Beyond the Bile: Exploring the Microbiome and Metabolites in Cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results. METHODS: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells. RESULTS: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis. CONCLUSIONS: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC.

ALK upregulates POSTN and WNT signaling to drive neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear. Here, we used a human stem cell-based model of neuroblastoma. Mis-expression of ALKF1174L and MYCN resulted in shorter latency compared to MYCN alone. MYCN tumors resembled adrenergic, while ALK/MYCN tumors resembled mesenchymal, neuroblastoma. Transcriptomic analysis revealed enrichment in focal adhesion signaling, particularly the extracellular matrix genes POSTN and FN1 in ALK/MYCN tumors. Patients with ALK-mutant tumors similarly demonstrated elevated levels of POSTN and FN1. Knockdown of POSTN, but not FN1, delayed adhesion and suppressed proliferation of ALK/MYCN tumors. Furthermore, loss of POSTN reduced ALK-dependent activation of WNT signaling. Reciprocally, inhibition of the WNT pathway reduced expression of POSTN and growth of ALK/MYCN tumor cells. Thus, ALK drives neuroblastoma in part through a feedforward loop between POSTN and WNT signaling.

Subcritical water-assisted fish gelatin hydrolysis for astaxanthin-loaded fish oil emulsion stability.

Though gelatin emulsifying properties have been intensively studied, how low-molecular-weight (LMW) fish gelatin affects astaxanthin (AST)-loaded fish oil emulsion stability remains elusive. In this study, subcritical water hydrolysis (SWH)-modified LMW fish gelatin (SWHG) was produced from 110 °C to 180 °C and used to enhance the AST steadiness in oil/water emulsions in the presence of an emulsifier, lecithin. In the prepared emulsions, the surface charge increased while droplet size decreased with the decrease in gelatin MW due to the reduced thickness of the adsorbed gelatin membrane. LMW gelatin and lecithin could form a firm-absorbed layer on the droplet surface by electrostatic interaction between amide groups of gelatin molecules and phosphate groups of lecithin, thus stabilizing the emulsions. SWHG improved the creaming stability of the emulsions and hindered the oxygen- and light-induced AST degradation for 11 months compared to high MW gelatin. Whereas, the control emulsion showed noticeable phase separation after two weeks of storage. These findings prove the advantage of the SWH approach and propose the use of SWHG in oil-in-water emulsions for AST stabilization.

Impact of the Supra-papilla Method on Patency in Distal Malignant Biliary Obstruction: A Multicenter Randomized Controlled Trial.

BACKGROUND: /aims: Placement of a self-expandable metal stent (SEMS) across the duodenal major papilla carries a risk of duodenobiliary reflux (DBR). The supra-papilla method of stenting may reduce DBR and improve stent patency compared to the trans-papilla method. This study aimed to compare the clinical outcomes between the supra-papilla and trans-papilla methods for distal malignant biliary obstruction (DMBO). METHODS: Between January 2021 and January 2023, consecutive patients with DMBO from six centers in Korea were randomly assigned to either the supra-papilla or trans-papilla method arm in a 1:1 ratio. The primary outcome was the duration of stent patency, and secondary outcomes included the cause of stent dysfunction, adverse events, and overall survival rate. RESULTS: A total of 84 patients were equally assigned to each group. The most common cause of DMBO was pancreatic cancer (n=50, 59.5%), followed by bile duct (n=20, 23.8%), gallbladder (n=11, 13.1%), and other cancers (n=3, 3.6%). Stent patency was significantly longer in the supra-papilla group (median [95% confidence interval], 369 [289-497] vs. 154 [78-361] days; P < 0.01). Development of DBR was significantly lower in the supra-papilla group (9.4% vs 40.8%, P < 0.01). Adverse events and overall survival rate were not significantly different between the two groups. CONCLUSIONS: The placement of SEMS using the supra-papilla method resulted in a significantly longer duration of stent patency. It is advisable to place the SEMS using the supra-papilla method in DMBO. Further studies with a larger number of patients are required to validate the benefits of the supra-papilla method.

Comparative efficacies and safeties of cylindrical interstitial laser ablation and radiofrequency ablation on swine pancreas.

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.

[Microbiome and Biliary Tract Cancer].

Biliary tract cancers encompass a group of malignancies that affect the bile ducts and gallbladder and are associated with a poor prognosis, often due to late diagnosis and limited treatment options. The incidence of biliary tract cancer has been increasing gradually, underscoring the need for a better understanding of its pathogenesis and potential risk factors. Research suggests that biliary tract cancer may develop through a combination of genetic and epigenetic alterations, as well as environmental factors. The role of microbial exposure and the human microbiome in the pathogenesis of biliary tract cancer is an emerging area of interest. Traditionally, the biliary tree was considered sterile under normal conditions, but recent studies have identified associations between specific microbiological patterns and inflammatory biliary diseases and cancer. The human microbiome plays a crucial role in maintaining host homeostasis and interacting with the host's immune system. Dysbiosis, or an imbalance in the microbiome composition, has been implicated in the development of various diseases, including cancer. Hence, dysbiosis in the biliary tract might trigger the pathogenesis of biliary tract cancer. Advances in next-generation sequencing technology have provided researchers with a more comprehensive view of the microbiota and their potential roles in health and disease, providing more evidence of the relationship between the microbiota and biliary tract cancer. This review summarizes the latest evidence of the microbiome that would be associated with biliary tract cancer.

Optimization and evaluation of Atrina pectinata polysaccharides recovered by subcritical water extraction: A promising path to natural products.

In this study, the recovery of Atrina pectinata posterior adductor polysaccharides (APP-PS) using subcritical water extraction (SWE) was optimized by response surface methodology (RSM) and the physicochemical and biological properties of the recovered APP-PS were evaluated. The optimal extraction conditions, which resulted in a maximum yield of 55.58 ± 1.12 %, were temperature, 152.08 °C; extraction time, 10 min; solid-liquid ratio, 30 g/600 mL. The obtained APP-PS was found to be 88.05 ± 0.17 % total sugar. Fourier transform infrared (FT-IR) and Nuclear magnetic resonance (NMR) analyses confirmed the presence of the α-coordination of D-glucan in the polymer sample. The analysis of monosaccharide composition, along with thermogravimetric analysis, revealed the typical structure of the sample, composed of glucose alone. Total phenolic contents of APP-PS were measured as 5.47 ± 0.01 mg Gallic acid/g of dry sample and total flavonoids contents were determined to be 0.78 ± 0.06 mg Quercetin/g of dry sample. For biological activities, ABTS+, DPPH and FRAP antioxidant activities were measured to be 20.00 ± 0.71, 2.35 ± 0.05 and 4.02 ± 0.07 µg Trolox equivalent/100 g of dry sample, respectively. Additionally ACE inhibitory was confirmed to be 87.02 ± 0.47 %. These results showed that SWE is an effective method to recover biofunctional materials from marine organisms.

Dielectrophoretic Capture of Cancer-Derived Small-Extracellular-Vesicle-Bound Janus Nanoparticles via Lectin-Glycan Interaction.

Glycosylation is closely related to cellular metabolism and disease progression. In particular, glycan levels in cancer cells and tissues increase during cancer progression. This upregulation of glycosylation in cancer cells may provide a basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. Here, they developed a detection technology for pancreatic cancer cell-derived small extracellular vesicles (PC-sEVs) based on lectin-glycan interactions. Lectins specific for sialic acids are conjugated to Janus nanoparticles to induce interactions with PC-sEVs in a dielectrophoretic (DEP) system. PC-sEVs are selectively bound to the lectin-conjugated Janus nanoparticles (lectin-JNPs) with an affinity comparable to that of conventionally used carbohydrate antigen 19-9 (CA19-9) antibodies. Furthermore, sEVs-bound Lectin-JNPs (sEVs-Lec-JNPs) are manipulated between two electrodes to which an AC signal is applied for DEP capture. In addition, the proposed DEP system can be used to trap the sEVs-Lec-JNP on the electrodes. Their results, which are confirmed by lectin-JNPs using the proposed DEP system followed by target gene analysis, provide a basis for the development of a new early diagnostic marker based on the glycan characteristics of PC-sEVs. In turn, these novel detection methods could overcome the shortcomings of commercially available pancreatic cancer detection techniques.

Clinical correlation of cholelithiasis in patients undergoing percutaneous endoscopic gastrostomy.

The risk factor for cholelithiasis include low physical activity. With an aging society, the number of bedridden patients who undergo percutaneous endoscopic gastrostomy (PEG) has increased, and cholelithiasis has often been found in these patients. This study aimed to evaluate the risk factors correlated with cholelithiasis in adults who underwent PEG. This retrospective single-center design study reviewed patients who underwent PEG and were confirmed to have cholelithiasis through imaging from March 1996 to December 2021. The investigated variables were age, sex, body mass index (BMI, kg/m2), cause of PEG insertion, initial physical activity status, laboratory findings on PEG insertion day, and incidence of acute cholecystitis. The differences between categorical and continuous variables were analyzed using Student's t test and chi-square test. We enrolled 576 eligible patients who underwent PEG insertion. A total of 161 patients were detected with cholelithiasis (28.0%). The overall independent risk factors for cholelithiasis in patients who underwent PEG insertion were increased C-reactive protein (CRP) levels and decreased physical activity status (bedridden state). The incidence of cholelithiasis was increased by up to 30.7%, especially in patients with bedridden status. However, the incidence of acute cholecystitis among cholelithiasis group was only 5.6%. BMI and total cholesterol were positively correlated with the size of gallbladder (GB) stones. One of the major risk factors for cholelithiasis is decreased physical activity, especially in patients who underwent PEG insertion. Abdominal imaging is recommended to confirm the presence of cholelithiasis and to consider prophylaxis for cholelithiasis, especially in bedridden patients with elevated initial CRP levels at the time of PEG insertion.

Anti-CCL2 antibody combined with etoposide prolongs survival in a minimal residual disease mouse model of neuroblastoma.

C-C motif chemokine ligand 2 (CCL2) is a monocyte chemoattractant that promotes metastatic disease and portends a poor prognosis in many cancers. To determine the potential of anti-CCL2 inhibition as a therapy for recurrent metastatic disease in neuroblastoma, a mouse model of minimal residual disease was utilized in which residual disease was treated with anti-CCL2 monoclonal antibody with etoposide. The effect of anti-CCL2 antibody on neuroblastoma cells was determined in vitro with cell proliferation, transwell migration, and 2-dimensional chemotaxis migration assays. The in vivo efficacy of anti-CCL2 antibody and etoposide against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice. In vitro, anti-CCL2 antibody did not affect cell proliferation but significantly inhibited neuroblastoma cell and monocyte migration towards an increasing CCL2 concentration gradient. Treatment of mice with anti-CCL2 antibody combined with etoposide significantly increased survival of mice after resection of primary tumors, compared to untreated mice.

Prognostic Impact of Minimal Pelvic Fluid in Locally Advanced Pancreatic Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Minimal pelvic fluid (MPF) is occasionally encountered on computed tomography (CT) scans during the initial staging of newly diagnosed pancreatic cancer. However, its clinical relevance has scarcely been studied. This study intends to explore the incidence of minimal pelvic fluid and its relevance in terms of survival in locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: The medical records of patients with LAPC at 4 tertiary referral institutions were retrospectively reviewed from January 2005 to December 2015. Minimal pelvic fluid was defined as a fluid collection volume in the pelvic cavity of <100 mL as determined by abdominal CT. The association between the presence of MPF and patient survival was evaluated. RESULTS: A total of 59 patients (male:female, 33:26; median age, 68 years; range 46-82 years) with LAPC were enrolled. Of the 59 patients, 22.0% (n = 13) had MPF, and 78.0% (n = 46) had no pelvic fluid (NPF). Baseline clinical characteristics in the 2 groups, including extent of the tumor stage, extent of spread to the lymph nodes stage, and pattern of treatments, were not significantly different. However, median overall survival was significantly less in the MPF group [9.7 months, (95% CI, 5.9-13.5)] than in the NPF group as determined by the log-rank test [16.9 months, (95% CI, 9.3-24.5)] (P = .002), and univariate and multivariate analyses showed that the presence of MPF independently predicted a poor prognosis. CONCLUSION: The presence of MPF was found to be significantly associated with reduced survival and an independent poor prognostic biomarker in LAPC patients.

Trash to Treasure: An Up-to-Date Understanding of the Valorization of Seafood By-Products, Targeting the Major Bioactive Compounds.

Fishery production is exponentially growing, and its by-products negatively impact industries' economic and environmental status. The large amount of bioactive micro- and macromolecules in fishery by-products, including lipids, proteins, peptides, amino acids, vitamins, carotenoids, enzymes, collagen, gelatin, chitin, chitosan, and fucoidan, need to be utilized through effective strategies and proper management. Due to the bioactive and healthy compounds in fishery discards, these components can be used as functional food ingredients. Fishery discards have inorganic or organic value to add to or implement in various sectors (such as the agriculture, medical, and pharmaceutical industries). However, the best use of these postharvest raw materials for human welfare remains unelucidated in the scientific community. This review article describes the most useful techniques and methods, such as obtaining proteins and peptides, fatty acids, enzymes, minerals, and carotenoids, as well as collagen, gelatin, and polysaccharides such as chitin-chitosan and fucoidan, to ensure the best use of fishery discards. Marine-derived bioactive compounds have biological activities, such as antioxidant, anticancer, antidiabetic, anti-inflammatory, and antimicrobial activities. These high-value compounds are used in various industrial sectors, such as the food and cosmetic industries, owing to their unique functional and characteristic structures. This study aimed to determine the gap between misused fishery discards and their effects on the environment and create awareness for the complete valorization of fishery discards, targeting a sustainable world.

Segmentation algorithm can be used for detecting hepatic fibrosis in SD rat.

BACKGROUND: Liver fibrosis is an early stage of liver cirrhosis. As a reversible lesion before cirrhosis, liver failure, and liver cancer, it has been a target for drug discovery. Many antifibrotic candidates have shown promising results in experimental animal models; however, due to adverse clinical reactions, most antifibrotic agents are still preclinical. Therefore, rodent models have been used to examine the histopathological differences between the control and treatment groups to evaluate the efficacy of anti-fibrotic agents in non-clinical research. In addition, with improvements in digital image analysis incorporating artificial intelligence (AI), a few researchers have developed an automated quantification of fibrosis. However, the performance of multiple deep learning algorithms for the optimal quantification of hepatic fibrosis has not been evaluated. Here, we investigated three different localization algorithms, mask R-CNN, DeepLabV3+, and SSD, to detect hepatic fibrosis. RESULTS: 5750 images with 7503 annotations were trained using the three algorithms, and the model performance was evaluated in large-scale images and compared to the training images. The results showed that the precision values were comparable among the algorithms. However, there was a gap in the recall, leading to a difference in model accuracy. The mask R-CNN outperformed the recall value (0.93) and showed the closest prediction results to the annotation for detecting hepatic fibrosis among the algorithms. DeepLabV3+ also showed good performance; however, it had limitations in the misprediction of hepatic fibrosis as inflammatory cells and connective tissue. The trained SSD showed the lowest performance and was limited in predicting hepatic fibrosis compared to the other algorithms because of its low recall value (0.75). CONCLUSIONS: We suggest it would be a more useful tool to apply segmentation algorithms in implementing AI algorithms to predict hepatic fibrosis in non-clinical studies.

Long-term survival benefits of intrathecal autologous bone marrow-derived mesenchymal stem cells (Neuronata-R®: lenzumestrocel) treatment in ALS: Propensity-score-matched control, surveillance study.

Objective: Neuronata-R® (lenzumestrocel) is an autologous bone marrow-derived mesenchymal stem cell (BM-MSC) product, which was conditionally approved by the Korean Ministry of Food and Drug Safety (KMFDS, Republic of Korea) in 2013 for the treatment of amyotrophic lateral sclerosis (ALS). In the present study, we aimed to investigate the long-term survival benefits of treatment with intrathecal lenzumestrocel. Methods: A total of 157 participants who received lenzumestrocel and whose symptom duration was less than 2 years were included in the analysis (BM-MSC group). The survival data of placebo participants from the Pooled-Resource Open-Access ALS Clinical Trials (PROACT) database were used as the external control, and propensity score matching (PSM) was used to reduce confounding biases in baseline characteristics. Adverse events were recorded during the entire follow-up period after the first treatment. Results: Survival probability was significantly higher in the BM-MSC group compared to the external control group from the PROACT database (log-rank, p < 0.001). Multivariate Cox proportional hazard analysis showed a significantly lower hazard ratio for death in the BM-MSC group and indicated that multiple injections were more effective. Additionally, there were no serious adverse drug reactions found during the safety assessment, lasting a year after the first administration. Conclusion: The results of the present study showed that lenzumestrocel treatment had a long-term survival benefit in real-world ALS patients.

Efficacy Analysis of Suprapapillary versus Transpapillary Self-Expandable Metal Stents According to the Level of Obstruction in Malignant Extrahepatic Biliary Obstruction.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS. Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively. Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV. Conclusions: The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

Development of fish gelatin/carrageenan/zein bio-nanocomposite active-films incorporated with turmeric essential oil and their application in chicken meat preservation.

Gelatin/carrageenan (Ge/Car) active packaging films incorporated with turmeric essential oil (TEO) encapsulated in zein nanoparticles (ZNP) were developed. The efficacy of these active packaging films and their antimicrobial properties were also investigated to ensure their practical application. Three different types of nanocomposite films (Ge/Car, Ge/Car/TEO, and Ge/Car/ZNP) were prepared. The characterization of the films was elucidated using Fourier transform infrared (FTIR), X-ray diffraction analyses (XRD), and scanning electron microscope (SEM). Physicochemical and mechanical properties of the films were enhanced, owing to the application of TEO-containing nanocomposites. Supercritical-CO2 extracted TEO showed excellent biological activities, alongside GC-MS analysis identified that TEO contained 33 bioactive compounds where the major constituent was Zingiberene. ZNP proved an excellent carrier of TEO. The nanocomposite film sustainably released TEO, improving the shelf life of the chicken meat by reducing bacterial colonies from 3.08 log CFU/g to 2.81 log CFU/g after 14 days incubation against Salmonella enterica compared with 6.66 log CFU/g observed in the control film. The overall results of this study suggest that the nanocomposite active film is an excellent candidate for food packaging to ensure a better world.

Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. METHODS: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. RESULTS: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. CONCLUSION: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.

Current Practice Patterns of Endoscopic Ultrasound-Guided Tissue Sampling for Pancreatic Solid Mass in Korea: Outcomes of a National Survey.

Background/Aims: Although endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) are widely used for tissue acquisition of pancreatic solid mass, the optimal strategy of this procedure has not been established yet. The aim of this nationwide study was to investigate the current practice patterns of EUS-FNA/FNB for pancreatic solid mass in Korea. Methods: The Policy-Quality Management of the Korean Pancreatobiliary Association (KPBA) developed a questionnaire containing 22 questions. An electronic survey consisting of the questionnaire was distributed by e-mail to members registered to the KPBA. Results: A total of 101 respondents completed the survey. Eighty respondents (79.2%) performed preoperative EUS-FNA/FNB for operable pancreatic solid mass. Acquire needles (60.4%) were used the most, followed by ProCore needles (47.5%). In terms of need size, most respondents (>80%) preferred 22-gauge needles regardless of the location of the mass. Negative suction with a 10-mL syringe (71.3%) as sampling technique was followed by stylet slow-pull (41.6%). More than three needle passes for EUS-FNA/FNB was performed by most respondents (>80%). The frequency of requiring repeated procedure was significantly higher in respondents with a low individual volume (<5 per month, p=0.001). Prophylactic antibiotics were routinely used in 39 respondents (38.6%); rapid on-site pathologic evaluation was used in 6.1%. Conclusions: According to this survey, practices of EUS-FNA/FNB for pancreatic solid mass varied substantially, some of which differed considerably from the recommendations present in existing guidelines. These results suggest that the development of evidence-based quality guidelines fitting Korean clinical practice is needed to establish the optimal strategy for this procedure.

Endoscopic Ultrasound-Guided Pancreatic Interstitial Laser Ablation Using a Cylindrical Laser Diffuser: A Long-Term Follow-Up Study.

BACKGROUND AND AIMS: Local ablative treatment is another option for improving outcomes and has been evaluated for locally advanced pancreatic cancer. We previously suggested endoscopic ultrasound (EUS)-guided interstitial laser ablation using a cylindrical laser diffuser (CILA) might be a feasible therapeutic option based on experiments performed on pancreatic cancer cell lines and porcine model with a short follow-up (3 days). The aim of this study was to investigate the safety of EUS-CILA performed using optimal settings in porcine pancreas with a long-term follow-up (2 weeks). METHODS: EUS-CILA (laser energy of 450 J; 5 W for 90 s) was applied to normal pancreatic tissue in porcine (n = 5) under EUS guidance. Animals were observed clinically for 2 weeks after EUS-CILA to evaluate complications. Computed tomography and laboratory tests were carried out to evaluate safety. Two weeks after EUS-CILA, all pigs were sacrificed, and histopathological safety and efficacy evaluations were conducted. RESULTS: EUS-CILA was technically successful in all five cases. No major complications occurred during the follow-up period. Body weight of porcine did not change during the study period without any significant change in feed intake. Animals remained in excellent condition throughout the experimental period, and laboratory tests and computed tomography (CT) scans provided no evidence of a major complication. Histopathological evaluation showed complete ablation in the ablated area with clear delineation of surrounding normal pancreatic tissue. Mean ablated volume was 55.5 mm2 × 29.0 mm and mean ablated areas in the pancreatic sections of the five pigs were not significantly different (p = 0.368). CONCLUSIONS: In conclusion, our experimental study suggests that EUS-CILA is safe and has the potential to be an effective local treatment modality. No major morbidity or mortality occurred during the study period. Further evaluations are warranted before clinical application.

Effect of a Proton Pump Inhibitor on the Duodenum Microbiome of Gastric Ulcer Patients.

The gut microbiota are regarded as a functional organ that plays a substantial role in human health and disease. Proton pump inhibitors (PPIs) are widely used in medicine but can induce changes in the overall gut microbiome and cause disease-associated dysbiosis. The microbiome of the duodenum has not been sufficiently studied, and the effects of PPIs on the duodenal microbiome are poorly understood. In this study, we investigated the effect of PPI administration on duodenum microbiota in patients with a gastric ulcer. A total of 12 gastric ulcer patients were included, and PPI (Ilaprazole, Noltec®, 10 mg) was prescribed in all patients for 4 weeks. A total of 17 samples from the second portion of the duodenum were analyzed. Microbiome compositions were assessed by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). Changes in microbiota compositions after 4 weeks of PPI treatment were analyzed. a-Diversity was higher after PPI treatment (p = 0.02, at Chao1 index), and ß-diversity was significantly different after treatment (p = 0.007). Welch's t-test was used to investigate changes in phyla, genus, and species level, and the abundance of Akkermansia muciniphila, belonging to the phylum Verrucomicrobia, and Porphyromonas endodontalis, belonging to the phylum Bacteroidetes, was significantly increased after treatment (p = 0.044 and 0.05). PPI administration appears to induce duodenal microbiome dysbiosis while healing gastric ulcers. Further large-scale studies on the effects of PPIs on the duodenal microbiome are required.