Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer.

BACKGROUND & AIMS: Recent advances in molecular profiling enable the identification of potential therapeutic targets for biliary tract cancer (BTC). However, in patients with BTC, molecular profiling is hindered by challenges in obtaining adequate tissue samples. Circulating tumor DNA (ctDNA) may offer an alternative to tissue-based analysis. Here we aimed to assess the concordance between ctDNA and tissue genomic profiling in a large cohort of Asian patients with advanced BTC, and to evaluate the feasibility of liquid biopsy in BTC treatment. METHODS: This study included patients with systemic treatment-naive advanced BTC, treated at CHA Bundang Medical Center between January 2019 and December 2022. We enrolled patients with available baseline tissue-based next-generation sequencing (NGS), and sufficient plasma samples for ctDNA analysis (AlphaLiquid®100 from IMBdx). RESULTS: Among 102 enrolled patients, 49.0% had intrahepatic cholangiocarcinoma, 26.5% extrahepatic cholangiocarcinoma, and 24.5% gallbladder cancer. The concordance between intra-patient ctDNA and tumor tissue mutations revealed a sensitivity of 84.8%, and positive predictive value of 79.4%. ctDNA revealed targetable alterations in 34.3% of patients-including FGFR2 fusion, IDH1 mutation, microsatellite instability (MSI)-high, ERBB2 amplification, PIK3CA mutations, BRCA1/2 mutations, and MET amplification. Notably, a novel FGFR2-TNS1 fusion was identified in ctDNA, which was not targeted in the tissue NGS panel. A high maximum somatic variant allele frequency in ctDNA was associated with poor prognosis after gemcitabine/cisplatin-based chemotherapy, in terms of both overall survival (p = 6.9 × 10-6) and progression-free survival (p = 3.8 × 10-7). CONCLUSIONS: Among patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC. IMPACT AND IMPLICATIONS: Our study is the first large-scale investigation of the clinical utility of liquid biopsy, focusing on ctDNA, as an alternative to conventional tumor tissue analysis, among Asian patients with advanced BTC. The results demonstrated acceptable concordance between analysis of ctDNA versus tissue for identifying therapeutic targets and potentially actionable genetic alterations. This indicates that ctDNA analysis can provide critical insights regarding advanced BTC treatment, particularly in cases where it is challenging to obtain or analyze tumor tissue.

Band-selective gap opening by a C 4-symmetric order in a proximity-coupled heterostructure Sr2VO3FeAs.

Complex electronic phases in strongly correlated electron systems are manifested by broken symmetries in the low-energy electronic states. Some mysterious phases, however, exhibit intriguing energy gap opening without an apparent signature of symmetry breaking (e.g., high-TC cuprates and heavy fermion superconductors). Here, we report an unconventional gap opening in a heterostructured, iron-based superconductor Sr2VO3FeAs across a phase transition at T 0 ∼150 K. Using angle-resolved photoemission spectroscopy, we identify that a fully isotropic gap opens selectively on one of the Fermi surfaces with finite warping along the interlayer direction. This band selectivity is incompatible with conventional gap opening mechanisms associated with symmetry breaking. These findings, together with the unusual field-dependent magnetoresistance, suggest that the Kondo-type proximity coupling of itinerant Fe electrons to localized V spin plays a role in stabilizing the exotic phase, which may serve as a distinct precursor state for unconventional superconductivity.

Mechanistic loop resolution strategy for short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y reconstruction after gastrectomy (with video).

BACKGROUND: Endoscopic access to the targeted site is a major challenge for the endoscopic retrograde cholangiopancreatography (ERCP) in patients undergoing Roux-en-Y (R-Y) reconstruction after total or subtotal gastrectomy. We aimed to evaluate the feasibility, reproducibility, and safety of mechanistic loop resolution strategies using a short-type single-balloon enteroscopy (short SBE) system. METHODS: Between February 2020 and March 2022, consecutive patients with a previous R-Y gastrectomy requiring ERCP were prospectively enrolled. Different mechanistic loop resolution strategies for two-dimensional loops, three-dimensionally rotated loops, and loops making a cane or S-shape were applied during the SBE approach. RESULTS: Forty-three short SBE-ERCP procedures were performed on 37 patients, with an approach success rate of 100.0% (43/43). The mean time to reach the jejunojejunal anastomosis and target site were 8.0 (6.0-11.0) minutes and 26.0 (16.0-36.0) minutes, respectively. The major challenges for the approach were the cane or S-shaped loop in the jejunojejunal anastomosis or Treitz ligament. The retroflex positioning of a SBE in front of the papilla was achieved in 86.0% (37/43), and the cannulation success rate in patients with an intact papilla was 90.9% (30/33). The initial, overall therapeutic successes, median total procedure time, and adverse event rate were 87.8%, 92.7%, 77.0 (IQR 56-100.5) minutes, and 11.6%, respectively. CONCLUSIONS: Short SBE-ERCP using standardized mechanistic loop resolution strategies is effective and reproducible in patients with R-Y reconstruction after gastrectomy. TRIAL REGISTRATION: ClinicalTrial.gov (NCT04847167).

Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study.

BACKGROUND AND AIMS: Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. METHODS: During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. RESULTS: In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P < .0001). CONCLUSIONS: The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).

Can prophylactic argon plasma coagulation reduce delayed post-papillectomy bleeding? A prospective multicenter trial.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed post-papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy. METHODS: In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow-up duodenoscopy to identify post-papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post-papillectomy bleeding rate and the tumor persistence rate. RESULTS: The delayed post-papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non-APC group (P = 0.434). The post-procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure-related mortalities or serious complications. CONCLUSION: Prophylactic APC may not be effective in reducing delayed post-papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration-cris.nih.go.kr; KCT0001955).

Mechanical properties and degradation process of biliary self-expandable biodegradable stents.

OBJECTIVES: The clinical outcomes and prevalence of adverse events associated with biliary biodegradable stents (BS) can differ according to degradation process and time. The aim of this study was to observe the degradation process and time of different BS prototypes, and to evaluate sequential changes in their mechanical properties. METHODS: Using an in vitro bile flow phantom model, we compared degradation time, radial force changes, and morphologic changes among four different BS prototypes: polydioxanone (PDO) BS, polyglycolide (PGA) BS, polydioxanone/poly-l-lactic acid (PDO/PLLA) sheath-core BS, and polydioxaone/magnesium (PDO/Mg) sheath-core BS. Using an in vivo swine bile duct dilation model, we performed a direct peroral cholangioscopy (DPOC) examination to observe the biodegradation process and related adverse events at regular intervals. RESULTS: In the bile flow phantom model, the PGA BS and PDO/Mg BS prototypes showed rapid radial force reduction and morphological changes and complete degradation within six weeks. PDO/PLLA BS maintained high radial force and kept their original shape for longer than the PDO BS, up to 16 weeks. A total of 24 BS were inserted into the dilated bile ducts of 12 swine. In this animal model, DPOC examination revealed that PDO BS and PDO/PLLA BS maintained their original shapes for approximately 12 weeks, but PDO BS showed a greater degree of fragmentation and induced biliary stones and bile duct obstruction. CONCLUSION: Our results showed that PDO/PLLA BS maintained their original shape and radial force for a relatively long time and minimized adverse events.

Primary Needle-Knife Fistulotomy Versus Conventional Cannulation Method in a High-Risk Cohort of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

OBJECTIVES: Successful biliary cannulation is a prerequisite and important component of endoscopic retrograde cholangiopancreatography, but conventional cannulation methods (CCMs) have a postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) rate of 14.1% in patients at high risk for PEP. The aim of this study was to evaluate the effectiveness and safety of needle-knife fistulotomy (NKF), compared with a CCM, when used for primary biliary access in patients at high risk for developing PEP. METHODS: A total of 207 patients with one or more risk factors for PEP were prospectively enrolled. The patients were randomly allocated to one of 2 groups according to the primary biliary cannulation technique (NKF or CCM). We compared biliary cannulation success rates, cannulation and procedure times, and the incidence of adverse events, including PEP, between the groups. RESULTS: The mean number of PEP risk factors was similar between the groups (NKF, 2.2 ± 1.0; CCM, 2.2 ± 0.9). PEP occurred in 8 patients in the CCM group and in no patients in the NKF group (9.2% vs 0%, P < 0.001). The rates of other adverse events did not differ between the groups. The biliary cannulation success rate was high in the NKF group, but relatively low in the CCM group, possibly because of the stringent failure criteria aimed at reducing PEP. However, the mean cannulation and total procedural times were longer in the NKF group than in the CCM group. DISCUSSION: NKF is an effective and safe procedure to gain primary biliary access in patients at high risk for developing PEP. ClinicalTrials.gov, NCT02916199.

Utility of EUS elastography in the diagnosis of gastric subepithelial tumors: a pilot study (with video).

BACKGROUND AND AIMS: EUS elastography is a real-time imaging technique that analyzes tissue elasticity. The aim of this study was to investigate the applicability of quantitative EUS elastography in the differential diagnosis of gastric subepithelial tumors (SETs). METHODS: We prospectively registered 41 consecutive patients with gastric SETs and measured their strain ratios with EUS elastography. The strain ratios of gastric SETs were compared with the histopathologic diagnosis. RESULTS: Thirty-one patients (mean age, 51.4 ± 12.6 years) were included in the analysis. The mean size of the SETs was 2.3 ± 0.7 cm. Lipomas had the lowest strain ratio of 1.6 (1.1-2.0), followed by leiomyomas 6.0 (2.0-29.0), ectopic pancreas 11.8 (1.7-29.3), gastrointestinal stromal tumors (GISTs) 51.1 (29.0-67.0), and schwannomas 62.0. With a cut-off value of 22.7, EUS elastography could differentiate GISTs from leiomyomas with sensitivity and specificity of 100% and 94.1%, respectively (P = .001; 95% confidence interval, 0.979-1.000). CONCLUSIONS: EUS elastography could be a promising diagnostic adjunct for the assessment of gastric SETs, especially in differentiating GISTs from leiomyomas.

Production of ERCP training model using a 3D printing technique (with video).

BACKGROUND: ERCP training models are very different in terms of anatomical differences, ethical issues, storage problems, realistic tactile sensation, durability and portability. There is no easy way to select an optimized model for ERCP training. If the ERCP training model could be made as a soft silicone model using 3D printing technique, it would have numerous advantages over the models presented so far. The purpose of this study was to develop an optimized ERCP training model using a 3D printing technique and to try to find ways for implementing various practical techniques. METHODS: All organ parts of this model were fabricated using silicone molding techniques with 3D printing. Especially, various anatomy of the ampulla of Vater and common bile duct (CBD) were creatively designed for different diagnostic and therapeutic procedures. In order to manufacture each of the designed organ parts with silicone, a negative part had to be newly designed to produce the molder. The negative molders were 3D printed and then injection molding was applied to obtain organ parts in silicone material. The eight different types of ampulla and CBD were repeatedly utilized and replaced to the main system as a module-type. RESULTS: ERCP training silicone model using 3D technique was semi-permanently used to repeat various ERCP procedures. All ERCP procedures using this model could be observed by real-time fluoroscopic examination as well as endoscopic examination simultaneously. Using different ampulla and CBD modules, basic biliary cannulation, difficult cannulation, stone extraction, mechanical lithotripsy, metal stent insertion, plastic stent insertion, and balloon dilation were successfully and repeatedly achieved. Endoscopic sphincterotomy was also performed on a specialized ampulla using a Vienna sausage. After repeat procedures and trainings, all parts of organs including the ampulla and CBD modules were not markedly damaged or deformed. CONCLUSIONS: We made a specialized ERCP training silicon model with 3D printing technique. This model is durable, relatively cheap and easy to make, and thus allows the users to perform various specialized ERCP techniques, which increases its chances of being a good ERCP training model.

Efficacy of a modified double-guidewire technique using an uneven double lumen cannula (uneven method) in patients with surgically altered gastrointestinal anatomy (with video).

BACKGROUND: Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) has been reported to be effective for patients with surgically altered gastrointestinal anatomy. However, selective biliary cannulation remains difficult in BE-ERCP. We examined the usefulness of a modified double-guidewire technique using an uneven double lumen cannula (the uneven method) for BE-ERCP in patients with surgically altered gastrointestinal anatomy. METHODS: To clarify the usefulness of the uneven method for selective biliary cannulation in BE-ERCP in comparison to the pancreatic guidewire (PGW) method, 40 patients with surgically altered gastrointestinal anatomy who underwent BE-ERCP with successful placement of a guidewire in the pancreatic duct were evaluated. The uneven method was used in 18 cases (uneven group) and the PGW method was used in the remaining 22 cases (PGW group). RESULTS: The technical success rate of biliary cannulation was higher in the uneven group than in the PGW group (83.3 vs. 59.0%; P = 0.165). In addition, the time to biliary cannulation were significantly shorter in the uneven group than in the PGW group (6 vs. 18 min; P = 0.004; respectively). In the PGW group, post-ERCP pancreatitis (PEP) occurred in 3 of 22 cases (13.6%). No adverse events, including PEP, occurred in the uneven group. CONCLUSIONS: The uneven method may be a useful option of selective biliary cannulation in BE-ERCP for the patients with surgically altered gastrointestinal anatomy.

Electrical Tuning of the Excitonic Insulator Ground State of Ta_{2}NiSe_{5}.

We demonstrate that the excitonic insulator ground state of Ta_{2}NiSe_{5} can be electrically controlled by electropositive surface adsorbates. Our studies utilizing angle-resolved photoemission spectroscopy reveal intriguing wave-vector-dependent deformations of the characteristic flattop valence band of this material upon potassium adsorption. The observed band deformation indicates a reduction of the single-particle band gap due to the Stark effect near the surface. The present study provides the foundation for the electrical tuning of the many-body quantum states in excitonic insulators.

Evaluation of valve function in antireflux biliary metal stents.

BACKGROUND: To overcome duodenobiliary reflux induced by biliary stents, antireflux valve (ARV) biliary stents have been developed and showed improvement in stent patency. However, negative study results have also been reported because stent patency may be decreased by the malfunction of ARV itself. Given such mixed results, the true efficacy of ARV remains unknown and the mechanism of its dysfunction needs to be clearly elucidated. The aim of this study was to investigate the exact mechanism of ARV dysfunction using in vitro phantom models. METHODS: Two experimental models were designed to evaluate two important environmental factors suspected to cause ARV malfunction, i.e. bile flow and pH. Three types of ARV metal stents from different companies were used for the experiments: a funnel type ARV, a windsock type ARV, and a wine glass-shaped ARV. Ten stents of each type were tested (five stents in the bile flow phantom model, and another five stents in the duodenal pH environmental model). To determine ARV malfunction, ARV-induced flow resistance was measured using a custom-made testing device. All stents from the two models were removed every 2 weeks for 12 weeks after stent insertion and were evaluated on morphological and functional changes of the ARV. RESULTS: Only ARV of wine glass-shaped ARV was morphologically changed due to silicone bond detachment in the bile flow model. All types of ARV were morphologically changed in the pH model. The morphological changes of ARV influenced the flow resistance. The antegrade pressure gradients were increased over time in the pH model (p < 0.05). CONCLUSIONS: Morphological change of the ARVs may induce dysfunction of ARV metal stents, which is mainly due to duodenal pH environment. In the future, development of new ARV that is not affected by duodenal environmental factors can be expected to improve stent patency.

Experimental study on the friction effect of plastic stents for biliary stone fragmentation (with video).

BACKGROUND AND AIM: In patients with irretrievable or intractable bile duct stone, temporary insertion of a plastic stent (PS) followed by further endoscopic retrograde cholangiopancreatography (ERCP) or surgery has been recommended as a 'bridge' therapy. However, the exact mechanism of stone fragmentation has not been discovered. The aim of the present study was to evaluate whether PS shape can facilitate stone fragmentation. METHODS: Using a new in vitro bile flow phantom model, we compared the friction effect among three different PS groups (straight PS group, double pigtail-shaped PS group, and screw-shaped PS group) and a control group. Each group had 10 silicon tube blocks that separately contained one stone and two PS. The control group had 10 blocks each with only a stone and no PS. We carried out analysis of the friction effect by stone weight and volume changes among the groups, excluding fragmented stones. RESULTS: After 8 weeks, complete fragmentation was noted in one out of 34 cholesterol stones (2.9%) and in four out of six pigmented stones (66.7%). Fragmentation tended to be more prominent in the screw-shaped PS group than in the straight PS group, double pigtail-shaped group, and control group (volume change: -11.33%, 7.94%, 4.43%, and 2.05%, respectively, P = 0.1390; weight change: -9.30%, 0.71%, -0.10%, and -1.23%, respectively, P = 0.3553). CONCLUSION: Stone fragmentation may be induced by PS friction effect. Also, screw-shaped plastic stents may improve friction effect. These results may help guide future PS development and clinical decisions.

Vascular enhancement pattern of mass in computed tomography may predict chemo-responsiveness in advanced pancreatic cancer.

INTRODUCTION: Chemo-responsiveness in pancreatic cancer is known to be dependent on fibrosis and vascularity. The purpose of this study was to assess vascular enhancement in advanced pancreatic adenocarcinoma with or without liver metastasis in computed tomography (CT) and to analyze the correlation between enhancement patterns and chemo-responsiveness. METHODS: Patients were assigned to either a responder group (partial response or stable disease) or a non-responder group (progressive disease) according to chemo-responsiveness assessed by CT before and after gemcitabine-based chemotherapy. Hounsefield unit (HU) was measured in pancreatic mass and the largest metastatic liver mass using region of interest (ROI). HU differences (ΔHU) between arterial and pre-contrast phase were calculated. RESULTS: Of the 101 study subjects, 78(77.2%) were assigned to the pancreas responder group {mean ΔHU (±SD), 36.7(±21.6)} and 23(22.8%) to the pancreas non-responder group {mean ΔHU (±SD), 20.6(±9.9)} (p = 0.001 for ΔHUs). Of the 46 study subjects with liver metastasis, 25(54.3%) were assigned to the liver metastasis responder group {mean ΔHU (±SD), 36.9(±21.0} and 21(45.7%) to the liver metastasis non-responder group {mean ΔHU (±SD), 17.1 (±24.0)}, (p = 0.005 for ΔHUs). CONCLUSION: CT determined mass vascular enhancement patterns may predict chemoresponse in advanced pancreatic cancer.

Clinical response to dorsal duct drainage via the minor papilla in refractory obstructing chronic calcific pancreatitis.

Background and study aims Complete stone removal from the main pancreatic duct might not be achieved in all patients with obstructive chronic calcific pancreatitis. We report our results for endoscopic dorsal pancreatic duct (DPD) bypass of obstructing stones in the ventral pancreatic duct (VPD). Patients and methods 16 patients with obstructive chronic calcific pancreatitis were treated with a DPD bypass. Clinical success was defined as significant pain relief and no hospital admissions for pain management during the ongoing treatment period. Results Among 16 patients meeting entry criteria, 10 (62.5 %) had a history of unsuccessful endoscopic therapy, and 8 had failed extracorporeal shockwave lithotripsy (ESWL). Clinical success was achieved in 12 patients (75 %). Among these responders, 10 patients (83.3 %) had markedly improved or complete pain relief after the first stent placement, which persisted throughout the follow-up period; 11 patients (91.7 %) were able to discontinue their daily analgesics. Conclusions In selected patients with obstructive chronic calcific pancreatitis, the DPD bypass may be considered as a rescue endoscopic therapy, potentially obviating the need for surgery when standard endoscopic methods and ESWL fail.

The Stent Patency and Migration Rate of Different Shaped Plastic Stents in Bile Flow Phantom Model and In Vivo Animal Bile Duct Dilation Model.

BACKGROUND/AIM: In research and development of biliary plastic stents (PS), continuous efforts have been made to overcome short patency time and high rate of migration. The aim of this study was to evaluate the patency and migration rate of different PS shapes for a given period of time. METHODS: Using an in vitro bile phantom model, we compared the patency among different shapes of PS (three straight PS, four double-pigtail PS, and a new screw-shaped PS). We performed an analysis of the degree of luminal narrowing by light microscopic examination. Using an in vivo swine model, we compared the patency and migration rate among the three different types of PS. RESULTS: Eight weeks after the bile exposure in the bile flow phantom model, 80 PS were retrieved and analyzed. The straight PS showed less biofilm formation and luminal narrowing than other types of PS (p < 0.05). Forty-nine PS were inserted into the dilated bile ducts of 10 swine models, and 39 PS were successfully retrieved 8 weeks later. The stent migration occurred less frequently in the double-pigtail PS and the screw-shaped PS than it did in the straight PS (11.1, 10, and 27.3%, respectively). However, there was no statistical difference in stent patency among the different shapes. CONCLUSIONS: Stent patency may not be significantly different depending on the shape of PS for 8 weeks. The screw-shaped PS showed similar patency and migration rate to the double-pigtail PS. These results may help guiding future PS development and clinical decisions.

Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice.

AIM: Effective therapy to treat acute pancreatitis (AP) or to prevent its recurrence/complication is still not available. Based on previous results that suggest that: i) hydrogen sulfide (H2S) levels were significantly increased in pancreatitis and gastritis and ii) Korean red ginseng (KRG) efficiently attenuated Helicobacter pylori-associated gastritis through the suppressive actions of H2S, we hypothesized that KRG can ameliorate experimental pancreatitis through suppression of H2S generation. METHODS: C57BL/6 mice were pre-administered KRG and then subjected to cerulein injection or pancreatic duct ligation (PDL) to induce pancreatitis. Blood and pancreas tissues were collected and processed to measure serum levels of amylase, lipase and myeloperoxidase and the concentration of H2S and the levels of various inflammatory cytokine in pancreatic tissues of mice with induced AP. RESULTS: KRG significantly inhibited NaHS-induced COX-2 and TNF-α mRNA in pancreatic cells, but dl-propargylglycine did not. KRG ameliorated cerulein-induced edematous pancreatitis accompanied with significant inactivation of NF-κB and JNK in pancreatic tissues of C57BL/6 mice (p < 0.001) and also significantly ameliorated PDL-induced necrotizing pancreatitis (p<0.01); in both conditions, the significant suppression of H2S resulting from KRG pretreatment afforded rescuing outcomes. Along with suppressed levels of H2S consequent to depressed expressions of CBS and CSE mRNA, KRG administration efficiently decreased the serum level of amylase, lipase, and myeloperoxidase and the expression of inflammatory cytokines in animal models of mild or severe AP. CONCLUSIONS: These results provide evidence for the preventive and therapeutic roles of KRG against AP mediated by H2S suppression.