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Rodent models, which have played important roles in preclinical research of pancreas and biliary diseases, have some limitations to translating data from rodent models to human diseases. Large animal models have recently been developed to overcome these limitations and perform translational research of medical devices and drugs in pancreas and biliary diseases. Preclinical studies using large animal models are necessary before clinical application, especially for the research and development of equipment, instrumentation, and techniques in pancreato-biliary diseases. As long as the endoscope used in humans can enter an organ, there appears to be no limitation in terms of species or organ for endoscopic experiments of large animal models. Investigators have mainly used swine for pancreas and biliary endoscopic experiments. Until now, unique swine models that investigators have been established include the normal bile duct model, bile duct dilation model, bile duct dilation+direct peroral cholangioscopy model, benign biliary stricture model, hilar biliary obstruction model, and acute pancreatitis (post-ERCP pancreatitis) model. Many preclinical studies have been performed using these established endoscopy-based large animal models to develop novel medical devices. Furthermore, porcine pancreatic cancer models induced by a transgenic or orthotopic method are currently under development. These models appear to be available for general use in the future and will have multiple potential preclinical and clinical applications.

Side-by-side (SBS) bilateral placement of self-expandable metal stents (SEMSs) is limited by technical difficulties in cases of malignant hilar bile duct obstruction (MHBO). Recently, a braided SEM...

Backgrounds and aim Multiple insertions of self-expandable metal stents (SEMS) for advanced malignant hilar obstruction (MHO) are now considered to be an effective palliative method for adequate drainage of liver volume. However, the efficacy of endoscopic reintervention in technically and clinically successful bilateral SEMS is limited. This study investigated the endoscopic revision efficacy in patients who underwent bilateral SEMS in MHO. Methods Primary endoscopic revision using plastic or metal stents or an alternative percutaneous approach followed by secondary endoscopic revision was performed in patients who underwent clinically successful deployment of bilateral SEMS. The primary outcome was a technical success. Secondary outcomes were clinical success, adverse events, and patency duration after reintervention. Results A total of 55 patients (83.3%) out of 66 enrolled patients underwent reintervention: primary endoscopic reintervention (n = 47) and secondary endoscopic revision following percutaneous drainage (n = 8). Intended technical success rates of primary and secondary endoscopic reintervention were 93.6% (44/47) and 87.5% (7/8), respectively (P = 0.47). Clinical success rates were 72.3% and 50%, respectively (P = 0.23). Stent malfunction rate after reintervention was 48.9% (23/47) and 37.5% (3/8) (P = 0.70) during follow up, and median cumulative stent patency duration was 119 and 55 days, respectively (log-rank P = 0.68). Stent patent rate after reintervention was not different according to the time interval. In univariate and multivariate analysis for stent patency duration-related factors after reintervention, there were no meaningful factors. Conclusion Primary endoscopic reintervention for bilateral SEMS in MHO was feasible technically and clinically. However, there were no statistically meaningful factors for stent patency duration after reintervention.

Endoscopic management of benign biliary stricture (BBS) remains challenging. Stenting is currently used for BBS management, but refractory BBS remains problematic. The aim of this study was to assess the safety and feasibility of a dilation balloon-equipped cylindrical light diffuser for BBS in a large animal model. A total of seven mini-pigs were used in the current study. Laser settings were chosen based on the findings of a previous animal study. Five animals were used in a preliminary study to establish process conditions. BBSs were created in the common bile ducts of the other two animals by intraductal radiofrequency ablation (RFA) via endoscopic retrograde cholangiography (ERC). At 4 weeks post-RFA, laser ablation was performed using a customized balloon-equipped cylindrical diffuser at 10 W for 10 s while maintaining balloon inflation for 10 s at 5 atm. A follow-up ERC was performed at 4 weeks post-laser ablation and the animals were sacrificed for histologic evaluation. BBS was observed in all animals by ERC at 4 weeks post-RFA. The mean bile duct stricture diameter in the two animals as determined by ERC was 0.8 mm. Laser ablations were performed without technical difficulty and no adverse event was encountered. At 4 weeks post-laser ablation, mean biliary stricture diameter had dilated to 1.6 mm on cholangiographic finding. On histologic examination, inflammatory cell infiltration in lamina propria and dense collagen deposition were observed, but there was no evidence of bile duct perforation. The devised balloon-equipped cylindrical laser light diffuser appears to be safe and feasible for the treatment of BBS. However, further studies and modifications are required before it can be applied clinically as a monotherapy.

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.

Background : The submucosal lifting gel (Cook Medical Inc., Winston-Salem, NC, USA) is a novel injectate for submucosal lifting of gastrointestinal lesions. The aim of this study was to evaluate the efficacy of the novel submucosal lifting gel for performing endoscopic mucosal resection after precutting (EMR-P) in large gastric lesions. Methods : A total of 31 artificial lesions were created on body of stomach by electrocautery marking with endoscopic ruler in five live micro-pigs. Three different groups were randomly assigned by the size of artificial lesion such as 3 cm (group 1, 11 cases), 3.5 cm (group 2, 10 cases), and 4 cm (group 3, 10 cases) in diameter. Then EMR-P was performed after injection the lifting gel sufficient unto submucosal layer. Independent observer recorded circumferential resection time, submucosal injection time, injection amount, total procedure time, en bloc and perforation rate. Results : The mean circumferential resection time was significantly longer in the group 3 in comparison with group 1 and 2 (6.7 ± 1.7 min vs 4.2 ± 1.4 min, P < 0.001 and 4.7 ± 1.5 min, P = 0.004). The mean total procedure time and amount of injection were significant difference between three groups (9.6 ± 2.2 min vs 12.9 ± 2.6 min vs 17.4 ± 2.2 min, P < 0.01) (5.2 ± 1.1 mL vs 6.9 ± 1.4 mL vs 9.3 ± 3.0 mL, P = 0.02). The en bloc rate of each group was 90.9% (10/11), 60.0% (6/10), and 50.0% (5/10) in the group 1, 2, and 3 respectively. There was a perforation during circumferential cutting in group 2. Conclusion : In a porcine model, a new submucosal lifting gel seems to improve the en bloc rate for performing EMR-P in large gastric lesions, especially 3 cm in diameter.

Background/aims A reproducible, endoscope-based, large animal model, of acute pancreatitis was developed to meet the need for a suitable means of preclinically testing treatments. The aim of this study was to develop an endoscope-based animal model of acute pancreatitis. Methods This experimental study was conducted on six mini-pigs. The pancreatitis model was induced by infusing contrast medium (CM) or sodium taurocholate (TCA) under high pressure (100 mmHg) into the main pancreatic duct by endoscopic retrograde pancreatography. Animals were randomly allocated to three groups: a CM group, a 10% TCA group, and a 20% TCA group. Pancreatic injuries were evaluated histologically, and serum amylase and lipase levels were measured. Results Acute pancreatitis was observed in all animals during hematologic and histologic examinations. Serum amylase and lipase levels were significantly higher (> 10 times baseline), and pancreatic edema, vacuolization of acinar cells, and hemorrhagic necrosis were observed. Severity of pancreatitis tended to be greater in the TCA groups than in the CM group as assessed using histologic scores, and degrees of pancreatitis were found to be dose-dependently related to TCA concentration. Conclusion The two endoscopic procedures described are effective and safe for creating a swine model of acute pancreatitis. The authors hope the described endoscopic methods will assist in the development of a suitable treatment strategy.

Background/Aims Metallic stents designed to relieve malignant biliary obstruction are susceptible to occlusive tumor ingrowth or overgrowth. In a previous report, we described metallic stents covered with paclitaxel-incorporated membrane (MSCPM-I, II) to prevent occlusion from tumor ingrowth via antitumor effect. This new generation paclitaxel-eluting biliary stent is further endowed with sodium caprate (MSCPM-III) for enhanced drug delivery. The purpose of this study is to examine the safety of its drug delivery system in the porcine biliary tract. Methods MSCPM-III (10% [wt/vol] paclitaxel) and covered metal stents (CMSs) were endoscopically inserted in porcine bile ducts in vivo. Histologic biliary changes, levels of paclitaxel released, and various serum analytes (albumin, alkaline phosphate, aspartate transaminase, alanine transaminase, total protein, total bilirubin, and direct bilirubin) were assessed. Results Based on the intensity of reactive inflammation and fibrosis, changes in porcine biliary epithelium secondary to implanted MSCPM-III were deemed acceptable (i.e., safe). Histologic features in the MSCPM-III and CMS groups did not differ significantly. In a related serum analysis, paclitaxel release from MSCPM-III stents was below the limit of detection for 28 days. Biochemical analyses were also similar for the two groups, and no evidence of hepatic or renal toxicity was found in animals receiving MSCPM-III stents. Conclusions In a prototypic porcine trial, this newly devised metal biliary stent incorporating both paclitaxel and sodium caprate appears to be safe in the porcine bile duct.

Background and study aims Use of fully covered self-expandable metal stents (FCSEMS) for biliary drainage of malignant hilar biliary strictures is limited because of risk of cholangitis due to side branch obstruction. The aim of this study was to evaluate the safety and efficacy of unilateral placement of a multi-hole FCSEMS (FCSEMS-MH), which had a 2.5-mm hole in the center of the membrane on each cavity, in a swine model of hilar biliary stricture. Materials and methods Six female mini pigs were included in this prospective study. The hilar biliary stricture model was prepared using an endobiliary radiofrequency ablation. FCSEMS-MHs were endoscopically inserted into the peri-hilar bile duct of all the animals. Outcomes were assessed in terms of adverse events (AEs) including cholangitis, stent patency, stent migration, and endoscopic stent removability for 1 month after stenting. Results In terms of hilar biliary stricture types, two animals were of Bismuth type I and four were of type II. Technical success rate for endoscopic metal stenting was 100 % (6/6), and the functional success rate, which was evaluated 7 days after stent insertion, was also 100 % (5/5). The immediate overall AE rate was 0 %. There was no procedure-related mortality and stent migration did not occur in any animal during the 4-week stent indwelling period. Stents were removed from all six animals at 4 weeks post-stenting. Conclusion Unilateral placement of FCSEMS-MH might be safe and effect for swine hilar biliary stricture models. However, long-term follow-up and comparative studies are needed to verify the usefulness of this stent.

Background and Aim: Post endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis is not an uncommon adverse event but may not be avoidable. Various pharmacological and endoscopic te...

Background A new hemostatic adhesive powder (UI-EWD) has been developed to reduce the high re-bleeding rates associated with the currently available hemostatic powders. The current study aimed to assess the efficacy of UI-EWD as a salvage therapy for the treatment of refractory upper gastrointestinal bleeding (UGIB). Methods A total of 17 consecutive patients who had failed to achieve hemostasis with conventional endoscopic procedures and had undergone treatment with UI-EWD for endoscopic hemostasis in refractory UGIB were prospectively enrolled in the study. We evaluated the success rate of initial hemostasis and rate of re-bleeding within 30 days. Results All patients underwent successful UI-EWD application at the bleeding site. Initial hemostasis occurred in 16/17 patients (94 %). Re-bleeding within 30 days occurred in 3/16 patients (19 %) who had achieved initial hemostasis. In the second-look endoscopy after 24 hours, hydrogel from UI-EWD was found attached at the bleeding site in 11/16 patients (69 %). Conclusion UI-EWD has a high success rate for initial hemostasis in refractory UGIB and shows promising results in the prevention of re-bleeding.

Hypoxemia can occur during endoscopic retrograde cholangiography (ERCP) and it is difficult to achieve adequate ventilation with the prone position. High-flow nasal oxygen (HFNO) has been recommended to be more effectively help ventilation than conventional low flow oxygen. The aim of this study was to evaluate the effect of HFNO during sedated ERCP and to identify predictors of desaturation during ERCP. The investigated variables were age, gender, American Society of Anesthesiologists classes (ASA), duration of exam, and sedative used for midazolam or/and propofol of 262 patients with sedated ERCP. The differences between categorical and continuous variables were analyzed using the Student’s t test and the chi-square test. Desaturation (SpO2 ≤ 90%) occurred in 9(3.4%) patients among 262 patients during sedated ERCP. The variables found to predict desaturation were older age (p p p

Background and Aim. Needle-knife sphincterotomy (NKS) is currently recommended as the second option in cases of difficult cannulation due to its potential higher adverse event rate. However, the clinical outcomes of NKS have not been evaluated as thoroughly as those of the primary cannulation technique. The aim of the current study was to investigate the feasibility, efficacy, and safety of NKS when used for primary access in patients at high risk of developing postendoscopic retrograde cholangiopancreatography pancreatitis (PEP). Methods. Forty patients with one or more risk factors for PEP were prospectively enrolled between June 2018 and November 2019. The cannulation was conducted in all patients using NKS as the primary cannulation technique. Success rate of biliary cannulation, biliary cannulation time, and adverse event rate were assessed. Results. Of the 40 patients enrolled, 34 patients underwent primary NKS after the screening. Nine patients had 1 risk factor for PEP, 7 had 2, 8 had 3, 7 had 4, and 3 had 5. The success rate of biliary access by NKS was 94.1% (32/34). The median procedure time for NKS and the total procedure time for stone removal or biliary drainage were 4.1 minutes (range, 0.5-25.2) and 11.3 minutes (range, 3.8–40.4), respectively. Adverse events occurred in two patients (minor bleeding, n = 1 ; hyperamylasemia, n = 1 ). No patient experienced PEP or perforation. Conclusion. NKS might be feasible as a primary cannulation procedure in patients at high risk of PEP. This trial is registered with KCT0004886 (03/06/2018).

Background The use of a lumen-apposing metal stent (LAMS) capable of one-step endoscopic ultrasound-guided transmural drainage (EUS-TD) can increase the effectiveness of the procedure. We evaluated the newly developed electrocautery-enhanced (EC) delivery system with a LAMS for one-step EUS-guided gallbladder drainage (EUS-GBD) or choledochoduodenostomy (EUS-CDS). Methods In the animal experiment, an EC-LAMS was advanced into the gallbladder without prior tract dilation in four pigs. A conventional LAMS was inserted in another four pigs as a control group. After the animal experiment, 17 patients underwent EUS-TD using the EC-LAMS (EUS-GBD in 10 patients, EUS-CDS in 7). The primary outcome was the technical success rate. Results In the animal study, the mean procedure time was significantly shorter in the EC-LAMS group than in the conventional LAMS group. In the human study, the overall technical success rate was 94.1 %, with one EUS-GBD failure. The clinical success rate was 100 %. The overall adverse event rate was 17.6 %. Conclusions One-step EUS-GBD or EUS-CDS using the novel EC-LAMS is a feasible approach that achieves a high success rate and maintains safety.

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.

Pancreatitis is the inflammation of the pancreas. However, little is known about the genes associated with pancreatitis severity. Our microarray analysis of pancreatic tissues from mild and severe acute pancreatitis mice models identified angiopoietin‐like 4 (ANGPTL4) as one of the most significantly upregulated genes. Clinically, ANGPTL4 expression was also increased in the serum and pancreatic tissues of pancreatitis patients. The deficiency in ANGPTL4 in mice, either by gene deletion or neutralizing antibody, mitigated pancreatitis‐associated pathological outcomes. Conversely, exogenous ANGPTL4 exacerbated pancreatic injury with elevated cytokine levels and apoptotic cell death. High ANGPTL4 enhanced macrophage activation and infiltration into the pancreas, which increased complement component 5a (C5a) level through PI3K/AKT signaling. The activation of the C5a receptor led to hypercytokinemia that accelerated acinar cell damage and furthered pancreatitis. Indeed, C5a neutralizing antibody decreased inflammatory response in LPS‐activated macrophages and alleviated pancreatitis severity. In agreement, there was a significant positive correlation between C5a and ANGPTL4 levels in pancreatitis patients. Taken together, our study suggests that targeting ANGPTL4 is a potential strategy for the treatment of pancreatitis., This study identifies ANGPTL4 as a potential pathological mediator that induces pancreatitis. Targeting ANGPTL4 by a neutralizing antibody is shown to be an effective strategy for the treatment of pancreatitis in mice.

Background/aims Endoscopic retrograde cholangiopancreatography (ERCP) is used as a curative method for choledocholithiasis, but little is known about ERCP for patients with end-stage renal disease (ESRD) on hemodialysis (HD). The aim of the current study was to evaluate the efficacy and safety of ERCP for patients with ESRD on HD and to identify the risk factors of ERCP-related bleeding. Materials and methods The medical records of 61 ESRD patients with choledocholithiasis who underwent ERCP were retrospectively investigated with respect to successful bile duct stone removal and procedure-related adverse events such as pancreatitis, bleeding, and cholangitis. Results For the study subjects, the overall stone removal success rate was 96.7%, and the overall ERCP-related adverse event rate was 21.3% (pancreatitis, 4.9%; bleeding, 13.1%; cholangitis, 6.6%). Endoscopic sphincterotomy (EST) was found to be associated with hemorrhage (p=0.02), and the occurrence of hemorrhage in patients who underwent EST with or without endoscopic papillary balloon dilation (EPBD) was significantly higher than that in patients who underwent EPBD alone (Odds ratio 1.27, 95% confidence interval 1.075-1.493, p=0.02). Conclusion ERCP for ESRD patients was found to be feasible and safe. However, EST was significantly related to hemorrhagic events. EPBD reduced the risk of hemorrhage and was as effective as EST in terms of stone removal.

Endoscopic ultrasonography (EUS)-guided transmural drainage has been accepted as a modality of choice in peripancreatic fluid collection and acute cholecystitis. Each type of stent, including double-pigtail plastic stents, tubular self-expandable metal stents (SEMS), and lumen-apposing metal stents, for these procedure has its own advantages and disadvantages. To overcome their disadvantages, this animal study evaluated the feasibility of a newly designed twisted fully covered SEMS with spiral coiled ends. We performed the EUS-guided cholecystogastrostomy with a newly developed metal stent in eight mini pigs with surgically induced gallbladder distension. This novel stent is a twisted fully covered SEMS with spiral coiled ends, a diameter of 8 mm, and a length of 6 cm. The stent has been maintained for four to seven weeks after EUS-guided cholecystogastrostomy. The primary outcome was the technical success rate, and the secondary outcomes were adverse events, stent dysfunction, stent removability, and fistula formation. The stent was placed successfully between the gallbladder and the stomach in all cases without any adverse event. We observed neither stent migration nor dysfunction during the study period, and all the stents were removed easily as scheduled. We confirmed successful cholecysto-gastric fistula formation at endoscopic and histologic level in all cases. EUS-guided transmural drainage and fistula formation using a new twisted fully covered metal stent with spiral coiled ends was technically feasible without any adverse event in this animal study. Further clinical studies are needed to evaluate its efficacy and safety in real practice.

Acute acalculous cholecystitis (AAC) traditionally occurs in critically ill patients with chronic debilitating diseases, those with superimposed critical illness, trauma, or major burns. Ultrasonography (US), computed tomography (CT), and a hepatobiliary iminodiacetic acid (HIDA) scan are diagnostic imaging modalities used in patients with a high index of clinical suspicion during the early stage of AAC. Diagnostic criteria for AAC using US/CT include gallbladder (GB) wall thickness ≥3.5 mm, pericholecystic fluid or subserosal edema, intramural gas, coarse mucosa, sludge, and hydrops. The most common indication for a HIDA scan is acute cholecystitis diagnosed by nonvisualization of the GB secondary to cystic duct obstruction. Cholecystectomy is the mainstay of treatment for AAC, particularly in patients with suspected perforation or gangrene. Several studies report that percutaneous cholecystostomy not only serves as a bridge for cholecystectomy but can also definitively treat AAC, particularly in high-risk surgical patients. Endoscopically placed lumen-apposing metal stents are useful for safe and effective transmural GB drainage in patients with AAC. Early diagnosis and prompt treatment are essential to avoid a fulminant course and complications, such as gangrene or perforation associated with high mortality rates.

Background/Aims Although endoscopic bilateral stent-in-stent placement is challenging, many recent studies have reported promising outcomes regarding technical success and endoscopic re-intervention. This study aimed to evaluate the technical accessibility of stent-in-stent placement using large cell-type stents in patients with inoperable malignant hilar biliary obstruction. Methods Forty-three patients with inoperable malignant hilar biliary obstruction from four academic centers were prospectively enrolled from March 2013 to June 2015. Results Bilateral stent-in-stent placement using two large cell-type stents was successfully performed in 88.4% of the patients (38/43). In four of the five cases with technical failure, the delivery sheath of the second stent became caught in the hook-cross-type vertex of the large cell of the first stent, and subsequent attempts to pass a guidewire and stent assembly through the mesh failed. Functional success was achieved in all cases of technical success. Stent occlusion occurred in 63.2% of the patients (24/38), with a median patient survival of 300 days. The median stent patency was 198 days. The stent patency rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months postoperatively, respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10 underwent percutaneous drainage. Conclusions Large cell-type stents for endoscopic bilateral stent-in-stent placement had acceptable functional success and stent patency when technically successful. However, the technical difficulty associated with the entanglement of the second stent delivery sheath in the hook-cross-type vertex of the first stent may preclude large cell-type stents from being considered as a dedicated standard tool for stent-in-stent placement.

Backgrounds The placement of a self-expandable metal stent (SEMS) is widely used in patients with unresectable malignant biliary obstructions, but SEMSs are susceptible to occlusion by tumor ingrowth or overgrowth. The efficacy and safety of a novel paclitaxel-eluting biliary metal stent incorporating sodium caprate (MSCPM-III) were compared prospectively with those of a covered metal stent (CMS) in patients with malignant biliary obstructions. Methods Patients with unresectable distal malignant biliary obstructions (n = 106) were prospectively enrolled in this study at multiple treatment centers. Stents were placed endoscopically: MSCPM-III in 54 patients and CMS in 51 patients. The patients received systemic chemotherapy regimens according to their disease characteristics. Results The two groups did not differ significantly in basic characteristics or mean follow-up period. Stent occlusion occurred in 14 patients who received MSCPM-III and in 11 patients who received CMS. Time to recurrent biliary obstruction (RBO) and survival time did not differ significantly between the two groups (P = 0.84 and P = 0.29, respectively). However, tumor size at 2 months after stent insertion was significantly decreased in patients in the MSCPM-III group with bile duct cancers or those who experienced stent migration compared with the CMS group. Complications, including cholangitis and pancreatitis, were found to be acceptable in both groups. Conclusions Although compared with a CMS the MSCPM-III did not significantly influence time to RBO or survival duration in patients with malignant biliary obstructions, MSCPM-III reduced tumor volume and was used safely in humans.

Endoscopically applicable hemostatic agents have been demonstrated to have high initial hemostasis rates in cases of upper gastrointestinal bleeding (UGIB). The authors developed a new hemostatic powder (CEGP-003) and evaluated its hemostatic and ulcer healing effects in UGIB. Patients with peptic ulcer or post-endoscopic resection bleeding were randomly assigned to be treated by epinephrine injection or CEGP-003 spray. All patients were placed under observation for 3 days and underwent second-look endoscopy. The primary outcome was initial hemostasis rate, and the secondary outcomes were rebleeding rate and ulcer healing effect. Seventy-two patients with UGIB were enrolled in this study. Causes of bleeding were peptic ulcer (15, 20.5%), post-endoscopic mucosal resection (11, 15.1%), and post-endoscopic submucosal dissection bleeding (47, 64.4%). Initial hemostasis was achieved in 89.2% (34/37) of patients in the epinephrine group and in 100% (35/35) in the CEGP-003 group (p = 0.115). Rebleeding occurred in 2.7% (1/37) and 8.6% (3/35) in the epinephrine and CEGP-003 groups, respectively (p = 0.35). Three days after endoscopic hemostasis, the ulcer healing effects of epinephrine and CEGP-003 were similar (p = 0.79). This study shows that CEGP-003 spray has a hemostatic effect similar to epinephrine in terms of initial hemostasis and rebleeding rates. The authors consider CEGP-003 a potential therapeutic tool for UGIB as a definitive or bridge therapy and that it is particularly useful for oozing lesions after endoscopic resection.

AIM We aimed to identify the incidence rate of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with entecavir or tenofovir in South Korea, and to identify predictors of HCC development in these patients. METHODS Between January 2007 and December 2015, 582 CHB patients initially received entecavir (n = 406, 69.8%) or tenofovir (n = 176, 30.2%) for CHB. RESULTS During a median follow-up of 57.1 months, HCC developed in 38 (6.5%) of the 582 patients, regardless of antiviral agent type. Entecavir- and tenofovir-treated patients had similar HCC development rates (P = 0.471). For the 582 patients, 2-, 4-, and 6-year cumulative HCC development rates were 2.6%, 4.4%, and 8.3%, respectively, and the 2-, 4-, and 6-year cumulative HCC development rates of patients with liver cirrhosis were significantly greater than those of patients without liver cirrhosis (6.2%, 9.8%, and 18.4% vs. 0.3%, 1.1%, and 2.2%, respectively; P

Background and Aims Endobiliary radiofrequency ablation (EB-RFA) is a new adjunctive method for biliary drainage restoration. However, a concern remains about long-term adverse events of this procedure, such as biliary stricture, perforation, and hemorrhage. Therefore, we aimed to assess the long-term effects of in vivo EB-RFA in a swine model. Methods Six mini-pigs were divided into 2 groups: 10-W/33-mm EB-RFA and 7-W/18-mm EB-RFA. Endoscopic retrograde cholangiography–guided temperature controlled EB-RFA (80°C, 7-10 W, 120 seconds) was performed. After 28 days all mini-pigs underwent follow-up ERC and were killed to assess the long-term effects of EB-RFA. Results All mini-pigs developed biliary stricture (median length, 10.5 mm; range, 6-15) with jaundice (total bilirubin, 5.84 mg/dL; range, 4.3-9.2) and purulent bile at 1 month after EB-RFA. A significant difference was found in the length of stricture on cholangiogram between the 10 W/33-mm and 7 W/18-mm EB-RFA groups (median, 14 vs 6 mm; P = .034); however, no differences were found in the width of the stricture and laboratory findings. Histologic examination revealed marked thickening of bile duct with severe damage of whole layers replaced with reactive myofibroblastic proliferation, dense collagen laydown, chronic and acute inflammation, and fat necrosis. However, long-term adverse events, such as perforation or hemorrhage, were not found. Conclusions As a long-term result of EB-RFA, segmental biliary stricture with cholangitis develops in proportion to the power/length of the RFA electrode. Therefore, biliary stents should be placed to maintain biliary drainage after EB-RFA.

Objectives In patients with irretrievable or intractable bile duct stone, temporary insertion of plastic stent (PS) followed by further ERCP or surgery has been recommended as a “bridge” therapy. However, the exact mechanism of stone fragmentation has not been discovered. The aim of this 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 the three different PS groups (straight PS group; double pigtail-shaped PS group, and screw-shaped PS group) and the control group. Each group had 10 silicon tube rooms that separately contained one stone and two PS. The control group had 10 rooms each with only a stone and no PS. We performed an analysis of the friction effect by the stone weight and volume changes among the groups, excluding fragmented stones. Results After eight weeks, complete fragmentation was noted in one out of 34 cholesterol stones (2.9%), and four out of six pigmented stones (66.7%). They tended to be more prominent in the screw-shaped PS group than them they were 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, the screw-shaped plastic stents may improve friction effect. These results may help guide future PS development and clinical decisions. This article is protected by copyright. All rights reserved.

Background/Aims A drug-eluting stent for unresectable malignant biliary obstruction was developed to increase stent patency by preventing tumor ingrowth. The safety and efficacy of a new generation of metallic stents covered with a paclitaxel-incorporated membrane using a Pluronic® mixture (MSCPM-II) were compared prospectively with those of covered metal stents (CMSs) in patients with malignant biliary obstructions. Methods This study was initially designed as a prospective randomized trial but was closed early because of a high incidence of early occlusion. Therefore, the data were analyzed using the intent-to-treat method. A total of 72 patients with unresectable distal malignant biliary obstructions were prospectively enrolled. Results The two groups did not differ significantly in basic characteristics and mean follow-up period (MSCPM-II 194 days vs CMS 277 days, p=0.063). Stent occlusion occurred in 14 patients (35%) who received MSCPM-II and in seven patients (21.9%) who received CMSs. Stent patency and survival time did not significantly differ between the two groups (p=0.355 and p=0.570). The complications were mild and resolved by conservative management in both groups. Conclusions There were no significant differences in stent patency or patient survival in MSCPM-II and CMS patients with malignant biliary obstructions.

BACKGROUND AND AIM Endobiliary radiofrequency ablation (EB-RFA) is a new endoscopic palliation and adjunctive tool. Although EB-RFA is performed worldwide, a possibility of iatrogenic thermal injury leading to perforation or bleeding still remains. Therefore, we aimed to assess the effects of thermal and coagulation injury after in vivo EB-RFA using a new catheter with a temperature sensor in a swine model. METHODS Twelve mini pigs were divided into four groups according to power (33 mm 10 W electrode vs. 18 mm 7 W electrode) and RFA target temperature (75°C vs. 80°C). All mini pigs underwent endoscopic retrograde cholangiography and target temperature controlled EB-RFA for 120 s. Additional cholangiogram was taken immediately after RFA, and all pigs were sacrificed after 24 h to assess the macroscopic/microscopic RFA injury. RESULTS Microscopic maximal injury depth and ablation area of EB-RFA using a 33-mm 10 W RFA electrode were significantly deeper and larger than those of EB-RFA using an 18-mm 7 W electrode (median; 2.7 vs. 2.1 mm, P = 0.004, 48.9 vs. 36.2 mm2 , P = 0.016). However, there were no significant differences in microscopic ablation parameters between two different RFA target temperatures (75°C vs. 80°C). In addition, a post-RFA cholangiogram and assessment of the resected specimen at 24 h after the RFA showed no adverse events such as perforation or bleeding. CONCLUSIONS EB-RFA using a temperature controlled RFA catheter successfully ablates the bile duct wall without adverse events in a swine model.

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.

Biliary drainage in malignant biliary obstruction improves patient survival and quality of life (Huibregtse et al., Endoscopy 21:280–282, 1989). Endoscopic stenting is increasingly being used in the management of biliary obstruction and has become the current treatment of choice for the palliation of blockage caused by malignant (Neuhaus et al., Endoscopy 21:225–228, 1989; Irving et al., Radiology 172:321–326, 1989; Dumonceau et al., Endoscopy 44:277–298, 2012). A variety of stents have been developed to enhance the efficacy of the procedure, and improvements are ongoing. In this article, we review the recent advances in biliary stent. We describe the rationale behind the design and the resulting outcome for each stent type.

Background and study aims A new hemostatic adhesive powder (UI-EWD) was developed to reduce high rebleeding rates and technical challenges associated with application of currently available hemostatic powders. The aim of the current study was to assess performance of UI-EWD for nonvariceal upper gastrointestinal bleeding (NVUGIB). Patients and methods A total of 56 consecutive patients that received UI-EWD monotherapy for endoscopic hemostasis due to NVUGIB were retrospectively reviewed. Main study outcomes were success rates with immediate hemostasis and rebleeding within 30 days. Outcomes were analyzed by reviewing patient medical records. Results Etiologies of bleeding were: post-endoscopic therapy bleeding in 46 (82.1 %), peptic ulcer in 8 (14.3 %), tumor in 1 (1.8 %), and other in 1 (1.8 %). UI-EWD was successfully applied at bleeding site in all cases. The success rate of immediate hemostasis was 96.4 % (54/56), and the 30-day rebleeding rate among patients that achieved immediate hemostasis was 3.7 % (2/54). No adverse event related to use of UI-EWD occurred. Conclusion UI-EWD was found to have a high immediate hemostasis success rate in NVUGIB when used as monotherapy and showed promising results in terms of preventing rebleeding.

This study investigated the effectiveness of new hemostatic adhesive powder (UI-EWD) in a swine mode of acute gastric bleeding. Gastric ulcer bleeding was induced endoscopically at two locations in each of eight heparinized mini-pigs. UI-EWD and saline were sprayed endoscopically in the experimental (n = 5) and control groups (n = 3), respectively. The hemostatic effect and hydrogel persistence on ulcers were periodically evaluated endoscopically. Initial hemostasis was achieved successfully in all lesions in the experimental group. Follow-up endoscopy showed minor delayed bleeding in 10% at 6 hours in the experimental group, whereas re-bleeding was observed in 50% at 6 hours in the control group. UI-EWD gel persisted at 90%, 80%, and 50% of ulcer bases at 6, 18, and 42 hours post-application, respectively. This study suggests that muco-adhesive UI-EWD may be effective in the endoscopic treatment of active ulcer bleeding.

To prevent stent migration, transpapillary stent placement has been recommended for the endoscopic treatment of malignant hilar biliary stricture. However, recent studies have suggested that placement above the papilla achieves better results, because it is believed to prevent reflux and prolong stent patency. The aim of this study was to compare the efficacy and safety aspects of transpapillary and suprapapillary stent placement. In addition, the success rates of stent revision were evaluated. The medical records of 73 patients with hilar cholangiocarcinoma who underwent endoscopic metal stent insertion between January 2005 and December 2015 were retrospectively reviewed. Patients were assigned by stent location to a suprapapillary (S group; N = 44) or a transpapillary (T group; N = 29) cohort. Clinical outcomes, stent patency, adverse events, and revision success rates were compared between the two study groups. Patency periods were similar in the two groups (S; 140 vs. T; 157 days; P = 0.732). Rates of stent obstruction in the S and T groups were 63.4% and 55.2%, respectively (P = 0.470). An adverse event occurred in 15 (20.5%) of total study subjects, with no significant intergroup difference. The endoscopic revision success rate was significantly higher in the T group (P = 0.01), and the time required for revision tended to be shorter in the T group. The effectiveness and safety of suprapapillary and transpapillary stent insertion were found to be similar, but the success rate of endoscopic revision was significantly higher for the T group. Therefore, we recommend that transpapillary stent placement be considered for patients with hilar cholangiocarcinoma and biliary obstruction.

Background and aim Although endoscopic papillary large balloon dilation (EPLBD) has been widely used to facilitate the removal of difficult common bile duct stones, however, the outcomes have not yet been investigated in terms of the diameter of the balloon used. We aimed to compare the clinical outcomes between EPLBD using smaller (12-15 mm, S-EPLBD) and larger balloons (> 15 mm, L-EPLBD). Methods Six hundred seventy-two patients who underwent EPLBD with or without endoscopic sphincterotomy for common bile duct stone removal were enrolled from May 2004 to August 2014 at four tertiary referral centers in Korea. The outcomes, including the initial success rate, the success rate without endoscopic mechanical lithotripsy, the overall success rate, and adverse events between S-EPLBD and L-EPLBD groups, were retrospectively compared. Results The initial success rate, the success rate without mechanical lithotripsy, the overall success rate, and the overall adverse events were not significantly different between the two groups. The rate of severe-to-fatal adverse events was higher in the L-EPBLD group than in the S-EPLBD group (1.6% vs 0.0%, 0.020). One case of severe bleeding and two cases of fatal perforation occurred only in the L-EPLBD group. In the multivariate analysis, the use of a > 15-mm balloon was the only significant risk factor for severe-to-fatal adverse events (>0.005, 23.8 [adjusted odds ratio], 2.6-214.4 [95% confidence interval]). Conclusions L-EPLBD is significantly related to severe-to-fatal adverse events compared with S-EPLBD for common bile duct stone removal.

Background: Successful biliary cannulation is a prerequisite and important component of endoscopic retrograde cholangiopancreatography (ERCP), but conventional cannulation methods (CCMs) have a post-ERCP pancreatitis (PEP) rate of 14.1% in patients at high risk for PEP. The aims of this study were 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 two 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. Findings: 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 eight patients in the CCM group and in no patients in the NKF group (9.2% vs. 0%, p < 0.001). The rates of other complications did not differ between the groups. The biliary cannulation success rate was higher in the NKF group than in the CCM group (97.9% vs. 89.7%, p = 0.005). The mean cannulation time and total procedure time were longer in the NKF group than in the CCM group. Interpretation: NKF is an effective and safe procedure to gain primary biliary access in patients at high risk for developing PEP. Trial registration number: ClinicalTrials.gov, NCT02916199. Funding Statement: The authors state: "None." Declaration of Interests: The authors state: "None." Ethics Approval Statement: The study was approved by the institutional review boards of each institution (Approval number: 3-2017-0092).

Background/aims The covered self-expandable metal stent (CMS) was developed to prevent tumor ingrowth-induced stent occlusion during the treatment of malignant biliary obstruction. However, complications such as cholecystitis, pancreatitis, and stent migration can occur after the endoscopic insertion of CMSs. The aim of the present study was to assess the efficacy and safety of a double-layered CMS (DCMS) for the management of malignant bile duct obstruction. Methods DCMSs were endoscopically introduced into 59 patients with unresectable malignant extrahepatic biliary obstruction at four tertiary referral centers, and the patient medical records were retrospectively reviewed. Results Both the technical and functional success rates were 100%. Procedure-related complications including pancreatitis, cholangitis, stent migration, and liver abscess occurred in five patients (8.5%). The median follow-up period was 265 days (range, 31 to 752 days). Cumulative stent patency rates were 68.2% and 40.8% at 6 and 12 months, respectively. At the final follow-up, the rate of stent occlusion was 33.9% (20/59), and the median stent patency period was 276 days (range, 2 to 706 days). Conclusions The clinical outcomes of DCMSs were comparable to the outcomes previously reported for CMSs with respect to stent patency period and complication rates.

The aim of this study was to assess the feasibility of needle-knife fistulotomy (NKF) as an initial procedure for biliary access in patients with stones in the common bile duct (CBD) who were at increased risk for post-ERCP pancreatitis (PEP).Fifty-five patients who underwent ERCP with NKF for CBD stones at our institution between July 2013, and May 2015, were prospectively enrolled in this study. They had one or more of the following risk factors for PEP: young age (60 years), female sex, or normal CBD diameter (≤9 mm). The procedure was performed by an expert biliary endoscopist (S.J.). The success rate of biliary cannulation and CBD stone removal, and the incidence rate of adverse events were assessed.Seventeen patients had 1 risk factor for PEP, 27 had 2, and 11 had 3. The median procedure times for NKF and CBD stone removal after NKF were 2.1 minutes (range, 0.2-8.7 min) and 6.5 minutes (range, 1.1-28.3 min), respectively. Success rates of CBD cannulation and stone removal using NKF were 96.3% (53/55) and 92.7% (51/55), respectively. None of the patients experienced PEP. Retroperitoneal duodenal perforation occurred in 1 patient (1.8%), but it was successfully treated by conservative management.NKF might be feasible as an initial procedure for biliary access in patients with CBD stones who are at high risk for PEP if the procedure is performed by an expert biliary endoscopist. (Clinical trial registration number: KCT0001698.).

Background/Aims The efforts to improve biliary plastic stents (PSs) for decreasing biofilm formation and overcome short patency time have been continued. The aim of this study is to evaluate the effect of advanced hydrophilic coating for patency and biodurability of PS. Methods Using an in vitro bile flow phantom model, we compared patency between prototype PS with hydrophilic coating (PS+HC) and prototype PS without hydrophilic coating (PS−HC). We performed an analysis of the degree of luminal narrowing by microscopic examination. Using an in vivo swine bile duct dilation model made by endoscopic papillary closure and stent insertion, we evaluated biodurability of hydrophilic coating. Results In the phantom model, PS+HC showed less biofilm formation and luminal narrowing than PS−HC at 8 weeks (p

The large animal model with benign biliary stricture (BBS) is essential to undergo experiment on developing new devices and endoscopic treatment. This study conducted to establish a clinically relevant porcine BBS model by means of endobiliary radiofrequency ablation (RFA). Endoscopic retrograde cholangiography (ERC) was performed on 12 swine. The animals were allocated to three groups (60, 80, and 100 W) according to the electrical power level of RFA electrode. Endobiliary RFA was applied to the common bile duct for 60 seconds using an RFA catheter that was endoscopically inserted. ERC was repeated two and four weeks, respectively, after the RFA to identify BBS. After the strictures were identified, histologic evaluations were performed. On the follow-up ERC two weeks after the procedure, a segmental bile duct stricture was observed in all animals. On microscopic examination, severe periductal fibrosis and luminal obliteration with transmural inflammation were demonstrated. Bile duct perforations occurred in two pigs (100 W, n = 1; 80 W, n = 1) but there were no major complications in the 60 W group. The application of endobiliary RFA with 60 W electrical power resulted in a safe and reproducible swine model of BBS., Graphical Abstract

A reproducible in vivo swine model of bile duct dilation (BDD) was recently established and reported for the preclinical testing of newly developed biliary devices or endoscopic techniques. The aim of this study is to develop more advanced large animal model which is possible to direct examination of the biliary tree. Six mini pigs were prepared for the study. The BDD models were first made by closure of the ampulla of Vater in all swine. Then endoscopic papillary balloon dilation (EPBD) was performed in the animals. The feasibility of single-operator peroralcholangioscopy without assistance of accessories was evaluated using an ultra-slim upper endoscope in the animals. EPBD could be implemented using a dilation balloon catheter (10 ~ 13.5 mm) in all BDD models (6/6, 100%). The success rate of free-hand direct insertion of an ultra-slim endoscope into the common bile duct (CBD) was 100% (6/6), and access to the common hepatic duct with examination was possible using the direct peroralcholangioscopy in five animals (5/6, 83.3%). None of the animals died. In the cholangioscopic examination, a bile duct polyp and a benign biliary stricture occurred naturally, respectively, in two of six swine. An in vivo swine model of biliary dilatation-based direct peroralcholangioscopy was established. This novel animal model may be useful for the preclinical research of new materials or devices because direct visualization of the biliary tree is feasible. This article is protected by copyright. All rights reserved.

Surgery is the only curative treatment for cholangiocarcinoma, but even after surgery, survival rates are unsatisfactory. Recently, several reports have suggested microvascular invasion (MiVi) is associated with poor postoperative prognosis in hepatocellular carcinoma (HCC). We considered that MiVi might be associated with poor clinical outcomes in patients with surgically resectable cholangiocarcinoma. The records of 91 patients who underwent resection with curative intent for cholangiocarcinoma at Inha University Hospital from 2007 to 2017 were comprehensively reviewed for clinicopathological characteristics, DFS, and overall survival (OS) relations between these factors and the presence of MiVi. Forty-nine of the 91 study subjects had MiVi and 42 did not. Median overall survivals were 492 days in the MiVi group and 1008 days in the noMiVi group and median DFSs were 367 days and 760 days, respectively. Cumulative survival ratio and recurrence incidence rates were significantly different in the 2 groups (P = .012). Multivariable analysis showed the presence of MiVi was an independent risk factor of OS (hazard ratio [HR] 3.34; 95% confidence interval [CI], 1.40–7.97; P = .007). Cholangiocarcinoma is known to have a poor prognosis. When microvascular invasion remains after surgery it is associated with poor clinical outcomes.

Rationale: IgG4-related disease (IgG4-RD) is a systemic disease that can involve various organs and is characterized by the infiltrations of IgG4-positive plasma cells and lymphocytes, fibrosis, and elevated serum IgG4 levels. IgG4-related sclerosing cholangitis (IgG4-RSC) is a subtype of IgG4-RD. No certain relationship between IgG4-RSC and cholangiocarcinoma has been established as yet, and there have been few reports of the simultaneous diagnosis of IgG4-RSC and cholangiocarcinoma. Patient concerns: A 76-year-old male visited our gastroenterology department due to the recent occurrence of pruritus and jaundice. Diagnosis: Computed tomography (CT) scan showed ductal wall swelling and enhancement from both intrahepatic duct confluence to the common bile duct, upper biliary dilatation, and accompanying autoimmune pancreatitis (a sub type of IgG4-RD). Biopsy of the distal common bile duct by endoscopic retrograde cholangiopancreatography (ERCP) resulted in a diagnosis of IgG4-RSC. Subsequently, adenocarcinoma was identified by repeated cytology of bile juice. Finally, Klatskin tumor type IIIA and IgG4-RSC were concurrently diagnosed. Interventions: IgG4-RSC was treated with steroid and Klatskin tumors by gemcitabine + cisplatin chemotherapy. Outcomes: The jaundice had improved and CT showed substantial improvement of the intrahepatic duct dilatation. Lessons: IgG4-RSC and cholangiocarcinoma are easily confused, but their treatments are quite different, and thus, care must be taken during diagnosis. Furthermore, these 2 diseases may co-exist. Therefore, even if IgG4-RSC is diagnosed first, the possibility of accompanying cholangiocarcinoma should be thoroughly investigated.

Background and aims Catheter-based endobiliary radiofrequency ablation (RFA) is an endoscopic local treatment for patients with malignant biliary stricture (MBS). However, excessive heating of the bile duct by the current RFA system can induce serious complications. Recently, a new RFA system with automatic temperature control was developed. In the present study, we examined the safety of the new RFA system in patients undergoing endobiliary RFA for extrahepatic MBS. Methods This prospective, multicenter study enrolled patients with unresectable or inoperable extrahepatic (> 2 cm from the hilum) MBS. Endobiliary RFA was performed using a newly developed RFA catheter (ELRA™, STARmed, Goyang, Korea) at a setting of 7 or 10 W for 120 s and with a target temperature of 80°C. A self-expandable metallic stent was inserted after endobiliary RFA. The rate of procedure-related adverse events was assessed. Results The 30 patients were enrolled in this study. Cholangiocarcinoma was diagnosed in 19 patients, pancreatic cancer was found in 9, and gallbladder cancers were recorded in 2. The mean stricture length was 22.1 ± 6.6 mm. Post-procedural adverse events occurred in three patients (10.0%; 2 mild pancreatitis and 1 cholangitis) without hemobilia and bile duct perforation. The pancreatitis and cholangitis resolved with conservative treatment. The cumulative duration of stent patency and survival were 236 and 383 days, respectively. Conclusions Automatic temperature-controlled endobiliary RFA using a newly developed catheter was safely applied in patents with extrahepatic MBS. Further prospective studies are needed to confirm the efficacy of endobiliary RFA for MBS.

Background/Aims: Radiopaque metal markers are required to improve X-ray absorption by self-expandable metal stents (SEMSs) to enable precise stent placement. A new tantalum radiopaque marker was recently developed using an ultrasonic spray technique. The aim of the present study was to evaluate the safety and visibility of tantalum markers. Methods: A total of three beagle dogs were used for a gastrointestinal tract absorption test. Five tantalum markers were placed in the stomach of each dog endoscopically. Excreted tantalum markers were collected, and their weights were compared to the original weights. In radiopacity tests, marker radiopacities on X-ray images were quantified using ImageJ software and compared with those of commercially available metal markers. Finally, the radiographic images of six patients who underwent biliary SEMS placement using tantalum marker Nitinol SEMSs (n=3) or gold marker Nitinol SEMSs (n=3) were compared with respect to marker brightness on fluoroscopic images. Results: Absorption testing showed that the marker structures and weights were unaffected. Radiopacity tests showed that the mean brightness and total brightness scores were greater for tantalum markers (226.22 and 757, respectively) than for gold (A, 209 and 355, respectively; B, 204.96 and 394, respectively; C, 194.34 and 281, respectively) or platinum markers (D, 203.6 and 98, respectively). On fluoroscopic images, tantalum markers had higher brightness and total brightness scores (41.47 and 497.67, respectively) in human bile ducts than gold markers (28.37 and 227, respectively). Conclusions: Tantalum markers were found to be more visible than other commercially available markers in X-ray images and to be resistant to gastrointestinal absorption. (Gut Liver 2019;13:366-372)

Background Endoscopic papillary large balloon dilation (EPLBD) without prior endoscopic sphincterotomy (EST) produces excellent outcomes for the treatment of large common bile duct (CBD) stones. However, it remains unclear how the outcomes of EPLBD alone compare with those of EPLBD with EST. In this study, we assessed the safety and therapeutic outcomes of EPLBD with vs. without EST for the removal of large bile duct stones. Methods This prospective, multicenter study was conducted on 200 patients with bile duct stones of ≥ 10 mm in diameter. Patients were randomly assigned to an EPLBD alone group (n = 100) or an EPLBD with EST group (n = 100). These two groups were compared with respect to overall procedure-related adverse events, overall stone removal success rate, number of endoscopic sessions required for complete stone removal, need for mechanical lithotripsy, and total procedure time. Results The incidence of adverse events was not significantly different between the groups (EPLBD alone vs. EPLBD with EST: overall adverse events 6 % vs. 4 %, P = 0.75; pancreatitis 1 % vs. 3 %, P = 0.62). Overall success (P = 0.35), initial success (P = 0.28), and the need for mechanical lithotripsy (P = 0.39) were also similar between groups. Median total procedure time tended to be greater in the EPLBD alone group (20.5 minutes) than in the EPLBD with EST group (18 minutes; P = 0.08). Conclusion The therapeutic outcomes and adverse events of EPLBD alone for the removal of large bile duct stones were comparable to those of EPLBD with EST.

BACKGROUND/AIMS Large-animal benign esophageal stricture (BES) models are needed for the development of new endoscopic therapies and related devices. This study was undertaken to develop and compare swine BES models produced by radiofrequency ablation (RFA) or endoscopic submucosal tunnel dissection (ESTD). MATERIALS AND METHODS RFA and ESTD were each performed on three pigs. Follow-up endoscopy and esophagography were performed immediately after the procedures and then 2, 3, and 4 weeks later. Four weeks after the procedures, all animals were sacrificed, and gross and histologic examinations were performed. RESULTS BES was successfully achieved in both the RFA and ESTD groups, and all animals survived without any serious adverse events during the 4-week follow-up period. Mean procedural times were 9.3 min for RFA and 89.3 min for ESTD. ESTD caused long segment strictures whose average length was 4.5 cm, whereas RFA produced short strictures whose average length was 1.4 cm. BES began to form 2 weeks after both procedures. Degrees of strictures were similar at 3 and 4 weeks in the ESTD group; however, it started deteriorating over time in the RFA group. Histologic examinations showed that ESTD caused inflammation and fibrosis in the submucosal layer, whereas RFA induced extensive inflammation in the submucosal and muscularis propria layers. CONCLUSION BES was successfully achieved using RFA or ESTD in swine without serious complications. The methods have different characteristics; therefore, researchers should choose the method more appropriate for their purposes.