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Abstract Acute biliary pancreatitis (ABP) with cholangitis requires endoscopic retrograde cholangiopancreatography (ERCP) within 24 h to resolve ductal obstruction. However, this recommendation is based on the timing of emergency room (ER) visits. We wanted to determine the optimal timing of ERCP for ABP based on the timing of symptom onset, not the timing of the ER visit. We retrospectively reviewed 162 patients with ABP with cholangitis who underwent urgent ERCP (within 24 h of ER admission). Area under the receiver operating characteristic (ROC) curve (AUC) was analyzed to determine differences in complication rates according to time from symptom onset. A difference in ERCP-related adverse events (AEs) was identified, and Youden’s J statistic was used to determine a cutoff time from symptom onset (18 h). We compared mortality and complications based on this cutoff. Based on time to symptom onset, significantly higher rates of aspiration pneumonia (odds ratio [OR] 4.00, 95% confidence interval [CI] 1.15–13.92, P = 0.021) and post-ERCP hypotension (OR 11.9, 95% CI 1.39–101.33, P = 0.005) were observed in the ≤ 18-h group than in the > 18-h group. The study found that patients who underwent ERCP within 18 h of symptom onset is associated with an increased risk of ERCP-related AEs.

Background: Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure. Objectives: We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC. Design: Multicenter, retrospective cohort study. Methods: This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes. Results: Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0–8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9–3.2). An albumin level of3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126). Conclusion: An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders.

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE. Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed. Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance. Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS.Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively.Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p

Background/Aims: Acute pancreatitis (AP) is a common gastrointestinal disease associated with hospitalization. With the increase in its incidence, AP has become a greater burden on healthcare resources. Early identification of patients with mild AP can facilitate the appropriate use of resources. We aimed to investigate the ability of inflammatory markers, including interleukin-6 (IL-6), procalcitonin, and C-reactive protein (CRP), as well as various scoring systems to differentiate mild AP from more severe diseases.Methods: We retrospectively investigated patients hospitalized with AP, for whom severity assessment and clinical course confirmation were possible. Inflammatory markers were measured at admission, and CRP levels were measured 24 hours after admission (CRP2). Predictive values were calculated using the area under the receiver operating characteristic curve (AUROC) and logistic regression model analysis.Results: Of 103 patients with AP, 42 (40.8%) were diagnosed with mild AP according to the revised Atlanta classification. Based on the AUROC, IL-6 (0.755, p

The serum level of CA 19-9 is a prognostic marker for pancreatic ductal adenocarcinoma (PDAC). We evaluated the ability of the expression level of methionyl-tRNA synthetase 1 (MARS1)—which facilitates cancer growth by modulating protein synthesis and the cell cycle—to predict the prognosis of PDAC. Immunohistochemical (IHC) staining was performed on pancreatic specimens obtained from patients with PDAC who were undergoing surgery. High MARS1 expression was defined as equal to, or greater than, that in normal acinar cells. Low MARS1 expression was defined as weaker than in normal acinar cells, and stronger than in the pancreatic duct epithelium. Univariate and multivariate analyses were performed on other factors related to prognosis. Among 137 PDAC patients, no significant differences in baseline characteristics were found between those with high (n = 82) and low (n = 55) MARS1 expression. The median overall survival time of patients with high MARS1 expression was shorter than that of those with low expression (15.2 versus 17.2 months, log-rank test p = 0.044). The median disease-free survival (DFS) was not significantly different between the two groups. However, the DFS was shorter in patients with high than in those with low MARS1 expression (8.9 versus 11.2 months, log-rank test p = 0.067). In a multivariate analysis, lymph node metastasis and high MARS1 expression were associated with a poor prognosis of PDAC. Elevated MARS1 expression detected by IHC staining is associated with a poor prognosis of PDAC, suggesting that MARS1 has potential as a prognostic marker.

Abstract The use of endobiliary radiofrequency ablation (RFA) to generate a benign biliary stricture (BBS) model has a significant reproducibility problem. The aims of this animal study were to create an optimal BBS model using endobiliary RFA and determine the best way to develop it. The first step was performed on the common bile duct (CBD) of 10 miniature pigs using endoscopic RFA with a target temperature-controlled mode (80 ℃, 7 W for 90 s). The second step was performed on the CBD of five miniature pigs to understand more about the time-dependent changes in BBS development and the causes of adverse events. Using the conditions and techniques identified in the previous steps, the third step was conducted to create an optimal BBS model in 12 miniature pigs. In the first trial, four out of 10 animals died (40%) after the procedure due to cholangitis-induced sepsis. Based on this, biliary obstruction was prevented in further steps by placing a biliary plastic stent after RFA application. Histologic examinations over time showed that a severe abscess developed at the RFA application site on the fifth day, followed by fibrosis on the tenth day, and completion on the twentieth day. In the third trial, 11 animals survived (91.7%), the average BBS fibrotic wall thickness was 1107.9 µm (763.1–1864.6 µm), and the degree of upstream biliary dilation was 14.4 mm (11.05–20.7 mm). In conclusion, endobiliary RFA combined with a biliary plastic stent resulted in a safe and reproducible BBS animal model.

Abstract Treatment of benign biliary strictures (BBS) using fully covered self-expandable metal stents (FCSEMS) has a high success rate, but recurrence can occur. Corticosteroids may be useful based on their anti-fibrotic and anti-inflammatory effects. We investigated the safety and efficacy of corticosteroid-eluting FCSEMS in an animal model. BBSs were created by radiofrequency ablation in 12 mini-pigs. Four weeks later, FCSEMS coated with 0 mg (control), 15 mg (steroid 1 × group), or 30 mg (steroid 2 × group) triamcinolone were inserted endoscopically. The in vitro drug release assay revealed that the optimal stent had 15 mg of triamcinolone and a hydrophilic membrane. No transmural necrosis or perforation occurred in any animal. Fibrous wall thickness tended to decrease macroscopically and microscopically in a triamcinolone dose-dependent manner (control vs. steroid 2 × group: 773.1 vs. 468.5 µm, P = 0.037). Thickness also decreased over time in the steroid 2 × group (3 days vs. 4 weeks: 907.9 vs. 468.5 µm, P = 0.025). Blood parameters tended to improve after stent insertion. In a porcine BBS model, steroid-eluting FCSEMS showed potential as a safe and effective treatment modality to reduce fibrotic tissue. Studies are required to confirm their safety and efficacy in humans with refractory BBS.

Background/Aims: Sphincterotomes are essential for endoscopic sphincterotomy (EST) and can also be used for cannulation in ERCP. A domestic new pull-type sphincterotome (Optimos™, Taewoong, Goyang, Korea) provides acceptable technical feasibility and safety, but there are no comparison results. Thus, this study compared the clinical performance and safety of Optimos™ sphincterotome to a conventional sphincterotome (CleverCut3™, Olympus, Tokyo, Japan) in patients who underwent ERCP. Methods: From April 2021 to July 2021, a randomized prospective comparative study was conducted on 104 consecutive patients who underwent ERCP in three medical centers. The primary endpoint was the clinical performance and safety of sphincterotomes during ERCP. Results: One hundred and four patients were assigned randomly to the Optimos™ group (n=51) or CleverCut3™ group (n=53). All demographic characteristics did not differ between the groups except the BMI. The technical success rate for cannulation, performance of EST, and total procedure time were similar in the two groups. The adverse events did not differ, even though two cases of post-ERCP pancreatitis occurred in CleverCut3™. On the other hand, in questionnaire analysis, CleverCut™ showed a better user’s convenience (median [interquartile range] 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.013) and manipulability (median [interquartile range], 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.039) than Optimos™, even though the other profiles did not reveal any differences. Conclusions: New domestic pull-type sphincterotome can offer comparable clinical performance and safety profiles to conventional sphincterotome, but it needs refinements to increase the user’s convenience and manipulability. Further improvement and innovation will be required to advance domestic medical devices.

Malignant biliary strictures are caused by pancreatobiliary cancer and other metastatic malignancies. Most of them are unresectable at diagnosis with a dismal prognosis. Various new ablation methods have been introduced. Of them, ERCP-guided intraductal radiofrequency ablation (ID-RFA) appears to be the most promising minimally invasive endoscopic treatment by delivering a high-frequency alternating current to the target tissue, leading to coagulative necrosis. Thus far, many studies have provided evidence that ERCP-guided ID-RFA is a safe, feasible, and effective treatment modality for stent patency and overall survival. Compared to other ablation treatments, ERCP-guided ID-RFA has several advantages, including ease of delivery, controlled application of thermal energy, low cost, and fewer systemic side effects with an acceptable safety profile. Therefore, ERCP-guided ID-RFA can be considered an adjunctive treatment for the palliation of unresectable malignant biliary strictures. On the other hand, the decision of local ablation treatment should be individualized by multidisciplinary team support due to the lack of comparative studies.

Background and Aims: Various guidewires are used for biliary cannulation, and each one has its own characteristics affecting its effectiveness. This study aimed to measure the basic properties and evaluate the effectiveness of a newly developed 0.025-inch guidewire for selective biliary cannulation. Methods: A total of 190 patients at five referral hospitals were randomly allocated to undergo selective biliary cannulation using the newly developed guidewire (NGW group, n = 95) or a conventional guidewire (CGW group, n = 95). The primary outcome was the selective biliary cannulation rate in naïve papillae. The secondary outcome was to measure the NGW basic properties, compare them with those of the CGW, and analyze the importance of basic property differences. Results: There were no significant differences between the groups in the baseline characteristics. The primary outcome (75.8% vs. 84.2%, p = 0.102) and adverse event rate (6.3% vs. 4.2%, p = 0.374) were similar in both groups. However, compared with the CGW group, the NGW group showed a higher number of ampulla contacts (2.58 vs. 2.02, p = 0.011) and longer cannulation time (216.5 vs. 135.1 s, p = 0.016). Furthermore, the NGW group had higher maximum friction (34.6 ± 1.34 vs. 30.2 ± 4.09), lower stiffness, and better elastic resiliency. In the multivariate analysis, a curved-tip GW (OR = 0.26, 95% CI 0.11–0.62, p = 0.002) and normal papillary shape (OR = 0.39, 95% CI 0.17–0.86, p = 0.021) were contributing factors for successful selective biliary cannulation. Conclusions: The NGW group had high friction and low stiffness, characteristics affecting biliary cannulation. Clinically, the NGW group had similar success and adverse event rates as the CGW, but they showed a higher number of ampulla contacts and longer cannulation time.

Pancreatobiliary malignancy is relatively rare; however, it remains one of the most lethal malignancies and has a dismal prognosis. Endoscopic retrograde cholangiopancreatography (ERCP)-guided intraductal radiofrequency ablation (ID-RFA) is a promising, minimally invasive treatment for unresectable malignant biliary strictures by delivering high-frequency alternating current to the target tissue, leading to coagulative necrosis. Recent studies have provided evidence that ERCP-guided ID-RFA is a safe, well-tolerated, and effective adjunctive treatment in terms of stent patency as well as overall survival. Compared with other local treatments, such as photodynamic therapy, ERCP-guided ID-RFA has advantages, including ease of delivery, controlled application of thermal energy, low cost, and fewer systemic side effects, with an acceptable safety profile. ERCP-guided ID-RFA has been proposed as an attractive endobiliary ablative therapy and is regarded to be an adjuvant method for the palliative care of patients with unresectable malignant biliary strictures. However, due to the ongoing lack of comparative studies, the choice of local ablative therapy remains, in each case, an individual decision by the multidisciplinary team.

Radiofrequency ablation (RFA) has been regarded as an established technique to treat various diseases such as hepatocellular carcinoma, renal cell carcinoma and Barret’s esophagus. Although the application of RFA in the pancreas has been limited due to increased risk of adverse events, endoscopic ultrasound-guided RFA (EUS-RFA) has generated interest as a novel minimally invasive treatment modality which combines real-time visualization with a precise localization of the treatment procedure. For over a decade, the optimization of RFA devices have made EUS-RFA relatively safe, and several studies have supported its feasibility. However, there is insufficient evidence to suggest the appropriate indications and to describe long-term outcomes of EUS-RFA for various pancreatic neoplasms such as pancreatic neuroendocrine tumor, ductal adenocarcinoma, and cystic lesions. Therefore, this review focuses on the technical aspects and clinical applications of EUS-RFA for each pancreatic disease.

A gallbladder (GB) polyp is an elevation of the GB mucosa that protrudes into the GB lumen. GB polyps have an estimated prevalence of 0.3-9.5% and can be divided into neoplastic (true) polyps and nonneoplastic polyps (pseudopolyps). Pseudopolyps are most commonly cholesterol polyps but also include focal adenomyomatosis and inflammatory polyps with no malignant potential. Neoplastic polyps, however, can be benign or malignant. Benign polyps are most commonly adenomas, while malignant polyps are usually adenocarcinoma. Transabdominal ultrasonography is the main radiological modality used for diagnosing and surveilling GB polyps. On the other hand, because it is difficult to diagnose GB polyps before surgery, alternative imaging modalities, such as endoscopic ultrasound, are being further evaluated. The current guidelines recommend cholecystectomy for GB polyps ≥ 10 mm in size as well as suboptimal sized GB polyps (6-9 mm) with other risk factors, including age >50, sessile, and symptoms. The quality of the evidence behind this practice is relatively low. Therefore, this review identifies the current gaps in the available evidence and guidelines and introduces methods that can help make decisions regarding patients who require a cholecystectomy or follow-up.

A number of different conditions can lead to a bile duct stricture. These strictures are particularly common after biliary operations, including living-donor liver transplantation. Endoscopic and percutaneous methods have high success rates in treating benign biliary strictures. However, these conventional methods are difficult to manage when a guidewire cannot be passed through areas of severe stenosis or complete obstruction. Magnetic compression anastomosis has emerged as an alternative nonsurgical treatment method to avoid the mortality and morbidity risks of reoperation. The feasibility and safety of magnetic compression anastomosis have been reported in several experimental and clinical studies in patients with biliobiliary and bilioenteric strictures. Magnetic compression anastomosis is a minimally traumatic and highly effective procedure, and represents a new paradigm for benign biliary strictures that are difficult to treat with conventional methods.

Background/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy (SAA) is challenging to gastrointestinal endoscopists. The aim of this study was to evaluate the impact of scope exchange from a long single balloon enteroscope (SBE) to a gastroscope during SBE-assisted ERCP (SBE-ERCP) in patients with SAA. Methods: Patients who underwent SBE-ERCP between February 2019 and October 2020 were retrospectively identified. Intubation success, scope exchange success, cannulation success, and therapeutic success were analyzed along with complications. Results: Fifty-six patients with various SAAs underwent SBE-ERCP procedures, including Billroth II subtotal gastrectomy (B-II, n=13), pylorus-preserving pancreato-duodenectomy (PPPD, n=6), Roux-en-Y hepaticojejunostomy (REY HJ, n=4), and total gastrectomy with REY anastomosis (TG REY, n=33). Overall intubation, cannulation, and therapeutic success rates were 89.3%, 82.1%, and 82.1%, respectively. Therapeutic success rates did not differ significantly among the type of SAA. Successful scope exchange rate after successful intubation was significantly higher in native papilla (B-II and TG REY, 83.3%, 35/42) compared to bilioenteric anastomosis (PPPD and REY HJ, 0%, 0/8, p

Liver transplantation (LT) is a viable treatment for fatal end-stage liver disease. Anastomotic bile leakage and anastomotic stricture are considered as major post-LT complications. Stent insertion by endoscopic retrograde cholangiopancreatography and percutaneous transhepatic biliary drainage is the conventional treatment for post-LT anastomotic biliary stricture. In cases in which these conventional modalities fail, magnet compression anastomosis (MCA) can be applied. We reported a case in which post-LT bile leakage and anastomotic stricture were treated by MCA and using a fully covered self-expandable metal stent (FCSEMS). The FCSEMS was removed 3 months later, at which time the stricture and the leakage had resolved.

Background/AimsMetallic 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.Conclusion : sIn 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.

Refractory functional dyspepsia (RFD) is diagnosed when symptoms persist for at least 6 months despite at least two medical treatments. No consensus treatment guidelines exist. The implicated causes of functional biliary dyspepsia are a narrowed cystic duct, Sphincter of Oddi dysfunction, microlithiasis, and gallbladder dyskinesia. We investigated the treatment effects of litholytic agents. RFD patients were prospectively enrolled in six tertiary medical centers. All subjects took chenodeoxycholic and ursodeoxycholic acids (CNU) twice daily for 12 weeks. We monitored their medication adherence, laboratory results, and complications. The 7-point global symptom scale test scores were determined before and after treatment. Of the 52 patients who were prospectively screened, 37 were included in the final analysis. The mean age was 51.3 years: 14 were males, and 23 were females. Before treatment, the mean number and duration of symptoms were 2.4 and 48.2 months, and a mean of 3.3 FD-related drugs were taken. The mean CNU adherence was 95.3%. The mean global symptom scale score decreased from 5.6 pretreatment to 2.6 posttreatment. The symptom improvement rate was 94.6% (35 out of 37 patients). The only adverse event was mild diarrhea (10.8%) that was resolved after conservative management. Conclusions: CNU improved the symptoms of RFD patients who did not respond to conventional medications. Litholytic agents are good treatment options for patients with RFD and biliary dyspepsia secondary to biliary microlithiasis. Further prospective, large-scale mechanistic studies are warranted.

Self-expandable metallic stents (SEMSs) are typically inserted in patients with unresectable malignant biliary obstruction. However, SEMSs are susceptible to occlusion. To overcome this issue, we developed a large-bore, dumbbell-shaped, fully covered SEMS (FCSEMS-L) and compared its efficacy and safety with those of a conventional FCSEMS (FCSEMS-C) in patients with malignant biliary obstruction. Methods: Patients with unresectable distal malignant biliary obstruction were retrospectively enrolled between January 2011 and February 2021. All patients underwent endoscopic insertion of FCSEMSs. Recurrent biliary obstruction (RBO), patient survival time, complications, and prognosis were analyzed. Results: RBO occurred in 31 patients (35.6%) who received an FCSEMS-L, and in 34 (45.9%) who received an FCSEMS-C. Stent occlusion occurred in 19 patients (21.8%) who received an FCSEMS-L, and in 22 (29.7%) who received an FCSEMS-C. Stent migration occurred in 12 patients (13.8%) with an FCSEMS-L and 12 (16.2%) with an FCSEMS-C. The median time to RBO (TRBO) was 301 days with an FCSEMS-L and 203 days with an FCSEMS-C. The median survival time was 479 days with an FCSEMS-L and 523 days with an FCSEMS-C. The TRBO and patient survival time did not significantly differ between the two groups. Conclusions: There were no significant differences in efficacy and complication rates between the fully covered large bore SEMSs and conventional fully covered SEMSs.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a precancerous lesion of cholangiocarcinoma, for which surgical resection is the most effective treatment. We evaluated the predictors of malignancy in IPNB according to anatomical location and the prognosis without surgery. Methods: A total of 196 IPNB patients who underwent pathologic confirmation by surgical resection or endoscopic retrograde cholangiography or percutaneous transhepatic cholangioscopic biopsy were included. Clinicopathological findings of IPNB with invasive carcinoma or mucosal dysplasia were analyzed according to anatomical location. Results: Of the 116 patients with intrahepatic IPNB (I-IPNB) and 80 patients with extrahepatic IPNB (E-IPNB), 62 (53.4%) and 61 (76.3%) were diagnosed with invasive carcinoma, respectively. Multivariate analysis revealed that mural nodule > 12 mm (p = 0.043) in I-IPNB and enhancement of mural nodule (p = 0.044) in E-IPNB were predictive factors for malignancy. For pathologic discrepancy before and after surgery, IPNB has a 71.2% sensitivity and 82.3% specificity. In the non-surgical IPNB group, composed of nine I-IPNB and seven E-IPNB patients, 43.7% progressed to IPNB with invasive carcinoma within 876 days. Conclusions: E-IPNB has a higher rate of malignancy than I-IPNB. The predictive factor for malignancy is mural nodule > 12 mm in I-IPNB and mural nodule enhancement in E-IPNB.

We evaluated the proportion of BRCA 1/2 germline mutations in Korean patients with sporadic pancreatic ductal adenocarcinoma (PDAC) and its effect on the chemotherapeutic response of FOLFIRINOX. This retrospective study included patients who were treated at two tertiary hospitals between 2012 and 2020, were pathologically confirmed to have PDAC, and had undergone targeted next-generation sequencing-based germline genetic testing. Sixty-six patients were included in the study (24 men; median age 57.5 years). In the germline test, BRCA 1/2 pathogenic mutations were found in nine patients (9/66, 13%, BRCA 1, n = 3; BRCA 2, n = 5; and BRCA 1/2, n = 1). There was no significant difference in the baseline characteristics according to BRCA mutation positivity. Among patients who underwent FOLFIRINOX chemotherapy, patients with a BRCA 1/2 mutation showed a higher overall response rate than those without a BRCA 1/2 mutation (71.4% vs. 13.9%, p = 0.004). Patients with a germline BRCA 1/2 mutation showed longer progression-free survival than those without a BRCA 1/2 mutation, without a significant time difference (18 months vs. 10 months, p = 0.297). Patients with a BRCA 1/2 mutation in the germline blood test had a higher response rate to FOLFIRINOX chemotherapy in PDAC. The high proportion of BRCA 1/2 germline mutations and response rate supports the need for germline testing in order to predict better treatment response.

Common bile duct (CBD) stone is a biliary disease with an increasing incidence in Korea. Many advances have been made in diagnosis and treatment according to the development of imaging equipment and various devices to diagnose and treat CBD stones. The Korean Society for Pancreatobiliary Association has developed clinical practice guidelines for the diagnosis and treatment of CBD stones to assist clinicians in their management. The guidelines were divided into three parts: evaluation of CBD stones, endoscopic management of CBD stones, and endoscopic management of difficult and recurrent CBD stones. The purpose of this review is to summarize and present the diagnosis and treatment guidelines for CBD stones established in Korea.

Biliary-tract complications, such as biliary strictures, anastomotic leaks, choledocholithiasis, and biliary casts, can occur after liver transplantation (LT). Of these complications, biliary strictures are regarded as an Achilles’ heel. Recently, treatment of anastomotic biliary stricture (ABS) has transitioned from conventional surgical revision to a nonsurgical treatment modality. Endoscopic serial balloon dilatation and/or multiple plastic stent replacements are highly effective and are now regarded as the first-line treatments. However, if the patient has undergone anastomosis by means of a hepaticojejunostomy, percutaneous treatment is performed. With recent technological advances and the rendezvous method, the clinical success rates of endoscopic and percutaneous ABS treatments have increased, but these methods fail in some patients who have total obstruction of anastomotic stricture. For these patients, magnetic compression anastomosis (MCA) has been suggested as an alternative method. Animal and human studies have demonstrated the safety and efficacy of MCA, and advancements in these nonsurgical methods have increased the clinical success rate of ABS. This review focuses on ABSs that develop after LT and discusses the clinical results of various nonsurgical methods and future directions.

(1) Background: Pancreatic cancer is a high devastating disease with the lowest survival rate among all common cancers due to difficulties in early diagnosis. The purpose of this study was to identify and characterize the distinct subset of blood cell population elevated in peripheral blood mononuclear cells (PBMC) of pancreatic cancer to evaluate the potential markers for diagnosis of pancreatic cancer; (2) Methods: We analyzed differential gene expression in PBMC from normal individuals and pancreatic cancer patients utilizing transcriptome analysis. Flow cytometry analysis was applied to identify the discrete subset of interleukin-7 receptor (IL-7R) expressing cells in these cells. The expression of IL-7R during tumorigenesis was determined in syngeneic mouse model of pancreatic cancer in vivo; (3) Results: PBMC from pancreatic cancer patients expressed elevated IL-7R mRNA compared to healthy control individuals. IL-7R expressing cells rapidly appeared from the early stages of the onset of tumor formation in syngeneic pancreatic cancer mouse model in vivo. The discrete subset of IL-7R positive cells mainly consist of naive T, central memory T, and effector memory T cells; (4) Conclusions: Taken together, our present findings suggest that pancreatic cancer patients expressed higher level of IL-7R expression in PBMC that rapidly emerged from the onset of early pancreatic tumor formation in vivo than normal individuals. Thus, it can be used as a novel biological marker for early events of pancreatic cancer development.

Summary of Event: An endoscopic retrograde pancreatic duct (ERPD) stent was inserted in a male patient with chronic pancreatitis via endoscopic retrograde cholangiopancreatography (ERCP) to relieve chronic epigastric pain. After the procedure, an abdominal computed tomography scan showed localized peritonitis with a dislocated ERPD stent. The patient underwent an emergency operation, which revealed that the peritonitis was caused by perforation of the pancreatic parenchyma by the ERPD stent. Teaching Point: A hydrophilic guide wire can puncture the pancreas during ERPD stent insertion. Therefore, it is necessary to ensure that the guide wire reaches the main pancreatic duct, especially in patients with chronic pancreatitis.

Background/AimsA 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.Conclusion : sThere were no significant differences in stent patency or patient survival in MSCPM-II and CMS patients with malignant biliary obstructions.

Gemcitabine is clinically used to treat certain types of cancers, including pancreatic and biliary cancer. We investigated the signal transduction pathways underlying the local antitumor effects of gemcitabine-eluting membranes (GEMs) implanted in pancreatic/biliary tumor-bearing nude mice. Here, we report that GEMs increased the E3 ubiquitin ligase c-CBL protein level, leading to degradation of epidermal growth factor receptor (EGFR) in SCK and PANC-1 cells. GEMs decreased the RAS and PI3K protein levels, leading to a reduction in the protein levels of active forms of downstream signaling molecules, including PDK, AKT, and GSK3β. GEM reduced proliferation of cancer cells by upregulating cell cycle arrest proteins, particularly p53 and p21, and downregulating cyclin D1 and cyclin B. Moreover, GEMs reduced the levels of proangiogenic factors, including VEGF, VEGFR2, CD31, and HIF-1α, and inhibited tumor cell migration and invasion by inducing the expression of E-cadherin and reducing that of N-cadherin, snail, and vimentin. We demonstrated that local delivery of gemcitabine using GEM implants inhibited tumor cell growth by promoting c-CBL-mediated degradation of EGFR and inhibiting the proliferation, angiogenesis, and epithelial−mesenchymal transition of pancreatic/biliary tumors. Use of gemcitabine-eluting stents can improve stent patency by inhibiting the ingrowth of malignant biliary obstructions.

Background: Recently, there has been an increase in clinical success rates using nonsurgical methods to resolve anastomotic biliary strictures (ABSs) that develop after liver transplantation (LT). However, some strictures are particularly refractory and cannot be completely resolved by an endoscopic or percutaneous procedure. Consequently, the aim of this study was to examine the feasibility and efficacy of using a newly designed fully covered self-expandable metal stent (FCSEMS) to resolve refractory ABS. Methods: A total of 35 patients with an ABS that developed after LT, but could not be resolved by an endoscopic or percutaneous procedure, were included in this study. FCSEMSs were positioned endoscopically and removed after 2–3 months. After stent removal, the patients were followed to assess complications, including re-stenosis. Results: The mean period from LT to stricture was 13.7 months, and the mean duration of the stricture was 31.8 months. The type and mean number of procedures previously attempted were endoscopic retrograde cholangiopancreatography (ERCP) (9.1 ± 5.1) in 19 patients and percutaneous transhepatic biliary drainage (9.2 ± 4.8) in 16 patients. All patients had successful FCSEMS insertions and removals; the mean stent indwelling time was 3.2 months. The mean follow-up period was 18.7 months (range: 6.4–37.8 months). Stricture recurrence was observed in 6 of 29 patients (recurrence rate: 20.7%). The anastomotic stricture resolved with the FCSEMS insertion in 29 of 35 patients (clinical success rate: 82.9%). Conclusions: The newly designed FCSEMS is a potentially feasible and effective treatment for anastomotic strictures that develop after LT but are not amenable to treatment by conventional procedures.

Endoscopic ultrasonography (EUS) technology has undergone a great deal of progress along with the color and power Doppler imaging, three-dimensional imaging, electronic scanning, tissue harmonic imaging, and elastography, and one of the most important developments is the ability to acquire contrast-enhanced images. The blood flow in small vessels and the parenchymal microvasculature of the target lesion can be observed non-invasively by contrast-enhanced EUS (CE-EUS). Through a hemodynamic analysis, CE-EUS permits the diagnosis of various gastrointestinal diseases and differential diagnoses between benign and malignant tumors. Recently, mechanical innovations and the development of contrast agents have increased the use of CE-EUS in the diagnostic field, as well as for the assessment of the efficacy of therapeutic agents. The advances in and the current status of CE-EUS are discussed in this review.

Implantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We reported recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an animal model. However, little is known about the molecular mechanisms by which paclitaxel-eluting stents attenuate tumor growth. We investigated the signal transduction pathways underlying the antiproliferative effects of a paclitaxel-eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted pancreatic/cholangiocarcinoma xenograft tumors by Western blot, immunoprecipitation, and immunofluorescence. The quantities of paclitaxel released into the tumor and plasma were determined by liquid chromatography-tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the tumor inhibited angiogenesis, which involved suppression of mammalian target of rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal interaction-related expression of proteins such as CD44, SPARC, matrix metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway.