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Background/Aims Endoscopic ultrasonography (EUS) provides high-resolution images and is superior to computed tomography (CT) scan in diagnosing small pancreatic ductal adenocarcinoma (PDAC). As a result, the use of EUS for early detection of PDAC has attracted attention. This study aimed to identify the clinical and radiological characteristics of patients with PDAC diagnosed by EUS but not found on CT scan. Methods The medical records of patients diagnosed with PDAC at 12 tertiary referral centers in Korea from January 2003 to April 2019 were reviewed. This study included patients with pancreatic masses not clearly observed on CT scan but identified on EUS. The clinical characteristics and radiological features of the patients were analyzed, and survival analysis was performed. Results A total of 83 patients were enrolled. The most common abnormal CT findings other than a definite mass was pancreatic duct dilatation, which was identified in 61 patients (73.5%). All but four patients underwent surgery. The final pathologic stages were as follows: IA (n=31, 39.2%), IB (n=8, 10.1%), IIA (n=20, 25.3%), IIB (n=17, 21.5%), III (n=2, 2.5%), and IV (n=1, 1.4%). The 5-year survival rate of these patients was 50.6% (95% confidence interval, 38.8% to 66.7%). Elevated liver function testing and R1 resection emerged as significant predictors of mortality in the multivariable Cox regression analysis. Conclusions This multicenter study demonstrated favorable long-term prognosis in patients with PDAC diagnosed by EUS but indeterminate on CT scan. EUS should be considered for patients with suspected PDAC but indeterminate on CT scan.

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.

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.

We aimed to assess the ability of CT-determined resectability, as defined by a recent version of NCCN criteria, and associated CT findings to predict margin-negative (R0) resection in patients with PDAC after neoadjuvant FOLFIRINOX chemotherapy. Sixty-four patients (36 men and 28 women; mean age, 58.8 years) with borderline resectable or unresectable PDAC who received neoadjuvant FOLFIRINOX were evaluated retrospectively. CT findings were independently assessed by two abdominal radiologists according to NCCN criteria (version 3. 2019). Tumor resectability was classified as resectable, borderline resectable, or unresectable, and change in resectability was classified as regression, stability, or progression. The associations of R0 resection rate with CT-determined resectability and change in resectability categories were evaluated, as were the sensitivity and specificity of NCCN criteria for R0 resection. Factors associated with R0 resection were identified by logistic regression analysis. R0 resection rate did not differ significantly among the resectable, borderline resectable, or unresectable PDAC (67–73%, p = 0.95) or among PDAC with regression, stability, or progression (56–77%, p = 0.39). The sensitivity and specificity for R0 resection were 67% and 37%, respectively, for resectability (resectable/borderline vs. unresectable) and 80% and 21%, respectively, for changes in resectability (regression/stable vs. progression). Low-contrast enhancement of soft tissue contacting artery (≤ 46.4 HU) was independently associated with R0 resection (p = 0.01). CT-determined resectability after neoadjuvant FOLFIRINOX chemotherapy was relatively insensitive and non-specific for predicting R0 resection. Low-contrast enhancement of soft tissue contacting artery may increase the ability of CT to predict R0 resection. • Margin-negative resection rate of pancreatic cancer following FOLFIRINOX therapy did not differ among each resectability (67–73%, p = 0.95) based on NCCN criteria or changes in resectability categories (56–77%, p = 0.39). • The sensitivity and specificity for margin-negative resection were 67% and 37% for resectability (resectable/borderline vs. unresectable) and 80% and 21% for changes in resectability (regression/stable vs. progression). • Low-contrast enhancement of soft tissue contacting artery (≤ 46.4 HU) was independently associated with margin-negative resection (p = 0.01).

The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks, FBG cream significantly reduced the appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with a control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced from 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.

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.

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.

Background and Objectives: Ethanol retention therapy (ERT) under EUS guidance or a percutaneous approach is a safe treatment for large symptomatic hepatic cysts. However, reports on the long-term outcomes after ERT are very rare. Therefore, we aimed to evaluate the long-term outcomes of ERT in symptomatic large hepatic cysts. Materials and Methods: A total of 47 consecutive patients with large symptomatic hepatic cysts treated at the Asan Medical Center from April 2009 to October 2017 were analyzed. Thirty patients with right hepatic cysts were treated with ERT through a percutaneous approach, and 14 patients with left hepatic cysts were treated with ERT under EUS guidance. Three patients were treated with ERT using both methods. Results: Of the 47 patients, 43 (91%) showed complete regression and four (9%) showed partial regression on abdominal computed tomography. Recurrence of the cysts was not observed during the follow-up surveillance of a median of 66 months. Conclusions: Percutaneous catheter drainage-guided ERT and EUS-guided ERT, based on their favorable long-term outcomes, may be considered as first-line treatments in patients with large symptomatic hepatic cysts.

Background Peroral cholangioscopy (POCS) can be useful for difficult bile duct stone clearance. Large prospective multinational data on POCS-guided lithotripsy for clearing difficult bile duct stones in a single session of endoscopic retrograde cholangiopancreatography (ERCP) are missing. Methods Patients with difficult bile duct stones (defined as one or more of: largest stone diameter ≥ 15 mm, failed prior attempt at stone clearance, impacted, multiple, hepatic duct location, or located above a stricture) were enrolled at 17 centers in 10 countries. The principal endpoint was stone clearance in a single ERCP procedure using POCS. Results 156 patients underwent 174 sessions of POCS-guided electrohydraulic or laser lithotripsy. Stone clearance had failed in a previous ERCP using traditional techniques in 124/156 patients (80 %), while 32 /156 patients (21 %) were referred directly to POCS-guided therapy based on preprocedural assessment of the difficulty of stone clearance. In 101/156 patients (65 %), there were impacted stones. POCS-guided stone clearance was achieved in a single POCS procedure in 125 /156 patients (80 %, 95 % confidence interval [CI] 73 % – 86 %), and was significantly more likely for stones ≤ 30 mm compared with > 30 mm (odds ratio 7.9, 95 %CI 2.4 – 26.2; P = 0.002). Serious adverse events occurred in 3/156 patients (1.9 %, 95 %CI 0.4 % – 5.5 %), and included pancreatitis, perforation due to laser lithotripsy, and cholangitis (n = 1 each), all resolved within 1 week. Conclusion POCS-guided lithotripsy is highly effective for clearance of difficult bile duct stones in a single procedure and successfully salvages most prior treatment failures. It may also be considered first-line therapy for patients with difficult choledocholithiasis to avoid serial procedures.

Various core biopsy needles have previously been developed for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). However, the properties of needle gauge in the diagnostic outcomes of solid pancreatic lesions remain unknown. This trial compared the procurement rates of histologic cores from solid pancreatic lesions with EUS-FNB using 20- and 25-gauge (G) FNB needles. In a prospective randomized multicenter clinical trial, patients with solid pancreatic lesions underwent EUS-FNB with either a 20-gauge or a 25-gauge FNB needle. The rates of histologic core procurement, overall diagnostic accuracy, and adverse events were compared between the two groups (20-gauge or 25-gauge FNB needle). In total, 88 patients (48 men, 40 women, mean age 65.7 years) were enrolled. No significant differences were found in the demographic characteristics between the two groups (20-gauge or 25-gauge FNB needle). The procurement rate of histologic cores in the 20-guage FNB needle group (41/45, 91.1%) was significantly higher than that in the 25-guage FNB needle group (32/43, 74.4%, P = 0.037). However, no significant differences were found in the overall diagnostic accuracy between 20-guage FNB needle (40/45, 88.9%) and 25-guage FNB needle (34/43, 79.1%, P = 0.208). No procedure-related adverse events were observed in either group. Although both FNB needles provided high overall diagnostic accuracy, the reliability of the 20-guage FNB needle is better than the 25-guage FNB needle when retrieving samples for histological analysis.

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. (Gut Liver 2019;13:461-470)

Triclosan (TCS) is an antimicrobial compound used in consumer products. The purpose of current study was to examine toxicology and risk assessment of TCS based on available data. Acute toxicities of oral, transdermal and inhalation routes were low, and phototoxicity and neurotoxicity were not observed. Topical treatment of TCS to animal caused mild irritation. TCS did not induce reproductive and developmental toxicity in rodents. In addition, genotoxicity was not considered based on in vitro and in vivo tests of TCS. It is not classified as a carcinogen in international authorities such as International Agency for Research on Cancer (IARC). No-observed-adverse-effect level (NOAEL) was determined 12 mg/kg bw/day for TCS, based on haematoxicity and reduction of absolute and relative spleen weights in a 104-week oral toxicity study in rats. Percutaneous absorption rate was set as 14%, which was human skin absorption study reported by National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (2009). The systemic exposure dosage (SED) of TCS has been derived by two scenarios depending on the cosmetics usage of Koreans. The first scenario is the combined use of representative cosmetics and oral care products. The second scenario is the combined use of rinse-off products of cleansing, deodorants, coloring products, and oral care products. SEDs have been calculated as 0.14337 mg/kg bw/day for the first scenario and 0.04733 mg/kg bw/day for the second scenario. As a result, margin of safety (MOS) for the first and second scenarios was estimated to 84 and 253.5, respectively. Based on these results, exposure of TCS contained in rinse-off products, deodorants, and coloring products would not pose a significant health risk when it is used up to 0.3%.

Background and Objectives: EUS-guided biliary drainage (EUS-BD) is increasingly utilized to manage unresectable malignant biliary obstruction after a failed ERCP. However, there is no data on how endoscopists perceive EUS-BD. The aim of this study was to investigate the perception of endoscopists on EUS-BD. Patients and Methods: A survey questionnaire of six topics with 22 survey statements was developed. A total of 17 pancreatobiliary endoscopists (10 from East and 7 from West) were invited to survey. The participants were asked to answer the multiple choice questionnaire and give comments. The opinions of the participants for individual survey statements were assessed using 5-point Likert scale. Results: All participants completed the survey. The endoscopists had a trend to perceive EUS-BD as a procedure indicated after a failed ERCP. Various EUS-BD methods were regarded as having different efficacy and safety. The superiority of EUS-BD over percutaneous transhepatic BD (PTBD) with regard to efficacy, procedure-related adverse events, and unscheduled re-intervention was not in agreement. Conclusions: EUS-BD was not yet perceived as the initial procedure to relieve the unresectable malignant biliary obstruction. Various EUS-BD methods were regarded as having different efficacy and safety. The superiority of EUS-BD over PTBD was not in agreement. Refining the procedure, developing dedicated devices, and gaining expertise in the procedure are necessary to popularize EUS-BD.

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

Background and Objectives: Rapid on-site cytologic evaluation (ROSE) increases the diagnostic yield of EUS-FNA. However, ROSE requires the presence of a cytopathologist and additional cost and time for slide staining and interpretation. Macroscopic on-site examination (MOSE) was recently introduced as an alternative to ROSE and showed high accuracy for the use in pathologic diagnosis. We evaluated the efficacy of MOSE in terms of tissue acquisition and diagnostic accuracy for abdominal lesions. Methods: We analyzed consecutive patients included who underwent EUS-guided fine needle biopsy (FNB) between January 2019 and November 2019. All procedures were done by dry suction using a 22G needle. Obtained specimens were expelled onto filter papers and evaluated by MOSE. Needle pass was done until the acquisition of satisfactory whitish macroscopic visible core or bloody tissue granules. The primary outcomes were successful tissue acquisition and accuracy for pathologic diagnosis. Results: In 75 patients (male, 52%; median age: 62 years), the pancreas was the most commonly targeted organ (81.4%) and the median target diameter was 25 mm. The median number of needle passes was 2.0 (range, 2–5). Successful targeting of the lesion was achieved in 75 patients (100%) and overall accuracy was 97.3%. There were no procedure-related adverse events. Conclusions: MOSE was effective for complementing EUS-FNB by ensuring the adequate acquisition of biopsy specimens with a minimal number of needle passes while providing a critically high diagnostic accuracy. MOSE seems to be a viable alternative to ROSE in select clinical situations.

Background: Endoscopic ultrasound-guided ablation (EUS-A) therapy is a minimally invasive procedure for pancreatic-cystic tumors in patients with preoperative comorbidities or in patients who are not indicated for surgical resection. However, histopathologic characteristics of pancreatic cysts after ablation have not been well-elucidated. Methods: Here, we analyzed pathological findings of 12 surgically resected pancreatic cysts after EUS-A with ethanol and/or paclitaxel injection. Results: Mean patient age was 49.8 ± 13.6 years with a 0.3 male/female ratio. Clinical impression before EUS-A was predominantly mucinous cystic neoplasms. Mean cyst size before and after ablation therapy was similar (3.7 ± 1.0 cm vs. 3.4 ± 1.6 cm; p = 0.139). Median duration from EUS-A to surgical resection was 18 (range, 1–59) months. Mean percentage of the residual neoplastic lining epithelial cells were 23.1 ± 37.0%. Of the resected cysts, 8 cases (67%) showed no/minimal (Conclusion: Above all, diffuse egg shell-like calcification along the pancreatic cystic walls with residual lining epithelia and/or ovarian-type stroma were characteristics of pancreatic cysts after EUS-A. Therefore, understanding these histologic features will be helpful for precise pathological diagnosis of pancreatic cystic tumor after EUS-A, even without knowing the patient’s history of EUS-A.

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia—a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.

Background. Radiofrequency ablation (RFA) is a palliative method known for its application in the endoscopic treatment of malignant bile duct obstruction. It may be a useful rescue method for metal stent malfunction caused by tumor ingrowth. This study aimed to examine the feasibility and safety of endoluminal RFA for occluded bilateral hilar metal stents due to tumor ingrowth in patients with malignant hilar bile duct obstruction. Methods: From March 2016 to June 2018, 11 patients with unresectable malignant hilar bile duct stricture with occluded bilateral hilar metal stents due to tumor ingrowth were enrolled. Endoluminal RFA was performed through a novel temperature-controlled catheter at a setting of 7 W power for 120 s with a target temperature of 80 °C via endoscopic retrograde cholangiopancreatography (ERCP). The patients’ demographics, clinical outcomes, and adverse events were investigated. Results: The median age was 64 (interquartile range, 54–72) years. All RFA procedures were successful. Clinical success was achieved in eight patients (72.7%). During the follow-up, eight patients (72.7%) showed stent dysfunction, and the median patency after RFA was 50 days (95% confidence interval (CI): 34–not available (NA)). All stent dysfunctions were successfully managed with ERCP. Ten patients died, and the median overall survival was 289 days (95% CI, 107–NA) from RFA to death. There was one case of mild abdominal pain after the procedure without serious adverse events. Conclusions: As a rescue therapy for occluded bilateral hilar metal stents due to tumor ingrowth, endoluminal RFA seemed to be safe and useful in selected patients.

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.

Radiofrequency ablation (RFA) is a well-established ablative procedure that causes coagulative necrosis of tumors, leading to local destruction of many solid-organ malignancies. RFA also has been known as a palliative method for the endoscopic treatment of malignant bile duct obstruction. Novel RFA catheters have opened the possibility of new endoscopic treatments and have been successfully used in endoscopic approaches for palliative intraductal ablation in patients with malignant bile duct obstruction. In this chapter, we reviewed the detailed methods and outcomes of endobiliary RFA.

The Asian Federation of Societies for Ultrasound in Medicine and Biology aimed to provide information on techniques and indications for contrast-enhanced harmonic endoscopic ultrasound (CH-EUS), and to create statements including the level of recommendation. These statements are based on current scientific evidence reviewed by a Consensus Panel of 15 internationally renowned experts. The reliability of clinical questions was measured by agreement rates after voting. Six statements were made on techniques, including suitable contrast agents for CH-EUS, differences between contrast agents, setting of mechanical index, dual imaging and duration and phases for observation. Thirteen statements were made on indications, including pancreatic solid masses, pancreatic cancer staging, pancreatic cystic lesions and mural nodules, detection of subtle pancreatic lesions, gallbladder sludge and polyps, hepatic lesions, lymph nodes, subepithelial lesions, visceral vascular diseases, guidance of fine needle aspiration and evaluation for local therapy. These international expert consensus guidelines will assist endosonographers in conducting CH-EUS according to evidence-based information.

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.

Background: Despite the scarcity of data based on randomized trials, FOLFIRINOX is widely used in the management of borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). We investigated the clinical outcomes of neoadjuvant FOLFIRINOX in patients with BRPC and LAPC. Methods: This single-center retrospective analysis included a total of 199 consecutive patients with BRPC or LAPC who received conventional or modified FOLFIRINOX between February 2013 and January 2017. An independent radiologist reviewed all baseline computed tomography or magnetic resonance imaging scans were reviewed for vascular invasion status. Results: With median follow-up duration of 40.3 months [95% confidence interval (CI), 36.7–43.8] in surviving patients, median progression-free survival (PFS) and overall survival (OS) were 10.6 (95% CI, 9.5–11.7) and 18.1 (95% CI, 16.0–20.3) months, respectively. The 1-year PFS rate was 66.0% (95% CI, 65.3–66.7%), and the 2-year OS rate was 37.2% (95% CI, 36.5–37.9%). PFS and OS did not differ between BRPC and LAPC groups [median PFS, 11.1 months (95% CI, 8.8–13.5) versus 10.1 months (95% CI, 8.4–11.8), p = 0.47; median OS, 18.4 months (95% CI, 16.1–20.8) versus 17.1 months (95% CI, 13.2–20.9), p = 0.50]. Curative-intent conversion surgery (R0/R1) was performed in 63 patients (31.7%). C•A 19-9 response, objective tumor response to FOLFIRINOX, and conversion surgery were independent prognostic factors for OS. Conclusion: FOLFIRINOX was effective for management of BRPC and LAPC. Given the potential for cure, a significant proportion of patients can undergo conversion curative-intent surgery following FOLFIRINOX.

Background Although endoscopic ultrasound (EUS) features and criteria have been described in chronic pancreatitis, challenges remain with interoperator variability and ease of adoption. The aim of this study was to define and validate the EUS features of chronic pancreatitis in a multicenter prospective study in Asia. Method The study was divided into two parts: the first part was conducted to derive the EUS features of chronic pancreatitis with adequate interoperator agreement; the second was to prospectively evaluate these features in a multicenter cross-sectional study and determine the optimal combination of features for the diagnosis of chronic pancreatitis. Prospectively enrolled cases had standard internationally validated radiologic or histologic features of chronic pancreatitis, and controls were patients without chronic pancreatitis who underwent EUS examination. Results The top six EUS features that had good interobserver agreement (mean kappa 0.73, range 0.60 – 0.90) were selected to be further evaluated in part II of the study. These included: hyperechoic foci with shadowing, lobularity with honeycombing, cysts, dilated main pancreatic duct, dilated side branches, and calculi in the main pancreatic duct. A total of 284 subjects (132 cases, 152 controls) were enrolled from 12 centers in Asia. All six features had high accuracy ranging from 63.3 % to 89.1 %. Two or more of these six EUS features accurately defined chronic pancreatitis (sensitivity 94.7 %, specificity 98.0 %), with an area under the receiver operating curve of 0.986. Conclusion This multicenter Asian study characterized and defined the EUS features of chronic pancreatitis. This provides a useful tool in clinical practice and further research in pancreatic cancer surveillance.

7 páginas Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is the etiologic agent causing the disease Corona Virus Disease 19 (COVID-19), resulting in a worldwide pandemic. Non-emergent endoscopy services have been disrupted as incidence and hospitalizations were rising. It is anticipated that the peak incidence may be leveling off in many parts of the world, but there is a concern for resurgence of the virus activity. Thus, it is important for endoscopy units to have plans in place during peak times of the epidemic and when resuming endoscopic services as the pandemic wanes. The global endoscopy community is faced with the challenge of providing care during this time. The WEO-COVID guidance task force has provided this resource document based on the current evidence and consensus opinion. These World Endoscopy Organization (WEO) recommendations are meant to guide endoscopists worldwide, should be interpreted in light of specific clinical conditions and resource availability and may not apply in all situations. This guidance document does not supersede the need to check for all local regulations and legislations.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Background Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. Methods This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. Results 289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. Conclusion In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.

Background and Objectives: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and fine needle biopsy (FNB) are effective techniques that are widely used for tissue acquisition. However, it remains unclear how to obtain high-quality specimens. Therefore, we conducted a survey of EUS-FNA and FNB techniques to determine practice patterns worldwide and to develop strong recommendations based on the experience of experts in the field. Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS Task Force (ISEUS-TF). The survey was administered by E-mail through the SurveyMonkey website. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Another questionnaire about the level of recommendation was designed to assess the respondents' answers. Results: ISEUS-TF members developed a questionnaire containing 17 questions that was sent to 53 experts. Thirty-five experts completed the survey within the specified period. Among them, 40% and 54.3% performed 50–200 and more than 200 EUS sampling procedures annually, respectively. Some practice patterns regarding FNA/FNB were recommended. Conclusion: This is the first worldwide survey of EUS-FNA and FNB practice patterns. The results showed wide variations in practice patterns. Randomized studies are urgently needed to establish the best approach for optimizing the FNA/FNB procedures.

BACKGROUND AND AIM Few studies compared endoscopic ultrasound (EUS)-guided fine needle aspiration (EUS-FNA) with endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling in terms of diagnostic accuracy in suspected malignant biliary obstruction. We evaluated and compared the diagnostic performance of EUS-FNA and ERCP-based tissue sampling. METHODS This multicenter study included 263 patients with suspected malignant biliary obstruction who underwent same-session EUS and ERCP between 2012 and 2016. RESULTS Malignancies were confirmed in 239 patients (90.9%) and benign in 24 patients (9.1%). Overall diagnostic sensitivity and accuracy were 73.6% and 76.1% for EUS-FNA, 56.5% and 60.5% for ERCP, and 85.8% and 87.1% for EUS/ERCP combination. EUS-FNA showed higher overall performances compared with ERCP (P

OBJECTIVES There is an increasing need for grading with small endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) specimens for the proper diagnosis and therapy selection of patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, our understanding of EUS-FNAB specimen grading is limited compared with surgically resected specimens. METHODS We retrospectively determined Ki-67 labeling index (LI) of 33 matched EUS-FNAB and surgically resected PanNETs with digital image analyzer. Pairwise grades between the matched biopsy and surgically resected PanNET specimens were compared. RESULTS The mean Ki-67 LI was higher in surgically resected PanNET specimens (5.5%) than in biopsy specimens (3.2%; P = 0.022). There was moderate agreement between the Ki-67 LI grades when individually evaluated matched biopsy and resected specimen pairs were compared (κ value = 0.62; P < 0.0001). However, discordance was noted in 6 cases (18%), and all of them were either grade 2 or 3 in resected PanNETs. CONCLUSIONS Although Ki-67 LI grading of EUS-FNAB specimens may be concordant with that of matched surgically resected specimens in a large proportion of the PanNET cases, Ki-67 LI grading of EUS-FNAB specimens should be carefully applied in clinical practice because of the possibility of grading underestimation with grade 2 to 3 PanNET cases.

Purpose Pancreatic cancer associated double primary tumors are rare and their clinicopathologic characteristics are not well elucidated. Materials and methods Clinicopathologic factors of 1,352 primary pancreatic cancers with or without associated double primary tumors were evaluated. Results Of resected primary pancreatic cancers, 113 (8.4%) had associated double primary tumors, including 26 stomach, 25 colorectal, 18 lung, and 13 thyroid cancers. The median interval between the diagnoses of pancreatic cancer and associated double primary tumors was 0.5 months. Overall survival (OS) of pancreatic cancer patients with associated double primary tumors was longer than those with pancreatic cancer only (median, 23.1 months vs. 17.0 months, p=0.002). Patients whose pancreatic cancers were resected before the diagnosis of metachronous tumors had a better OS than patients whose pancreatic cancer resected after the diagnosis of metachronous tumors (48.9 months and 13.5 months, p=0.001) or those whose pancreatic cancers were resected synchronously with non-pancreas tumors (19.1 months, p=0.043). The OS of pancreatic cancer patients with stomach (33.9 months, p=0.032) and thyroid (117.8 months, p=0.049) cancers was significantly better than those with pancreas cancer only (17.0 months). Conclusion About 8% of resected pancreatic cancers had associated double primary tumors, and those from the colorectum, stomach, lung, and thyroid were common. Patients whose pancreatic cancer was resected before the diagnosis of metachronous tumors had better OS than those resected after the diagnosis of metachronous tumors or those resected synchronously.

Endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) may facilitate tissue acquisition for a definitive diagnosis of gastrointestinal subepithelial tumors (SETs). This study aimed to determine the diagnostic yield of EUS-FNB using a novel 20-gauge ProCore needle with a coiled sheath in tissue sampling of gastrointestinal SETs. Between July 2016 and February 2017, 39 patients with gastrointestinal SETs were prospectively recruited from six university hospitals in Korea. Hypoechoic SETs ≥2 cm in size and originating from the submucosal and/or muscularis propria layer under EUS were eligible. This study was registered on ClinicalTrials.gov (NCT02884154). A total of 36 patients were included in the final analyses. EUS-FNB was diagnostic in 88.9% of SETs. Tissue adequacy was judged as optimal in 97.2% of FNB specimens according to on-site visual evaluation by endosonographers, and in 88.9% of specimens according to pathologists. A macroscopically optimal core sample was obtained with two needle passes in 94.4% of cases. Technical failure rate was encountered in two cases (5.6%) after two needle passes. There were two cases (5.6%) of bleeding, which was managed endoscopically. EUS-FNB using a 20-gauge ProCore needle is a technically feasible and effective modality for histopathologic diagnosis of gastrointestinal SETs, providing adequate core samples with fewer needle passes; ClinicalTrials.gov number, NCT02884154.

OBJECTIVES:The goal of the study was to determine whether endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is comparable to conventional transpapillary stenting with endoscopic retrograde cholangiopancreatography (ERCP) in palliation of malignant distal biliary obstruction. Although ERCP

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 impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC. A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included. All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44–0.67; p

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.

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.

Real-time guidance of needle advancement has transformed endoscopic ultrasound (EUS) from a diagnostic to an interventional procedure. EUS-guided fine-needle puncture has application in various interventional procedures (drainage of pseudocyst, biliary intervention, and injection of drugs). Celiac plexus or ganglion neurolysis for pain control is the major current EUS-guided fine-needle injection procedure. Feasibility and safety to accurately position needle devices and/or inject under real-time EUS imaging with precise delivery of interventional agent have expanded the use of EUS to ablate tumors. These include radiofrequency ablation, or delivery of fiducial markers, potential antitumor agents, or radioactive seeds, in the cancer mass. Minimally invasive EUS-guided antitumor therapy is primarily used for pancreatic cancer because of better anatomic access (vs other imaging modality) and the dismal prognosis (despite improvements in surgery and chemoradiation). Also, the response to parenteral chemotherapy in pancreatic cancer is poor because of suboptimal drug delivery resulting from hypovascularity and abundant desmoplasia. Other targets for EUS-guided tumor ablation are pancreatic neuroendocrine tumor and pancreatic cyst lesion, which are less aggressive and curable by resection. However, patients non-eligible for surgery may benefit from local EUS-guided ablation.