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The emergence of glucocorticoid-responsive autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC), a new disease entity, has attracted considerable interest within the international gastroenterology community. The typical manifestations of AIP/IgG4-SC are obstructive jaundice and pancreatic enlargement in the elderly, which may mimic the presentations of pancreatobiliary malignancies. The timely diagnosis of AIP/IgG4-SC can lead to adequate glucocorticoid treatment, whereas a misdiagnosis can result in unnecessary major surgery. The diagnostic criteria used to diagnose AIP include several cardinal features of AIP that can be detected via pancreatic parenchymal imaging, ductal imaging, serum IgG4 levels, histopathology, other organ involvement, and response to glucocorticoid therapy. The differential diagnosis of AIP/IgG4-SC may include pancreatobiliary malignancies and primary sclerosing cholangitis. Although most patients with AIP/IgG4-SC respond well to glucocorticoid therapy, there is a frequent relapse of the disease in the long term. This review describes the evolution of the concept of AIP and IgG4-related disease, including the development of diagnostic criteria, discusses the current practice for diagnosis and treatment, and suggests prospects for research.

The diagnosis of type 2 autoimmune pancreatitis (AIP) is dependent on typical radiologic imaging and the presence of the granulocytic epithelial lesion (GEL), which is characterized by ductal neutrophilic infiltration with or without neutrophilic acinar infiltration.We evaluated GEL and related clinicopathologic factors in 165 resected heterotopic pancreata (HPs) [57 gastric (35%), 56 duodenal (34%), 30 omental (18%), and 22 jejunal (13%)] and 29 matched orthotopic pancreata routinely examined during surgery.GEL was noted in 8% (13/165) of HPs, including ductal epithelial (6/13, 46%) and intraluminal (8/13, 62%) neutrophilic infiltrations. However, there was no GEL in orthotopic pancreata. Abdominal pain was observed in 6 (46%) patients with GEL-positive HPs. GEL was more commonly observed in HPs having symptoms (p = 0.029), a larger size (p = 0.028), and an infiltrative growth pattern (p = 0.006). In addition, periductal lymphoplasmacytic infiltration and fibrosis (both p 0.001), interstitial fibrosis (p = 0.017), acinar neutrophilic infiltration (p = 0.032), venulitis (p = 0.050), acinar ductal metaplasia (ADM; p = 0.040), and pancreatic intraepithelial neoplasia/intraductal papillary mucinous neoplasms (PanIN/IPMN; p 0.001) were more commonly seen in HPs with GEL than in those without GEL. Inflammatory bowel disease was present only in one patient with GEL-negative HP.GELs are detected in a subset of HPs without clinical evidence of AIP. Therefore, for the diagnosis of AIP, GEL should be carefully interpreted with the context of other histologic, clinical, and radiologic findings.

EUS-guided transluminal drainage (EUS-TD) is increasingly used for the treatment of postoperative pancreatic fluid collections (POPFCs). A novel lumen-apposing metal stent (LAMS) was recently developed and used for the drainage of POPFCs. This study aimed to evaluate the efficacy and safety of a novel LAMS in patients with POPFCs.Forty-seven patients with symptomatic POPFCs who underwent EUS-TD with a novel LAMS (Niti-S SPAXUS; Taewoong Medical Co, Ltd, Ilsan, South Korea) between April 2019 and July 2020 were included in this study. Clinical outcomes, including technical success, clinical success, and adverse events, were retrospectively evaluated.EUS-TD was technically successful in 41 of 47 patients (87.2%). Clinical success was achieved in 37 of 41 patients (90.2%). The mean procedure time was 13.7 ± 3.5 minutes. The mean POPFC size was 59 ± 18.9 mm. The mean time interval from surgery to EUS-TD was 24.2 ± 37.6 days. Five patients experienced 6 procedural adverse events (12.8%): 4 (8.5%) POPFC infections and 2 (4.3%) distal stent migrations. The 4 patients with POPFC infection underwent additional endoscopic interventions. Of the 2 patients with stent migration, 1 underwent laparoscopic exploration and surgical extraction of the stent and 1 (2.1%) experienced POPFC recurrence, which was managed with percutaneous drainage.EUS-TD for symptomatic POPFCs with a novel LAMS is technically feasible and effective, with an acceptable adverse event rate. Further larger-scale prospective studies are required to confirm the findings of this study.

Background and Aims Endoscopic ultrasound-guided through-the-needle biopsy (EUS-TTNB) using microbiopsy forceps is performed for the accurate diagnosis of pancreatic cystic lesions (PCLs). However, there are no standardized protocols for this procedure, and the amount of data on its efficacy is limited. Here, we evaluated the feasibility, efficacy, and safety of EUS-TTNB in categorizing the types of PCLs, and identified the factors associated with diagnostic failure. Methods The prospectively collected and maintained EUS-TTNB database at Asan Medical Center was reviewed to identify patients with PCL who underwent EUS-TTNB between January 2019 and January 2021. The primary outcomes were technical success, diagnostic yield, and adverse events. Factors contributing to diagnostic failure, and the discrepancies in the diagnosis made by conventional modalities (ie, EUS-morphology, cross-sectional imaging, and cystic fluid analysis) were also evaluated. Results A total of 45 patients were analyzed. EUS-TTNB was successfully performed in all patients (technical success = 100%). Histologic diagnosis of PCL was made in 37 patients (diagnostic yield = 82%). When comparing EUS-TTNB with presumptive diagnosis, EUS-TTNB changed the diagnosis in 10 patients in terms of the categorization of the types of PCLs. The diagnostic yield was significantly higher in those who had 4 or more visible biopsy specimens per session (93%) than in those with less than 4 visible biopsy specimens per session (67%; P = .045). During follow-up, 3 (7%) patients experienced adverse events (2 acute pancreatitis, 1 intracystic bleeding), and no life-threatening adverse event occurred. Conclusions EUS-TTNB showed high technical feasibility, diagnostic yield, and good safety profile. EUS-TTNB may improve the categorization of the types of PCLs. Studies with standardized procedure protocols are needed to reduce the diagnostic failure for the types of PCLs.

Background Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) can be used for the differential diagnosis of pancreatic lesions by evaluating microvascular circulation and patterns of contrast enhancement. However, routine use of CEH-EUS is limited by its high cost, the lack of contrast agent availability and the absence of expertise with this technique. Directional eFLOW (D-eFLOW) (Aloka Co., Ltd., Tokyo, Japan) was introduced as a new high-definition modality that detects blood flow in microvessels. Because it uses built-in functions, it entails no additional cost and reduces time for examination. The present study compared the usefulness of D-eFLOW and CEH-EUS for differential diagnosis of pancreatic and peripancreatic lesions. Methods This retrospective study analyzed 130 patients who underwent EUS and D-eFLOW examinations from January 2016 to March 2020 to evaluate pancreatic and peripancreatic masses. Results All 130 patients underwent D-eFLOW and CEH-EUS examinations. Histological diagnoses were confirmed in 130 patients by EUS-FNA and/or surgery. D-eFLOW and CEH-EUS showed good correlation in evaluating the vascularity of pancreatic and peripancreatic tumors (Fisher's exact test, p Conclusions In evaluating the characteristics of tumorous lesions, vascularity detected by D-eFLOW showed good correlation with enhancement patterns of CEH-EUS. D-eFLOW can be considered a good alternative to CEH-EUS in diagnosing pancreatic and peripancreatic masses.

Background Retroperitoneal neurogenic tumors are extremely rare pathological entities; therefore, few clinical features and natural courses, especially originating from the pancreatic/peripancreatic regions, have been reported. This study aimed to investigate the clinicopathological features of pancreatic and peripancreatic neurogenic tumors and assess the diagnostic value of computed tomography (CT) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). Methods Between 2006 and 2018, patients who were diagnosed with neurogenic tumors were included. In total, 90 histologically confirmed cases of neurogenic tumors located in the pancreatic/peripancreatic regions were selected for analysis. Results The mean age was 49.2 ± 13.1 years. There were no differences in sex distribution of the tumors. Schwannomas (44.4%) and paragangliomas (41.1%) were the most common neurogenic tumors. The sensitivity of CT was 62.2% in 90 cases. EUS-FNB was performed in 30 cases and the sensitivity of it was 83.3%. The diagnosis of neurogenic tumors with EUS-FNB or CT was not significantly associated with tumor location and size. Surgical resection was performed in 78 cases. Of the 12 patients who did not undergo surgery, 10 cases were followed-up without any increase in tumor size. Conclusions Through the present study, we verified radiological, pathological, and clinical aspects of the pancreatic/peripancreatic neurogenic tumors which little known before, therefore, this study can serve as the basis for research to present an optimal diagnosis and treatment of neurogenic tumors. In addition, EUS-FNB is useful in the diagnosis of pancreatic/peripancreatic neurogenic tumors with relatively high sensitivity and can help establish therapeutic plans before the surgery.

EB-RFA with self-expandable metal stent (SEMS) may improve the stent patency and patient survival in malignant extrahepatic biliary obstruction. However, there are few studies on the role of EB-RFA for malignant hilar obstruction (MHO). This study aimed to assess the feasibility, efficacy, and safety of EB-RFA for MHO.We retrospectively compared the stent patency and survival among 79 consecutive patients with MHO who underwent bilateral uncovered SEMS placement without and with EB-RFA between April 2016 and January 2020.Fifty-one patients (64.6%) underwent SEMS placement alone (stent alone group), whereas 28 (35.4%) underwent SEMS placement after EB-RFA (RFA-stent group). All procedures were successful (100%). During follow-up, stent occlusion occurred in 59 patients (74.7%), of which 40 (78.4%) and 19 (67.9%) were in the stent alone and RFA-stent groups, respectively. There was no difference in stent patency (192 ± 39.2 days vs 140 ± 53.7 days, P = 0.41) and survival (311 ± 24.7 days vs 311 ± 46.9 days, P = 0.73) between the stent alone and RFA-stent groups. Multivariate cox analysis showed a hazard ratio (HR) of 2.892 (1.579-5.294, P = 0.001) for stent occlusion in patients who did not receive chemotherapy. EB-RFA had no significant effect on stent occlusion (HR, 1.150, 0.644-2.053, P = 0.636).SEMS placement after EB-RFA in MHO was not associated with improvement in the stent patency or patient survival. Further prospective randomized studies are necessary to establish the effectiveness of EB-RFA with stents in MHO.

Pancreatic surgery may result in changes in pancreatic volume and endocrine function. The effects of pancreatic resection for benign neoplasms on pancreatic volume and endocrine function have not been established yet. This study aimed to investigate the long-term results of different pancreatic surgeries for benign pancreatic neoplasms on pancreatic volume and endocrine function.The medical records of 30 patients who underwent pancreaticoduodenectomy (PD) and 30 patients who underwent left-sided pancreatectomy(LP) for benign pancreatic neoplasms between 2005 and 2012 were reviewed. The changes in pancreatic volume after pancreatic surgery were assessed using multi-detector row computed tomography volumetry. Endocrine pancreatic function was evaluated on the basis of fasting glucose level or oral glucose tolerance test result.The median follow-up duration was 91.3 months (interquartile range, 75.7-119.1 months). Reduction in pancreatic volume after surgery was more pronounced in patients who underwent PD than in those who underwent LP (median percentage of volume reduction, 23.8% vs 5.1%, p .001). Multivariable analysis of prognostic factors for endocrine insufficiency showed that PD to be significant factor. (HR 3.87, 95% CI 1.12-14.66, p = .037).The surgical methods for benign pancreatic neoplasms affect the reduction in pancreatic volume. Furthermore, the methods of pancreatic surgery were associated with the risk of endocrine insufficiency. Further studies with a large number of patients are warranted to evaluate the association between the degree of volume reduction and the development of endocrine insufficiency.

Purpose This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.Materials and Methods Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.Results The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).Conclusion AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

To identify reliable MRI features for differentiating autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to summarize their diagnostic accuracy.We conducted a systematic literature review and meta-analysis using PubMed, EMBASE, and the Cochrane Library to identify original articles published between January 2006 and July 2021. The pooled diagnostic accuracy, including the diagnostic odds ratios (DORs) with 95% confidence intervals (CIs) of the identified features, was calculated using a bivariate random effects model.Twelve studies were included, and 92 overlapping descriptors were subsumed under 16 MRI features. Ten features favoring AIP were diffuse enlargement (DOR, 75; 95% CI, 9-594), capsule-like rim (DOR, 52; 95% CI, 20-131), multiple main pancreatic duct (MPD) strictures (DOR, 47; 95% CI, 17-129), homogeneous delayed enhancement (DOR, 46; 95% CI, 21-104), low apparent diffusion coefficient value (DOR, 30), speckled enhancement (DOR, 30), multiple pancreatic masses (DOR, 29), tapered narrowing of MPD (DOR, 15), penetrating duct sign (DOR, 14), and delayed enhancement (DOR, 13). Six features favoring PDAC were target type enhancement (DOR, 41; 95% CI, 11-158), discrete pancreatic mass (DOR, 35; 95% CI, 15-80), upstream MPD dilatation (DOR, 13), peripancreatic fat infiltration (DOR, 10), upstream parenchymal atrophy (DOR, 5), and vascular involvement (DOR, 3).This study identified 16 informative MRI features to differentiate AIP from PDAC. Among them, diffuse enlargement, capsule-like rim, multiple MPD strictures, and homogeneous delayed enhancement favored AIP with the highest DORs, whereas discrete mass and target type enhancement favored PDAC.• The MRI features with the highest pooled diagnostic odds ratios (DORs) for autoimmune pancreatitis were diffuse enlargement of the pancreas (75), capsule-like rim (52), multiple strictures of the main pancreatic duct (47), and homogeneous delayed enhancement (46). • The MRI features with the highest pooled DORs for pancreatic ductal adenocarcinoma were target type enhancement (41) and discrete pancreatic mass (35).

Background Single-operator cholangioscopy (SOC) provides an accurate diagnosis of indeterminate pancreaticobiliary strictures. However, the procedure is expensive and can be performed using only limited accessories. Therefore, we devised a novel tube-assisted biopsy (TAB) technique and evaluated its feasibility, diagnostic yield, and safety for indeterminate pancreaticobiliary strictures. Methods The medical records of patients with indeterminate pancreaticobiliary strictures who underwent TAB between September 2018 and July 2019 were reviewed. We assessed the technical success rate, adverse event rate, sensitivity, specificity, and overall accuracy of TAB in differentiating malignant from benign lesions. Results TABs were performed in 16 patients: 12 had biliary strictures; four had pancreatic strictures. The technical success rate was 93.7 % (15/16), and the sensitivity, specificity, and overall accuracy of TAB were 87.5 %, 100 %, and 93.7 %, respectively. No serious adverse events occurred either during or after the procedure in any of the patients. Conclusions TAB has an acceptable accuracy for the diagnosis of indeterminate pancreaticobiliary strictures and may represent a useful diagnostic method in patients where SOC cannot be implemented.

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

Background and Aims Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using an anti-migrating tubular self-expandable metal stent (ATSEMS) is performed in high surgical risk patients with acute cholecystitis. The newly introduced lumen-apposing metal stent (LAMS) is expected to reduce the risk of tubular self-expandable metal stent–related adverse events such as stent migration, but no comparative studies have been carried out between LAMSs and ATSEMSs for EUS-GBD. Methods We reviewed the prospectively collected EUS-GBD database at Asan Medical Center and Bucheon Soonchunhyang hospital to analyze consecutive patients with acute cholecystitis who underwent EUS-GBD with LAMSs or ATSEMSs between January 2015 and December 2017. Technical success, clinical success, adverse events, and recurrence of cholecystitis were evaluated. Results A total of 71 patients (36 with LAMSs, 35 with ATSEMSs) were analyzed. The LAMS group had longer median procedure time (15.5 minutes) than the ATSEMS group (11 minutes; P = .017). The 2 groups did not show significant differences in terms of technical success (LAMS, 94% vs ATSEMS, 100%; P = .49), clinical success (94% vs 100%; P = .49), procedure-related adverse events (0% vs 2.9%; P = .99), and stent-related late adverse events (11.8% vs 5.8%; P = .43). During follow-up, the 2 groups had similar rates of cholecystitis recurrence at 6 months (LAMS, 3.4% vs ATSEMS, 3.1%, P = .99) and 12 months (8.3% vs 3.1%, P = .56). Conclusions In high surgical risk patients with acute cholecystitis, LAMSs and ATSEMSs for EUS-GBD showed similar rates of technical success, clinical success, procedure-related adverse events, stent-related late adverse events, and recurrence of cholecystitis.

Objectives Histopathologic characteristics of choledochal cysts and their clinical implications have not been previously comprehensively studied. Methods Smooth muscle distribution patterns and other histologic findings (inflammation, metaplasia, dysplasia, and heterotopia) in 233 surgically resected choledochal cysts were evaluated. Results Mean patient age was 23.3 ± 19.8 years, with male:female ratio of 0.3. Most cases were Todani type I (175 cases, 75.1%) or IVa (56 cases, 24.1%). Choledochal cysts with thin scattered/no muscle fiber (175 cases, 75.1%) were the predominant pattern and were associated with more frequent postoperative biliary stricture (P = .031), less frequent pyloric metaplasia (P = .016), and mucosal smooth muscle aggregates (P 20 years vs ≤20 years), suggesting that chronic irritation in association with developmental anomalies involves tumorigenesis from choledochal cysts. Conclusion Smooth muscle distribution pattern of choledochal cyst may predict postoperative complication, raising clinical implications of smooth muscle patterns in postoperative management of choledochal cysts.

BACKGROUND AND AIM Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) has been proposed for pancreatic duct obstruction after failure of endoscopic retrograde pancreatography. We evaluate the long-term outcomes of EUS-PD using a fully covered self-expandable metal stent (FCSEMS) for pancreaticojejunal anastomosis (PJA) strictures following Whipple procedures. METHODS Twenty-three patients with PJA strictures underwent EUS-PD according to the findings of EUS-guided pancreatogram and the passage of the guidewire through PJA stricture (complete vs partial stricture) after failure of endoscopic retrograde pancreatography. Technical and clinical success, adverse events (AEs), and long-term outcomes were assessed. RESULTS Technical and clinical success was achieved in all patients. The complete and partial strictures were 11 and 12, respectively. The direct transanastomotic and transmural plastic stenting in partial PJA stricture was successful in only three patients (13%). Therefore, 20 patients underwent EUS-guided transmural FCSEMS placement during the initial attempt. Early AEs, including abdominal pain (n = 3) and peripancreatic fluid collection (n = 1), occurred in four patients (17.4%). During the follow-up periods (median, 27.2 months; interquartile range [IQR], 18.7-40.6), five patients (21.7%) developed late AEs, including asymptomatic stent fracture at the gastric end (n = 3), asymptomatic stent migration (n = 1), and stent occlusion (n = 1). The total duration of stent placement was 27.2 months (IQR, 18.7-40.6), and the median number of stent revision was 2 (IQR, 1-2). CONCLUSIONS In terms of safety and efficacy, EUS-PD with an FCSEMS showed favorable success and acceptable AEs rate and durable long-term outcomes.

The guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMNs) recommend surgical resection of all main-duct (MD) and mixed-type IPMNs in surgically fit patients. We conducted this study to identify the rates of high-grade dysplasia (HGD) and invasive carcinoma according to the morphological features of the main pancreatic duct (MPD) in patients with MD and mixed IPMN.We performed a retrospective study of 259 patients with histologically proven MD and mixed-type IPMNs who underwent surgery at six academic institutions.The rate of HGD and invasive carcinoma was 11.1% (24/216) in patients without enhancing mural nodules (MNs) and 69.8% (30/43) in patients with MNs. Multivariate analysis showed that MPD diameter of ≥10 mm [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.155-5.505; P = 0.02], diffuse MPD dilatation (OR, 3.2; 95% CI, 1.152-8.998; P = 0.02), and presence of enhancing MNs in MPD (OR, 9.6; 95% CI, 3.928-23.833, P 0.0001) were significant predictors of HGD and invasive carcinoma. Of the 216 patients without enhancing MNs, 79 patients (36.6%) having both segmental MPD dilatation and MPD diameter of10 mm showed significantly lower rates of HGD and invasive carcinoma (3/79, 3.8%) than patients having both diffuse MPD dilatation and MPD diameter ≥10 mm (9/36, 25%, P = 0.001).MD and mixed-type IPMNs having segmental MPD dilatation with MPD dilation10 mm and no enhancing MNs on imaging showed a significantly lower rate of HGD and invasive carcinoma, and watchful follow-up instead of immediate surgical resection might be possible in these patients.

(E)-3,4-Dihydroxybenzylideneacetone (compound 1) inhibited receptor activator of NF-κB ligand-induced osteoclastogenesis of C57BL/6 bone marrow monocyte/macrophages with IC50 of 7.8 μM (IC50 of alendronate, 3.7 μM) while stimulating the differentiation of MC3T3-E1 osteoblastic cells, accompanied by the induction of Runt-related transcription factor 2, alkaline phosphatase, and osteocalcin. (E)-4-(3-Hydroxy-4-methoxyphenyl)-3-buten-2-one (compound 2c) showed a dramatically increased osteoclast-inhibitory potency with IC50 of 0.11 μM while sustaining osteoblast-stimulatory activity. (E)-4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one (compound 2g) stimulated alkaline phosphatase production 2-fold at 50 μM without changing osteoclast-inhibitory activity, compared with compound 1. Oral administration of compounds 1, 2c, and 2g prevented ovariectomy-induced osteoporosis in ddY mice to a degree proportional to their osteoclastogenesis-inhibitory potencies. The administration of 1 (mg/kg)/d compound 2c ameliorated histomorphometry of osteoporotic bone to a degree comparable with 10 (mg/kg)/d alendronate. Conclusively, the in vitro capacity of a few benzylideneacetone derivatives to inhibit osteoclastogenesis supported by independent osteoblastogenesis activation was convincingly reflected in in vivo management of osteoporosis, suggesting a potential novel therapeutics for osteopenic diseases.

Endoscopic gallbladder drainage (GBD) has been performed as an alternative to percutaneous drainage for acute cholecystitis. To date, there has been no comparative study between EUS-guided cholecystostomy (EUSC) and endoscopic transpapillary cholecystostomy (ETC). The aim of this study was to compare the outcomes of EUSC and ETC.A retrospective review of an endoscopic GBD database prospectively collected at the Asan Medical Center (between July 2010 and December 2014) was performed to identify consecutive patients with acute cholecystitis who underwent attempted endoscopic GBD. Procedural and long-term outcomes were evaluated using inverse probability of treatment weighting (IPTW).A total of 172 patients (76 in the EUSC group and 96 in the ETC group) were included in this study. Seven patients who failed to undergo ETC crossed over to the EUSC group. After adjustment with the IPTW method, technical success (99.3% vs 86.6%, P .01) and clinical success (99.3% vs 86%, P .01) rates were significantly higher in the EUSC group than in the ETC group. The procedure-related adverse event rate was significantly higher in the ETC group (7.1% vs 19.3%, P = .02). The cholecystitis or cholangitis recurrence rate (12.4% vs 3.2%) was also higher in the ETC group than in the EUSC group, as identified using Cox analysis (hazard ratio, 3.01; 95% confidence interval, .73-12.9; P = .04).In patients with acute cholecystitis who are unfit for surgery, EUSC may be a more suitable treatment method than ETC.

A two-stage procedure involving endoscopic retrograde cholangiopancreatography (ERCP), followed by cholecystectomy, is one of the primary treatments of concomitant gallstones and choledocholithiasis. However, negative findings on ERCP and migrating gallstones after cholecystectomy are major concerns. This study aimed to identify the prevalence of unnecessary ERCP and to develop and validate a predictive nomogram using preoperative factors in patients who underwent a two-stage procedure. Consecutive 931 patients were treated with the two-stage procedure for evident gallstones and suspected choledocholithiasis. After the cholecystectomy, a cholangiogram was performed to confirm the absence of the migrating gallstones. The patients were divided into derivation (n = 652) and validation (n = 279) cohorts. A total of 26.5% (247/931) patients had unnecessary ERCP (negative choledocholithiasis, 14.6%; migrating gallstones, 11.9%). No stones on images (P

Recently, laparoscopic distal pancreatectomy (LDP) has become the standard procedure for resection of left-sided pancreatic tumors. Fluid collection (FC) at the resection margin of the pancreatic stump after LDP is a frequent radiological finding. However, there have been few treatment guidelines and the optimal management for this clinical finding is unclear. The aim of present study is to define the incidence of FC and suggest the optimal management for FC after LDP. A total of 1227 patients who underwent LDP between March 2005 and December 2015 were collected. FC was considered present when the longest diameter of the lesion on CT scan was > 3 cm. A follow-up with at least two CT image was available for 1102 patients. Of these, 689 (62.5%) patients showed initial fluid collection (IFC) at the pancreas resection site in immediate postoperative CT. IFC (+) group had higher proportion of men, BMI, and higher rate of concomitant splenectomy than IFC (−) group. Among patients with FC after LDP, the treatment group had more frequent leukocytosis and accompanying symptoms than the observation group. Seventy-seven patients underwent therapeutic interventions for FC after LDP. Among them, 55 (71.4%) patients underwent endoscopic ultrasonography-guided gastrocystostomy (EUS-GC). EUS-GC group had a higher success rate (85.6 vs. 63.6%, p

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is increasingly accepted as an effective treatment option in patients who require drainage for acute cholecystitis. A newly designed lumen-apposing metal stent (LAMS) has been introduced recently in this procedure. In this study, we evaluated the feasibility and safety of the newly designed LAMS in patients with acute cholecystitis who were unsuitable for cholecystectomy. Between Mar 2017 and Oct 2017, 22 patients with acute cholecystitis who were unsuitable for cholecystectomy underwent EUS-GBD with the newly designed LAMS. We evaluated the technical and clinical success and the adverse event profiles. EUS-GBD with newly designed LAMS was technically and clinically successful in 21 of the 22 patients. EUS-GB stenting was performed at urgent setting in 17 patients, while 5 patients, who had undergone initial PTGBD, underwent EUS-GB stenting to remove PTGBD tube. The median procedure time was 11.5 (range 8.8–17.0) min. A late adverse event of stent occlusion developed in one patient. Stent migration was not observed during follow-up (median 318.0 days, range 39.0–398.0 days) and cumulative stent patency rate at 1 year was 95%. EUS-GBD with newly designed LAMS is feasible and shows acceptable safety profiles for both the urgent drainage of acute cholecystitis and elective internalization following PTGBD in patients with high surgical risk.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently used for the preoperative histologic diagnosis of pancreatic cancer. However, debate continues regarding the clinical merits of preoperative EUS-FNA for the management of resectable pancreatic cancer. We aimed to evaluate the benefits and safety of preoperative EUS-FNA for resectable distal pancreatic cancer. The medical records of 304 consecutive patients with suspected distal pancreatic cancer who underwent EUS-FNA were retrospectively reviewed to evaluate the clinical benefits of preoperative EUS-FNA. We also reviewed the medical records of 528 patients diagnosed with distal pancreatic cancer who underwent distal pancreatectomy with or without EUS-FNA. The recurrence rates and cancer-free survival periods of patients who did or did not undergo preoperative EUS-FNA were compared. The diagnostic accuracy of preoperative EUS-FNA was high (sensitivity, 87.5%; specificity, 100%; positive predictive value 100%; accuracy, 90.7%; negative predictive value, 73.8%). Among patients, 26.7% (79/304) avoided surgery based on the preoperative EUS-FNA findings. Of the 528 patients who underwent distal pancreatectomy, 193 patients received EUS-FNA and 335 did not. During follow-up (median 21.7 months), the recurrence rate was similar in the two groups (EUS-FNA, 72.7%; non-EUS-FNA, 75%; P = 0.58). The median cancer-free survival was also similar (P = 0.58); however, gastric wall recurrence was only encountered in the patients with EUS-FNA (n = 2). Preoperative EUS-FNA is not associated with increased risks of cancer-specific or overall survival. However, clinicians must consider the potential risks of needle tract seeding, and care should be taken when selecting patients.

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

Background Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been increasingly used for the management of various solid pancreatic tumors. This study aimed to evaluate the feasibility and safety of EUS-RFA for serous cystic neoplasms (SCNs). Methods 13 patients with microcystic SCNs with honeycomb appearance underwent EUS-RFA using a 19-gauge RFA needle. Before ablation, cystic fluid was aspirated until a thin layer of fluid remained. Results EUS-RFA was successful in all patients. Seven patients underwent a single session and the remaining six patients underwent a second session of EUS-RFA. One patient (7.7 %) experienced self-limited abdominal pain after EUS-RFA. During a median follow-up period of 9.21 months (interquartile range [IQR] 5.93 – 15.38), the median volume of the SCNs decreased from 37.82 mL (IQR 15.03 – 59.53) at baseline to 10.95 mL (IQR 4.79 – 32.39) at the end of follow-up. A radiologic partial response was achieved in eight patients (61.5 %). Conclusions EUS-RFA is technically feasible and showed an acceptable rate of adverse events for patients with SCNs. A long-term follow-up study is required to evaluate the efficacy of EUS-RFA.

Postoperative abdominal fluid collections (PAFCs) are a potentially fatal complication of pancreatobiliary surgery. Endoscopic ultrasound (EUS)-guided drainage has recently been shown to be effective in treating PAFCs of more than 4 weeks old. Little is currently known, however, regarding the EUS-guided drainage of PAFCs of less than 4 weeks. This study assessed the efficacy and safety of the early drainage (

Background The diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP. Methods A comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy. Results The meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70–80.75); sensitivity 0.64 (95% CI, 0.59–0.69); specificity 0.93 (95% CI, 0.91–0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla). Conclusions Current data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.

Background/Aims Presence of enhanced mural nodules, which can be visualized using computed tomography (CT), is one of high-risk stigmata in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). Conversely, the absence of enhanced mural nodules on preoperative imaging does not exclude malignant risk. The present study aimed to investigate other morphological features as predictors of malignancy in "pure" BD-IPMNs without enhanced mural nodules on CT. Methods This retrospective study included 180 patients with surgically confirmed "pure" BD-IPMNs of the pancreas and no enhanced mural nodules on preoperative CT. The study was conducted at 15 tertiary referral centers throughout South Korea. Univariate and multivariate analyses were used to identify significant predictors of malignancy. Results BD-IPMNs with low-grade (n=84) or moderate-grade (n=76) dysplasia were classified as benign; those with high-grade dysplasia (n=8) or invasive carcinoma (n=12) were classified as malignant. The multivariate analysis revealed that cyst size ≥30 mm (odds ratio, 8.6; p=0.001) and main pancreatic duct diameter ≥5 mm (odds ratio, 4.1; p=0.01) were independent risk factors for malignancy in "pure" BD-IPMNs without enhanced mural nodules on CT. Endoscopic ultrasound detected enhanced mural nodules (6/82) that had been missed on CT, and two IPMNs with enhanced mural nodules were malignant. Conclusions In patients with "pure" BD-IPMNs who have no enhanced mural nodules on CT, cyst size ≥30 mm and main pancreatic duct diameter ≥5 mm may be associated with malignancy.

Background Radiofrequency ablation (RFA) has been increasingly employed in experimental and clinical settings for the management of pancreatic lesions. This study aimed to assess the safety and efficacy of endoscopic ultrasound (EUS)-guided RFA for benign solid pancreatic tumors. Methods In a single-center, prospective study, 10 patients with benign solid pancreatic tumors underwent EUS-RFA. After the RFA electrode had been inserted into the pancreatic mass, the radiofrequency generator was activated to deliver 50 W of ablation power. Results Among the 10 patients, 16 sessions of EUS-RFA were successfully performed. Diagnoses included nonfunctioning neuroendocrine tumor (n = 7), solid pseudopapillary neoplasm (n = 2), and insulinoma (n = 1); the median largest diameter of the tumors was 20 mm (range 8 – 28 mm). During follow-up (median 13 months), radiologic complete response was achieved in seven patients. Two adverse events (12.4 %; 1 moderate and 1 mild) occurred. Conclusions EUS-RFA may be a safe and potentially effective treatment option in selected patients with benign solid pancreatic tumors. Multiple sessions may be required if there is a remnant tumor, and adverse events must be carefully monitored.

Type 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation of IgG4-related disease, shows a favorable prognosis in the short term. However, disease relapse is common in long-term follow-up, despite a successful initial treatment response. This study aimed to identify the predictors of relapse and long-term outcomes in patients with type 1 AIP. Patients with more than 2 years of follow-up who met the International Consensus Diagnostic Criteria for type 1 AIP were included. Patients who had undergone pancreatic operations associated with AIP or who lacked sufficient clinical data were excluded. All 138 patients achieved clinical remission with initial steroid therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24–197) months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within 3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of the proximal bile duct, was a significant independent predictor of relapse (hazard ratio 2.65; 95% confidence interval 1.44–4.89; p = 0.002), according to multivariate analysis. During the follow-up period, 16 (11.6%) patients experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de novo pancreatic calcifications/stones. No pancreatic cancer occurred in any patients. Type 1 AIP has common relapses, and patients with OOI, especially OOI of the proximal bile duct, appear to be at increased risk for relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic calcifications/stones, are common in patients with relapse. To reduce the relapse, longer maintenance treatment may be needed especially for patients at high risk for relapse.

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Since the publication of the Tokyo Guidelines in 2007 and their revision in 2013, appropriate management for acute cholecystitis has been more clearly established. Since the last revision, several manuscripts, especially for alternative endoscopic techniques, have been reported; therefore, additional evaluation and refinement of the 2013 Guidelines is required. We describe a standard drainage method for surgically high-risk patients with acute cholecystitis and the latest developed endoscopic gallbladder drainage techniques described in the updated Tokyo Guidelines 2018 (TG18). Our study confirmed that percutaneous transhepatic gallbladder drainage should be considered the first alternative to surgical intervention in surgically high-risk patients with acute cholecystitis. Also, endoscopic transpapillary gallbladder drainage or endoscopic ultrasound-guided gallbladder drainage can be considered in high-volume institutes by skilled endoscopists. In the endoscopic transpapillary approach, either endoscopic naso-gallbladder drainage or gallbladder stenting can be considered for gallbladder drainage. We also introduce special techniques and the latest outcomes of endoscopic ultrasound-guided gallbladder drainage studies. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Aims Xanthogranulomatous cholecystitis (XGC), an unusual histologic variant of chronic cholecystitis, is characterized by mixed foamy histiocytic and lymphoplasmocytic infiltration and fibrosis. Radiologically, the poorly defined nodular growth pattern often leads to the misinterpretation of XGC as gallbladder cancer. In this study, we aimed to identify the relationship of XGC with IgG4-related cholecystitis, Methods and Results We re-evaluated 57 surgically resected XGCs and 104 conventional chronic cholecystitis cases, according to the histologic features observed in IgG4-related disease, including lymphoplasmocytic infiltration, storiform fibrosis, obliterative phlebitis, and IgG4-positive plasma cells. XGCs contained a significantly increased mean number of IgG4-positive plasma cells (34.8/high-power field [HPF]), compared with conventional chronic cholecystitis (4.8/HPF; P 50 IgG4-positive cells per HPF. Nine XGCs (16%), including one case with IgG4-related autoimmune pancreatitis, exhibited “the histological features suggestive of IgG4-related disease”, as described in the consensus statement regarding this condition. Extracholecystic inflammatory extension (7 cases, P = .009) and mass-forming lesions (8 cases, P < .001) were more frequently seen in XGC cases with histological features suggestive of IgG4-related disease than in cases without those microscopic changes. Conclusions XGCs with IgG4-positive cell infiltration are considered mimickers, as xanthogranulomatous inflammation generally contradicts a diagnosis of IgG4-related disease and is weakly associated with other typical organ manifestations of IgG4-related disease. However, XGC may be a concurrent condition, particularly in patients with IgG4-related disease in other organs. This article is protected by copyright. All rights reserved.

Background We aimed to comprehensively evaluate the prognostic value of inflammation-based prognostic scores, including the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), exclusively in patients with advanced intrahepatic cholangiocarcinoma (iCCA). Methods Between May 2010 and April 2015, 305 patients with histologically documented unresectable or metastatic iCCA were treated with first-line gemcitabine plus cisplatin (GemCis). Among these, 257 patients had complete data for inflammation-based prognostic scores and were included. Results Median age was 59 (range: 27–78) years, and 158 patients (61.5%) were males. High mGPS was independently associated with poor progression-free survival (PFS; mGPS ≥1 vs. 0: median, 3.9 vs. 5.5 months; P = 0.001) and overall survival (OS; mGPS ≥1 vs. 0; median, 6.9 vs. 14.1 months; P = 0.002) in the multivariate analysis. Regarding high NLR (> median) and PLR (> median), although a potential association existed with poor PFS or OS in the univariate analysis, these did not remain as significant in the multivariate analyses. Conclusion The current study suggests that mGPS might be the relevant prognostic index that could stratify the survival outcomes of patients with unresectable or metastatic iCCA who received first-line GemCis.

The Tokyo Guidelines 2013 (TG13) include new topics in the biliary drainage section. From these topics, we describe the indications and new techniques of biliary drainage for acute cholangitis with videos. Recently, many novel studies and case series have been published across the world, thus TG13 need to be updated regarding the indications and selection of biliary drainage based on published data. Herein, we describe the latest updated TG13 on biliary drainage in acute cholangitis with meta-analysis. The present study showed that endoscopic transpapillary biliary drainage regardless of the use of nasobiliary drainage or biliary stenting, should be selected as the first-line therapy for acute cholangitis. In acute cholangitis, endoscopic sphincterotomy (EST) is not routinely required for biliary drainage alone because of the concern of post-EST bleeding. In case of concomitant bile duct stones, stone removal following EST at a single session may be considered in patients with mild or moderate acute cholangitis except in patients under anticoagulant therapy or with coagulopathy. We recommend the removal of difficult stones at two sessions after drainage in patients with a large stone or multiple stones. In patients with potential coagulopathy, endoscopic papillary dilation can be a better technique than EST for stone removal. Presently, balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is used as the first-line therapy for biliary drainage in patients with surgically altered anatomy where BE-ERCP expertise is present. However, the technical success rate is not always high. Thus, several studies have revealed that endoscopic ultrasonography-guided biliary drainage (EUS-BD) can be one of the second-line therapies in failed BE-ERCP as an alternative to percutaneous transhepatic biliary drainage where EUS-BD expertise is present.

OBJECTIVES This study aims to identify the computed tomography (CT) features that may differentiate nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) with lymph node (LN) metastasis from NF-PanNETs without lymph node metastasis. METHODS We retrospectively analyzed 166 NF-PanNETs in 166 patients who had undergone surgical resection (median age, 53). Two radiologists evaluated the qualitative and quantitative CT findings. Through univariate and multivariate logistic regression analyses, we determined independent significant findings for differentiating NF-PanNETs with LN metastasis from NF-PanNETs without LN metastasis. Recurrence-free survival (RFS) and overall survival (OS) were compared between the 2 groups using Kaplan-Meier analysis and log-rank testing. RESULTS Of the 166 NF-PanNETs, 24 (14.5%) tumors demonstrated LN metastasis. Three CT findings, radiologic LN enlargement (adjusted odds ratio [OR], 11.76; P = 0.001), liver metastasis (OR, 10.31; P = 0.027), and portal enhancement ratio of

Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.

Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P

Background and study aims The aim of this study was to investigate the long-term outcomes after endoscopic ultrasound (EUS)-guided pancreatic cyst ablation. Patients and methods In a single-center, prospective study, 164 patients with pancreatic cysts underwent EUS-guided cyst ablation using ethanol with paclitaxel. The inclusion criteria were as follows: unilocular or oligolocular cysts; clinically indeterminate cysts that required EUS fine-needle aspiration; and/or cysts that grew during the observation period. Treatment response was classified as complete resolution, partial resolution, or persistent cyst, with Results The median largest diameter of the cyst was 32 mm and the median volume was 17.1 mL. Based on cyst fluid analysis there were 71 mucinous cystic neoplasms, 16 serous cystic neoplasms, 11 intraductal papillary mucinous neoplasms, 3 pseudocysts, and 63 indeterminate cysts. Sixteen treated patients (9.8 %) had adverse events (1 severe, 4 moderate, and 11 mild). Treatment response was as follows: complete resolution in 114 (72.2 %), partial resolution in 31 (19.6 %), and persistent cysts in 13 (8.2 %). Twelve of the 13 patients with persistent cysts underwent surgery. During clinical and imaging follow-up (median 72 months, interquartile range 50 – 85 months) of the 114 patients with complete resolution, only two patients (1.7 %) showed cyst recurrence. Based on multivariate analysis, the absence of septa (odds ratio [OR] 7.12, 95 % confidence interval [CI] 2.72 – 18.67) and cyst size less than 35 mm (OR 2.39, 95 %CI 1.11 – 5.16) predicted complete resolution. Conclusion Among patients with pancreatic cysts in whom complete resolution was achieved after EUS-guided cyst ablation, 98.3 % remained in remission at 6-year follow-up. Unilocular form and small cyst size were predictive of complete resolution. This treatment approach may be an effective and durable alternative to surgery.Trial registered at ClinicalTrials.gov (NCT 00689715).

Borderline resectable pancreatic cancer (BRPC) is a potentially resectable disease but is associated with poorer survival compared to primary resectable disease. There has been no prospective trial that compare the efficacy of FOLFIRNOX and gemcitabine-based regimen for BRPC. Between February 2013 and December 2014, 18 patients with BRPC receiving FOLFIRINOX were reviewed retrospectively. For comparative analysis, data for all BRPC patients (n=18) in our previous phase 2 study of neoadjuvant fixed-dose rate-gemcitabine plus capecitabine were pooled. Patients received a median 6 cycles (range, 3-13) of FOLFIRINOX. Surgical resection was performed in 12 patients (67%) and R0 resection in 9 patients. Median progression-free survival (PFS) and overall survival (OS) were 16.8 (95% confidence interval [CI], 9.4-24.2) and 21.2 (95% CI, 14.2-28.2) months, respectively. Patients who underwent surgical resection showed significantly better PFS (p=0.01) and OS (p=0.003) than those unresected. In the exploratory analysis, patients receiving FOLFIRINOX showed significantly longer PFS compared to those receiving fixed-dose rate-gemcitabine plus capecitabine (median 16.8 months [95% CI, 9.4-24.2] vs. 6.5 months [1.6-11.3]; p = 0.04). There was a trend toward improved OS in patients who received FOLFIRINOX (median 21.2 months [95% CI, 14.2-28.2]) compared to those who received fixed-dose rate-gemcitabine plus capecitabine (13.6 months [11.8-15.4]; p=0.12). FOLFIRINOX was feasible and effective as neoadjuvant chemotherapy for patients with BRPC and may have improved efficacy compared to a gemcitabine-based regimen.

Background and Aims Although fully covered self-expandable metal stents (FCSEMSs) have been commonly used for EUS-guided biliary drainage (EUS-BD), FCSEMS migration is a main limitation of this procedure. In the present study we evaluated the technical and clinical success rates, adverse events, and long-term outcomes of a newly developed hybrid stent that has been customized for EUS-BD. Methods From September 2011 to May 2015, 54 consecutive patients with biliary obstruction were enrolled in this prospective, observational study. These patients were candidates for alternative BD techniques because of failed ERCP. The hybrid metal stent used for EUS-BD in this study was partially covered, had anchoring flaps, and is commercially available in Korea. Results EUS-guided hepaticogastrostomy (EUS-HGS) was performed in 21 patients and EUS-guided choledochoduodenostomy (EUS-CDS) in 33 patients. The technical and clinical success rates of EUS-BD were 100% (54/54) and 94.4% (51/54), respectively. Immediate adverse events developed after EUS-BD in 9 patients (16.6%; cholangitis in 3, bleeding in 2, self-limited pneumoperitoneum in 3, and abdominal pain in 1). Proximal or distal stent migration was not observed during the follow-up period (median, 148.5 days; IQR, 79.7-244), and the mean stent patency duration was 166.3 days and 329.1 days in the EUS-HGS and EUS-CDS groups, respectively. Conclusions EUS-BD with the hybrid metal stent is technically feasible and can effectively treat biliary obstruction after failed ERCP. EUS-BD with the hybrid metal stent can reduce stent-related adverse events, especially stent migration.

Background and study aim Percutaneous transhepatic biliary drainage (PTBD) is a rescue procedure after a failed endoscopic retrograde cholangiopancreatography. As PTBD causes patient discomfort, conversion of the PTBD to internal biliary stenting (PTBDS) may be required; however, PTBDS is sometimes difficult because of the tight stricture. We evaluated the efficacy and safety of conversion of external PTBD to endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) after failed PTBDS. Patients and methods A total of 16 patients with malignant distal biliary obstruction who underwent conversion of external PTBD to EUS-HGS after failed PTBDS were enrolled from two institutions in Korea and Japan. Data were analyzed retrospectively. Results The technical and clinical success rates were 100 % and 81 %, respectively. Early adverse events developed in two patients: proximal stent migration (n = 1), and cholecystitis (n = 1). Stents were occluded or migrated distally in five patients. The mean duration of stent patency was 402 days. Conclusions Conversion of external PTBD to EUS-HGS may be a good rescue option after failed PTBDS.

BACKGROUND: Bile duct injury (BDI) during laparoscopic cholecystectomy remains a serious iatrogenic surgical complication. BDI most often occurs as a result of misidentification of the anatomy; however, clinical evidence on its precise mechanism and surgeons' perceptions is scarce.METHODS: Surgeons from Japan, Korea, Taiwan, and the U.S., etc. (n = 614) participated in a questionnaire regarding their BDI experience and near-misses; and perceptions on landmarks, intraoperative findings, and surgical techniques. Respondents voted for a Delphi process and graded each item on a five-point scale. The consensus was built when ≥80% of overall responses were 4 or 5.RESULTS: Response rates for the first- and the second-round Delphi were 60.6% and 74.9%, respectively. Misidentification of local anatomy accounted for 76.2% of BDI. Final consensus was reached on: 1) Effective retraction of the gallbladder, 2) Always obtaining critical view of safety, and 3) Avoiding excessive use of electrocautery/clipping as vital procedures; and 4) Calot's triangle area and 5) Critical view of safety as important landmarks. For 6) Impacted gallstone and 7) Severe fibrosis/scarring in Calot's triangle, bail-out procedures may be indicated.CONCLUSIONS: A consensus was reached among expert surgeons on relevant landmarks and intraoperative findings and appropriate surgical techniques to avoid BDI. This article is protected by copyright. All rights reserved.

Background and aims Acute necrotizing pancreatitis (ANP) can affect main pancreatic duct (MPD) as well as parenchyma. However, the incidence and outcomes of MPD disruption has not been well studied in the setting of ANP. Methods This retrospective study investigated 84 of 465 patients with ANP who underwent magnetic resonance cholangiopancreatography and/or endoscopic retrograde cholangiopancreatography. The MPD disruption group was subclassified into complete and partial disruption. Results MPD disruption was documented in 38% (32/84) of the ANP patients. Extensive necrosis, enlarging/refractory pancreatic fluid collections (PFCs), persistence of amylase-rich output from percutaneous drainage, and amylase-rich ascites/pleural effusion were more frequently associated with MPD disruption. Hospital stay was prolonged (mean 55 vs. 29 days) and recurrence of PFCs (41% vs. 14%) was more frequent in the MPD disruption group, although mortality did not differ between ANP patients with and without MPD disruption. Subgroup analysis between complete disruption (n = 14) and partial disruption (n = 18) revealed a more frequent association of extensive necrosis and full-thickness glandular necrosis with complete disruption. The success rate of endoscopic transpapillary pancreatic stenting across the stricture site was lower in complete disruption (20% vs. 92%). Patients with complete MPD disruption also showed a high rate of PFC recurrence (71% vs. 17%) and required surgery more often (43% vs. 6%). Conclusions MPD disruption is not uncommon in patients with ANP with clinical suspicion on ductal disruption. Associated MPD disruption may influence morbidity, but not mortality of patients with ANP. Complete MPD disruption is often treated by surgery, whereas partial MPD disruption can be managed successfully with endoscopic transpapillary stenting and/or transmural drainage. Further prospective studies are needed to study these items.

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

Background/Aims: Interventional endoscopists may utilize contrast-enhanced harmonic endoscopic ultrasound (CEHEUS) for image guidance during radiofrequency ablation (RFA) because of its capability to delineate real-time tumor perfusion dynamics. The purpose of this study was to assess the utility of CEH-EUS for the guidance and monitoring of endoscopic RFA. Methods: Nineteen consecutive patients with solid abdominal tumors who underwent CEH-EUS and endoscopic RFA were included. The extent of the ablation was assessed by CEH-EUS at 5 to 7 days after RFA. Additional RFAs were performed under CEH-EUS guidance. Results: The diagnoses were as follows: nonfunctioning neuroendocrine tumor (n=13), solid pseudopapillary neoplasm (SPN) (n=2), insulinoma (n=1), left adrenal adenoma (n=2), and left adrenal oligometastasis (n=1). Pre-CEH-EUS findings revealed that 17 cases showed hyperenhanced patterns and two cases of SPN showed isoenhanced patterns. CEH-EUS-assisted RFA was technically feasible in all 19 patients. After the first RFA session, seven patients of the treated tumors showed the disappearance of intratumoral enhancement on CEH-EUS, whereas 12 showed residual contrast enhancement. Twelve patients with incomplete ablation were further treated with additional RFA under real-time CEH-EUS guidance. Radiologic complete response was observed in 13 patients (68.4%). Among the 35 ablation procedures, the only adverse events were two episodes of pancreatitis (5.7%; 1 moderate and 1 mild). During the median follow-up of 28 months, the local recurrence rate was 7.7%. Conclusions: The application of CEH-EUS for RFA could be helpful in assessing early treatment response after ablation and targeting residual viable tumors during additional ablation sessions. (Gut Liver 2020;14:826-832)

PURPOSE Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM. Materials and Methods Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors. RESULTS Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy. CONCLUSION 2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.

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

Recent research has shown that a substantial number of patients with primary sclerosing cholangitis (PSC) can also have elevated serum/tissue IgG4. The aim of our study was to develop a simple scoring system for the discrimination of IgG4-related sclerosing cholangits (IgG4-SC) from PSC. Patients with IgG4-SC (n = 39) and PSC (n = 76) who had intrahepatic/hilar strictures were included. Candidate-differentiating variables included patient age, other organ involvement (OOI), inflammatory bowel disease, serum IgG4, and cholangiographic features. A scoring system was developed on the basis of these variables, and its performance was internally validated using a bootstrapping-based method. The scoring system in the final model included age (

Background and Aims Radiofrequency ablation (RFA) has been used as a valuable treatment modality for various unresectable malignancies. EUS-guided radiofrequency ablation (EUS-RFA) of the porcine pancreas was reported to be feasible and safe in our previous study, suggesting that EUS-RFA may be applicable as an adjunct and effective alternative treatment method for unresectable pancreatic cancer. This study aimed to assess the technical feasibility and safety of EUS-RFA for unresectable pancreatic cancer. Methods An 18-gauge endoscopic RFA electrode and a radiofrequency generator were used for the procedure. The length of the exposed tip of the RFA electrode was 10 mm. After insertion of the RFA electrode into the mass, the radiofrequency generator was activated to deliver 20 to 50 W ablation power for 10 seconds. Depending on tumor size, the procedure was repeated to sufficiently cover the tumor. Results EUS-RFA was performed successfully in all 6 patients (median age 62 years, range 43-73 years). Pancreatic cancer was located in the head (n = 4) or body (n = 2) of the pancreas. The median diameter of masses was 3.8 cm (range 3cm-9cm). Four patients had stage 3 disease, and 2 patients had stage 4 disease. After the procedure, 2 patients experienced mild abdominal pain, but there were no other adverse events such as pancreatitis or bleeding. Conclusions EUS-RFA could be a technically feasible and safe option for patients with unresectable pancreatic cancer.