included patients with pancreatic masses not clearly observed on CT scan but identified on EUS. The clinical characteristics and radiological features of the patients were analyzed, and survival analysis was performed. Results: A total of 83 patients were enrolled. The most common abnormal CT findings other than a definite mass was pancreatic duct dilatation, which was identified in 61 patients (73.5%). All but four patients underwent surgery. The final pathologic stages were as follows: IA (n=31, 39.2%), IB (n=8, 10.1%), IIA (n=20, 25.3%), IIB (n=17, 21.5%), III (n=2, 2.5%), and IV (n=1, 1.4%). The 5-year survival rate of these patients was 50.6% (95% confidence interval, 38.8% to 66.7%). Elevated liver function testing and R1 resection emerged as significant predictors of mortality in the multivariable Cox regression analysis. Conclusions: This multicenter study demonstrated favorable long-term prognosis in patients with PDAC diagnosed by EUS but indeterminate on CT scan. EUS should be considered for patients with suspected PDAC but indeterminate on CT scan.

The objectives of this study were to evaluate the delamination of convex-shaped metformin HCl (MF) and evogliptin tartrate (EG) multi-layer tablets depending on the pre-compression and main compression pressures and simultaneously correlate these results with those of a surface roughness analysis. Free-flowing MF and EG (median diameters of 38.3 and 44.7 μm, respectively) granules prepared using the wet granulation method were pre-compressed and subsequently compressed into bilayer and trilayer tablets using a universal testing machine. The compaction force required to break the tablets increased linearly as the main compression pressure increased (30–150 MPa). Conversely, the interfacial strength and compaction breaking force decreased as the pre-compression pressure increased (10–110 MPa). A surface roughness analysis employing a profilometer revealed that the first layer (MF) roughness drastically decreased from 5.89 to 0.51 μm (Ra, arithmetic average of profile height deviations from the mean line) as the pre-compression pressure increased from 10 to 150 MPa in the bilayer tablet. Accordingly, the decrease in the roughness of the first layer reduced the inter-penetration at the interface, as observed via energy dispersive spectrometer (EDS)-equipped scanning electron microscopy, decreasing the interfacial bonding strength and causing delamination of the MF/EG multi-layer tablets. These findings indicate the significance of roughness control in the actual preparation of multi-layer tablets and the usefulness of profilometer- and EDS-based surface analyses for interpreting the delamination of multi-layer tablets.

GV1001, a human telomerase reverse transcriptase catalytic subunit-derived 16-mer peptide, has been developed as a novel anticancer vaccine against various cancers including pancreatic cancer. In the current study, we demonstrate the regulatory roles and mechanisms of GV1001 in endothelial cell responses in vitro and microvessel sprouting ex vivo. GV1001 markedly inhibits vascular endothelial growth factor-A (VEGF-A)-stimulated endothelial cell permeability, proliferation, migration, invasion, tube formation as well as microvessel outgrowth from rat aortic rings. These anti-angiogenic effects of GV1001 were associated with the inhibition of VEGF-A/VEGFR-2 signaling pathways, redistribution of vascular endothelial-cadherin to cell–cell contacts, and down-regulation of VEGFR-2 and matrix metalloproteinase-2. Furthermore, GV1001 suppresses the proliferation and invasion of non-small cell lung cancer cells, and the release of VEGF from the cells, suggesting the regulatory role of GV1001 in tumor-derived angiogenesis as well as cancer cell growth and progression. Collectively, our study reports the pharmacological potential of GV1001 in the regulation of angiogenesis, and warrants further evaluation and development of GV1001 as a promising therapeutic agent for a variety of angiogenesis-related diseases including cancer.

Spiraea prunifolia has been used in Korean traditional medicine to treat malaria, fever, and emetic conditions. Previous investigation reported that several parts of Spiraea prunifolia show various functional effects. However, the effect of Spiraea prunifolia leaves extract (SPE) on anti-obesity remains unclear. Therefore, we used a high-fat diet (HFD)-induced obese mouse model in this study to investigate the effects of SPE on adipogenesis, lipogenesis, and β-oxidation. Oral administration of SPE in HFD-induced obese mice considerably reduced body weight, serum levels such as total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, adipose tissue weight, and adipocyte cell size. Moreover, SPE significantly decreased protein expression levels of adipogenesis and lipogenesis related genes such as CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte protein 2, acetyl-CoA carboxylase, and fatty acid synthase in epididymal adipose tissues. SPE treatment induced the protein expression of carnitine palmitoyl transferase-1, which might have promoted phosphorylated AMP-activated protein kinase-medicated β-oxidation. The present study reveals an anti-adipogenic, anti-lipogenic, β-oxidation effects of SPE in vivo and represents AMP-activated protein kinase signaling as targets for SPE.

Background/Aims: Interventional endoscopists may utilize contrast-enhanced harmonic endoscopic ultrasound (CEHEUS) for image guidance during radiofrequency ablation (RFA) because of its capability to delineate real-time tumor perfusion dynamics. The purpose of this study was to assess the utility of CEH-EUS for the guidance and monitoring of endoscopic RFA. Methods: Nineteen consecutive patients with solid abdominal tumors who underwent CEH-EUS and endoscopic RFA were included. The extent of the ablation was assessed by CEH-EUS at 5 to 7 days after RFA. Additional RFAs were performed under CEH-EUS guidance. Results: The diagnoses were as follows: nonfunctioning neuroendocrine tumor (n=13), solid pseudopapillary neoplasm (SPN) (n=2), insulinoma (n=1), left adrenal adenoma (n=2), and left adrenal oligometastasis (n=1). Pre-CEH-EUS findings revealed that 17 cases showed hyperenhanced patterns and two cases of SPN showed isoenhanced patterns. CEH-EUS-assisted RFA was technically feasible in all 19 patients. After the first RFA session, seven patients of the treated tumors showed the disappearance of intratumoral enhancement on CEH-EUS, whereas 12 showed residual contrast enhancement. Twelve patients with incomplete ablation were further treated with additional RFA under real-time CEH-EUS guidance. Radiologic complete response was observed in 13 patients (68.4%). Among the 35 ablation procedures, the only adverse events were two episodes of pancreatitis (5.7%; 1 moderate and 1 mild). During the median follow-up of 28 months, the local recurrence rate was 7.7%. Conclusions: The application of CEH-EUS for RFA could be helpful in assessing early treatment response after ablation and targeting residual viable tumors during additional ablation sessions.

Endoscopic ultrasound (EUS)-guided fine-needle aspiration was introduced in the early 1990s. EUS has evolved from a diagnostic modality to a therapeutic tool for patients with various pancreatic neoplasms. Recent advances in EUS-guided interventions include drainage and ablation. EUS-guided treatment provides a minimally invasive option for patients with pancreatic neoplasms instead of surgery or the percutaneous approach. This review aimed to provide an overview of the current EUS-guided ablation treatments, such as ethanol ablation and radiofrequency ablation, for treating various pancreatic tumors.

Background: As a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation. Methods: C2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins. Results: Rb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation. Conclusion: Rb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy. Keywords: Akt/mTOR signaling, Hypertrophy, Myoblast differentiation, Rb1, Rb2

Background/Aims: The natural history of spontaneous decrease in the size of pancreatic cystic lesions (PCLs) without high-risk stigmata is under investigation. This study aimed to investigate the timing of spontaneous decrease in the size of PCLs without high-risk stigmata and to identify the characteristics associated with their complete resolution. Methods: From 2000 to 2016, patients with spontaneous decreases in PCL size on computed tomography (CT) and/or magnetic resonance imaging (MRI) who had at least 1 year of follow-up were evaluated retrospectively. Results: A total of 78 patients underwent follow-up for an average of 55.7 months. Most patients were asymptomatic, and 35 (37.2%) showed complete resolution. The initial mean PCL size was 1.6±0.9 cm (range, 0.5 to 5.6 cm). The average time to initial decrease in size and complete resolution of PCLs were 32.1 and 41.5 months, respectively. Compared with PCLs that completely resolved, presence of underlying malignancy was associated with partial resolution of PCLs in multivariable analysis (hazard ratio, 0.51; 95% confidence interval, 0.32 to 0.81; p=0.005). Endoscopic ultrasound (EUS) identified detailed findings, especially the presence of septum (p

Background/Aims: Advanced biliary tract cancer (BTC) is associated with poor survival. A recent phase II study of triplet combination chemotherapy, including gemcitabine, cisplatin, and nanoparticle albumin-bound (nab)-paclitaxel, has shown promising results. This study aimed to compare the efficacy of triplet and standard doublet chemotherapy in a real-world setting. Methods: Patients with advanced BTC treated with triplet and doublet chemotherapy regimens were recruited. The propensity-score nearest neighbor matching method with a ratio of one-to-one was used to create a matched cohort for comparison. Progression-free survival (PFS), overall survival (OS), and safety profiles were examined in both groups. Results: A total of 68 patients (n=34 per group) were included in the matched cohort, and their baseline characteristics were well balanced. Survival outcomes in the triplet chemotherapy group were not better than those in the doublet chemotherapy group, with a median PFS of 7.5 months (95% confidence interval [CI], 4.1 to 10.9) versus 7.2 months (95% CI, 5.6 to 8.9) (hazard ratio [HR], 0.93; 95% CI, 0.53 to 1.62; p=0.793) and a median OS of 13.7 months (95% CI, 8.8 to 18.7) versus 12.2 months (95% CI, 8.4 to 16.0) (HR 0.73; 95% CI, 0.38 to 1.41; p=0.354), respectively. In addition, the treatment-related severe adverse events, such as neutropenia, were more common in the triplet chemotherapy group. Conclusions: Gemcitabine, cisplatin, and nab-paclitaxel did not improve the PFS or OS compared to that achieved by standard chemotherapy in patients with advanced BTC. The benefits of triplet chemotherapy in advanced BTC require examination in large randomized controlled trials.

Background/Aims Type 2 autoimmune pancreatitis (AIP) has been considered extremely rare in East Asia. This study aimed to clarify the prevalence, clinical characteristics and radiological findings of type 2 AIP highlighting patients presenting as acute pancreatitis in a single center. Methods : Type 2 AIP patients were classified according to International Consensus Diagnostic Criteria. Radiological findings were compared between type 2 AIP presenting as acute pancreatitis and gallstone pancreatitis. Results : Among 244 patients with AIP, 27 (11.1%) had type 2 AIP (definite, 15 [55.5%] and probable 12 [44.5%]). The median age of patients with type 2 AIP was 29 years (interquartile range, 20 to 39 years). Acute pancreatitis was the most common initial presentation (n=17, 63%) while obstructive jaundice was present in only one patient. Ulcerative colitis (UC) was associated with type 2 AIP in 44.4% (12/27) of patients. Radiological pancreatic imaging such as delayed enhancement of diffusely enlarged pancreas, homogeneous enhancement of focal enlargement/mass, absent/minimal peripancreatic fat infiltration or fluid collection, and multifocal main pancreatic duct narrowings were helpful for differentiating type 2 AIP from gallstone pancreatitis. During follow-up (median, 32.3 months), two patients (2/25, 8%) experienced relapse. Conclusion : s In South Korea, type 2 AIP is not as rare as previously thought. Overall, the clinical profile of type 2 AIP was similar to that of Western countries. Type 2 AIP should be considered in young UC patients with acute pancreatitis of uncertain etiology.

(1) Background: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an alternative treatment for pancreatic tumors. Currently, EUS-RFA has been trialled to treat hepatic tumors. However, little has been reported about optimal settings for EUS-RFA in patients with hepatic tumors. We evaluated the ablation effect after in vivo RFA using a new EUS-RFA electrode in a pig model. (2) Methods Four pigs were used for the in vivo test. The in vivo testing was divided into two tests based on the length of the RFA electrode (0.5, 0.7, 1 or 1.5 cm), the ablation power (30 W or 50 W), and the ablation time (10 or 15 s). In test one, ablation effect was evaluated based on the electrode length and power. In test two, ablation effect was assessed based on power and time. (3) Results: In test one, the ablation width and depth correlated with the length of the electrode and power (0.5 cm, 10 W, 10 s: width 0.46 cm, depth 0.65 cm vs. 1.5 cm, 75 W, 10 s: width 0.77 cm, depth 1.80 cm). In test two, ablation width and depth were similar when RFA was set at 1.5cm, 50 W, and 10 s or 1 cm, 30 W, and 15 s (0.65 cm, 1.14 cm vs. 0.65cm, 1.26 cm). (4) Conclusions: The relationship between electrode length, ablation power, and ablation time, and the resulting ablation effect in pig livers suggest that EUS-RFA produces effective ablation while minimizing thermal injury.

IntroductionFor unresectable hilar obstruction, restoring and maintaining biliary ductal patency are crucial for improved survival and quality of life. The endoscopic placement of stents is now a mainstay of its treatment, and bilateral stenting is effective for biliary decompression. This study aimed to determine the clinical outcomes of bilateral metal stent placement using large cell-type stents and the clinical predictors of stent dysfunction in patients with malignant hilar obstruction.MethodsWe performed a retrospective analysis of patients who underwent bilateral metal stent placement using two large cell-type stents at two academic teaching hospitals between September 2017 and February 2019. The primary outcome was stent dysfunction. Secondary outcomes included predictors related to stent dysfunction and overall survival.ResultsThe study included 87 patients who underwent bilateral metal stent placement for malignant hilar obstruction. Technical success and clinical success were achieved in 80 patients (92.0%) and 83 patients (95.4%), respectively. During the follow-up period (median: 201, range: 18-671 days), stent dysfunction occurred in 42 patients (48.3%), and the median stent patency was 199 days (95% confidence interval [CI]: 181-262). In univariate analysis, age, cholangitis before stent insertion, and subsequent chemotherapy were found to be associated with the cumulative risk of stent dysfunction. In multivariate analysis, cholangitis before stent insertion (hazards ratio [HR]: 2.26, 95% CI: 1.216-4.209, P = 0.010) and subsequent chemotherapy (HR: 0.250, 95% CI: 0.130-0.482, PConclusionThe bilateral placement of large cell-type stents for malignant hilar obstruction was effective with high technical and clinical success rates and acceptable patency. Cholangitis before stent insertion was associated with shorter patency, and subsequent chemotherapy was associated with longer stent patency.

Tetracera loureiri (T. loureiri) is a woody climber inhabiting open deciduous or evergreen forests in Southeast Asia. A decoction comprising its stem and other herbs is a traditional Thai remedy for fatigue and jaundice, as well as to promote overall health. Anti-inflammatory effects induced by T. loureiri extract have not been reported. In this study, we investigated the anti-inflammatory effect of an ethanol extract of T. loureiri (ETL) on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophages. We found that ETL treatment inhibited the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells, without affecting cell viability. The effect of ETL on the expression of various pro-inflammatory mediators was analyzed using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). We observed that ETL inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels and decreased the production of prostaglandin E2 (PGE2) by COX-2 in RAW264.7 macrophages. ETL dose-dependently reduced the production of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells, in a dose-dependent manner. Furthermore, ETL suppressed the LPS-induced nuclear translocation of the nuclear factor, NF-κB. Additionally, ETL was found to inhibit the activation of mitogen-activated protein kinases (MAPK), such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and p38 MAPK. In conclusion, our findings demonstrate that ETL inhibits the expression of pro-inflammatory mediators and cytokines, thereby downregulating NF-κB and MAPK signaling pathways in LPS-stimulated macrophages, Consequently, ETL is a potential therapeutic agent for the treatment of inflammatory diseases.

Abstract Background Endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) may facilitate tissue acquisition for a definitive diagnosis of gastrointestinal subepithelial tumors (SETs). This study aimed to determine the diagnostic yield of EUS-FNB using a novel 20-gauge ProCore needle with a coiled sheath in tissue sampling of gastrointestinal SETs. Methods Between July 2016 and February 2017, 39 patients with gastrointestinal SETs were prospectively recruited from six university hospitals in Korea. Hypoechoic SETs ≥2 cm in size and originating from the submucosal and/or muscularis propria layer under EUS were eligible. This study was registered on ClinicalTrials.gov (NCT02884154). Results A total of 36 patients were included in the final analyses. EUS-FNB was diagnostic in 88.9% of SETs. Tissue adequacy was judged as optimal in 97.2% of FNB specimens according to on-site visual evaluation by endosonographers, and in 88.9% of specimens according to pathologists. A macroscopically optimal core sample was obtained with two needle passes in 94.4% of cases. Technical failure rate was encountered in two cases (5.6%) after two needle passes. There were two cases (5.6%) of bleeding, which was managed endoscopically. Conclusions EUS-FNB using a 20-gauge ProCore needle is a technically feasible and effective modality for histopathologic diagnosis of gastrointestinal SETs, providing adequate core samples with fewer needle passes;ClinicalTrials.gov number, NCT02884154.

Background: Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy. Methods: BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing heterodimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation. Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

Preservation of muscle stem cell function is critical for muscle homeostasis and the regenerative capacity of stem cells declines with age, leading to muscle loss. Previously, daidzein, a natural isoflavone from Leguminosae, has been shown to prevent TNF-α-induced muscle atrophy. However, the molecular mechanisms of daidzein in these processes are currently unknown. In this study, we demonstrate a positive effect of black soybean extract (BS Ext) and daidzein on myoblast differentiation and myotube growth. Daidzein prevents dexamethasone-induced myotube atrophy through Akt activation. The promyogenic effect of BS Ext and daidzein is mediated through two promyogenic kinases, Akt and p38MAPK that in turn activates a key myogenic transcription factor MyoD. Additionally, BS Ext and daidzein promote myotube growth through Akt/mTOR/S6K pathway. Finally, daidzein augments MyoD-dependent myogenic conversion of mouse embryonic fibroblasts. Taken together, our data suggest that daidzein promotes myogenic differentiation and myotube hypertrophy through p38 and Akt/mTOR/S6K pathway.

Background: Ginsenoside Rg1 belongs to protopanaxatriol-type ginsenosides and has diverse pharmacological activities. In this report, we investigated whether Rg1 could upregulate muscular stem cell differentiation and muscle growth. Methods: C2C12 myoblasts, MyoD-transfected 10T1/2 embryonic fibroblasts, and HEK293T cells were treated with Rg1 and differentiated for 2 d, subjected to immunoblotting, immunocytochemistry, or immunoprecipitation. Results: Rg1 activated promyogenic kinases, p38MAPK (mitogen-activated protein kinase) and Akt signaling, that in turn promote the heterodimerization with MyoD and E proteins, resulting in enhancing myogenic differentiation. Through the activation of Akt/mammalian target of rapamycin pathway, Rg1 induced myotube growth and prevented dexamethasone-induced myotube atrophy. Furthermore, Rg1 increased MyoD-dependent myogenic conversion of fibroblast. Conclusion: Rg1 upregulates promyogenic kinases, especially Akt, resulting in improvement of myoblast differentiation and myotube growth.

PurposeStereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC.Patients and methodsWe retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24-36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed.ResultsA total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients.ConclusionsLAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia—a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Prevention of age-associated reduction in muscle mass and function is required to manage a healthy life. Supplemental (-)-Epicatechin (EC) appears to act as a potential regulator for muscle growth and strength. However, its cellular and molecular mechanisms as a potential muscle growth agent have not been studied well. In the current study, we investigated a role of EC in differentiation of muscle progenitors to gain the molecular insight into how EC regulates muscle growth. EC enhanced myogenic differentiation in a dose-dependent manner through stimulation of promyogenic signaling pathways, p38MAPK and Akt. EC treatment elevated MyoD activity by enhancing its heterodimerization with E protein. Consistently, EC also positively regulated myogenic conversion and differentiation of fibroblasts. In conclusion, EC has a potential as a therapeutic or nutraceutical remedy to treat degenerative muscle diseases or age-related muscle weakness.

Background: Although endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) with transmural stenting has increased for biliary decompression in patients with an inaccessible papilla, the optimal biliary access point and the learning curve of EUS-HGS have not been studied. We evaluated the optimal biliary access point and learning curve for technically successful EUS-HGS. Methods: 129 consecutive patients (male n = 81, 62.3%; malignant n = 113, 87.6%) who underwent EUS-HGS due to an inaccessible papilla were enrolled. EUS finding and procedure times according to each needle puncture attempt in EUS-HGS were prospectively measured. Learning curves of EUS-HGS were calculated for two main outcome measurements (procedure time and adverse events) by using the moving average method and cumulative sum (CUSUM) analysis, respectively. Results: A total of 174 EUS-HGS attempts were performed in 129 patients. The mean number of needle punctures was 1.35 ± 0.57. Using the logistic regression model, bile duct diameter of the puncture site ⩽ 5 mm [odds ratio (OR) 3.7, 95% confidence interval (CI): 1.71–8.1, p < 0.01] and hepatic portion length [linear distance from the mural wall to the punctured bile duct wall on EUS; mean hepatic portion length was 27 mm (range 10–47 mm)] > 3 cm (OR 5.7, 95% CI: 2.7–12, p < 0.01) were associated with low technical success. Procedure time and adverse events were shorter after 24 cases, and stabilized at 33 cases of EUS-HGS, respectively. Conclusions: Our data suggest that a bile duct diameter > 5 mm and hepatic portion length 1 cm to ⩽ 3 cm on EUS may be suitable for successful EUS-HGS. In our learning curve analysis, over 33 cases might be required to achieve the plateau phase for successful EUS-HGS.

Background/AimsRefeeding syndrome (RFS) is a fatal clinical complication that can occur as a result of fluid and electrolyte shifts during early nutritional rehabilitation for malnourished patients. This study was conducted to determine the clinical implications of RFS in patients with acute pancreatitis (AP).Methods : Between 2006 and 2016, AP patients with very early mortality were retrospectively enrolled from three university hospitals.Results : Among 3,206 patients with AP, 44 patients died within 3 days after diagnosis. The median age was 52.5 years (range, 27 to 92 years), male-to-female ratio was 3:1, and median duration from admission to death was 33 hours (range, 5 to 72 hours). The etiology of AP was alcohol abuse in 32 patients, gallstones in five patients, and hypertriglyceridemia in two patients. Ranson score, bedside index for severity of AP, and acute physiology and chronic health evaluation-II were valuable for predicting very early mortality (median, [range]; 5 [1 to 8], 3 [0 to 5], and 19 [4 to 45]). RFS was diagnosed in nine patients who died of septic shock (n=5), cardiogenic shock (n=2), or cardiac arrhythmia (n=2). In addition, patients with RFS had significant hypophosphatemia compared to non-RFS patients (2.6 mg/dL [1.3 to 5.1] vs 5.8 mg/dL [0.8 to 15.5]; p=0.001). The early AP-related mortality rate within 3 days was approximately 1.4%, and RFS occurred in 20.5% of these patients following sudden nutritional support.Conclusion : sThe findings of current study emphasize that clinicians should be aware of the possibility of RFS in malnourished AP patients with electrolyte imbalances.