Anti-fibrotic and anti-stricture effects of biodegradable biliary stents braided with dexamethasone-impregnated sheath/core structured monofilaments.

Endoscopic biliary stent insertion has been widely used for the treatment of benign biliary stricture (BBS). Thus, the development of stent materials in the perspectives of structure, mechanical properties, and biocompatibility has been also studied. However, conventional metal and plastic stents have several disadvantages, such as repeated procedures to remove or exchange them, dislodgment, restenosis, biocompatibility, and poor mechanical properties. Sustainable effectiveness, attenuation and prevention of fibrosis, and biocompatibility are key factors for the clinical application of stents to BBS treatment. In addition, loading drugs could show synergistic effects with stents' own performance. We developed a dexamethasone-eluting biodegradable stent (DBS) consisting of a sheath/core structure with outstanding mechanical properties and sustained release of dexamethasone, which maintained its functions in a BBS duct over 12 weeks in a swine model. The insertion of our DBS not only expanded BBS areas but also healed secondary ulcers as a result of the attenuation of fibrosis. After 16 weeks from the insertion, BBS areas were totally improved, and the DBS was degraded and thoroughly disappeared without re-intervention for stent removal. Our DBS would be an effective clinical tool for non-vascular diseases. STATEMENT OF SIGNIFICANCE: This study describes the insertion of a drug-eluting biodegradable stent (DBS) into the bile duct. The sheath/core structure of DBS confers substantial durability and a sustained drug release profile. Drug released from the DBS exhibited anti-fibrotic effects without inflammatory responses in both in vitro and in vivo experiments. The DBS maintained its function over 12 weeks after insertion into the common bile duct, expanding benign biliary stricture (BBS) and reducing inflammation to heal secondary ulcers in a swine BBS model. After 16 weeks from the DBS insertion, the DBS thoroughly disappeared without re-intervention for stent removal, resulting in totally improved BBS areas. Our findings not only spotlight the understanding of the sheath/core structure of the biodegradable stent, but also pave the way for the further application for non-vascular diseases.

Randomized Trial of Prophylactic Antibiotics for Endoscopic Retrograde Cholangiopancreatography in Patients With Biliary Obstruction.

INTRODUCTION: The incidence of postendoscopic retrograde cholangiopancreatography (ERCP) infections is reported to be up to 18% in patients with biliary obstruction. Antibiotic prophylaxis may reduce the risk of infectious complications after ERCP; however, the clinical value of prophylactic antibiotics in ERCP remains controversial. METHODS: We conducted a double-blind, placebo-controlled, randomized trial to investigate whether the use of prophylactic antibiotics would reduce infectious complications after ERCP in patients with biliary obstruction. We randomly assigned patients in a 1:1 ratio to receive either a single dose of 1 g intravenous cefoxitin or normal saline as a placebo 30 minutes before undergoing ERCP. The primary outcome was the incidence of infectious complications after ERCP. RESULTS: We enrolled 378 patients, and 189 patients were assigned to each group. The risk of infectious complications after ERCP was 2.8% (5 of 176 patients) in the antibiotic prophylaxis group and 9.8% (17 of 173 patients) in the placebo group (risk ratio, 0.29; 95% confidence interval [CI], 0.11-0.74, P = 0.0073). The incidence rates of bacteremia were 2.3% (4 of 176 patients) and 6.4% (11 of 173 patients), respectively (risk ratio, 0.36; 95% CI, 0.12-1.04; P = 0.0599). The incidence rate of cholangitis was 1.7% (3 of 176 patients) in the antibiotic prophylaxis group and 6.4% (11 of 173 patients) in the placebo group (risk ratio, 0.27; 95% CI, 0.08-0.87; P = 0.0267). DISCUSSION: Antibiotic prophylaxis before ERCP in patients with biliary obstruction resulted in a significantly lower risk of infectious complications, especially cholangitis, than placebo ( ClinicalTrials.gov trial number NCT02958059).

Comparison of Physician-Controlled Maneuver and Assistant-Controlled Maneuver during Endoscopic Retrograde Cholangiopancreatography.

PURPOSE: Cannulation of the major papilla is the most challenging part of endoscopic retrograde cholangiopancreatography (ERCP) for which physician-controlled wire-guided cannulation (PCWGC) and assistant-controlled wire-guided cannulation (ACWGC) are used as the cannulation techniques. PCWGC can reportedly save up to about 30% of the labor cost by reducing the number of assistants. This study aims to compare the safety and efficacy of PCWGC and ACWGC. MATERIALS AND METHODS: Of the 2151 patients aged >20 years (4193 cases) who underwent ERCP at Yonsei University Medical Center between January 2015 and December 2016, 989 were included in this study. RESULTS: Among efficacy outcomes, cannulation success rate, rate of precut sphincterotomy (PCWGC vs. ACWGC: 21.3% vs. 25.9%), bile duct cannulation time (PCWGC vs. ACWGC: median 3.0 minutes vs. 3.6 minutes), and total procedure time (PCWGC vs. ACWGC: median 13.6 minutes vs. 13.1 minutes) were not significantly different. Among safety outcomes, lower rates of post-ERCP pancreatitis were observed with PCWGC than with ACWGC (PCWGC vs. ACWGC: 5.8% vs. 8.8%, p=0.128). Among other post-ERCP adverse events (bleeding, perforation, and cholangitis), the difference was not significant between the groups. Radiation exposure (total dose area product, PCWGC vs. ACWGC: median 1979.9 µGym² vs. 2062.0 µGym², p=0.194) and ERCP cost excluding labor cost (PCWGC vs. ACWGC: $1576 vs. $1547, p=0.606) were not significantly different. CONCLUSION: Requiring less assistants, PCWGC showed comparable efficacy and safety to ACWGC. PCWGC can be considered as an alternative option, especially in facilities lacking manpower and resources.

Efficacy of a Newly Developed Guidewire for Selective Biliary Cannulation: A Multicenter Randomized Controlled Trial.

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

Efficacy Analysis of Suprapapillary versus Transpapillary Self-Expandable Metal Stents According to the Level of Obstruction in Malignant Extrahepatic Biliary Obstruction.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS. Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively. Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV. Conclusions: The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

Difference of Risk of Pancreatic Cancer in New-Onset Diabetes and Long-standing Diabetes: A Population-based Cohort Study.

CONTEXT: Considering the absence of methods to find pancreatic cancer early, surveillance of high-risk groups is needed for early diagnosis. OBJECTIVE: The study aimed to investigate the effect in the incidence of pancreatic cancer and the differences between new-onset diabetes mellitus (NODM) and long-standing DM (LSDM) since NODM group is a representative high-risk group. METHODS: The Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013 data were used. Regarding 88 396 people with DM (case group), we conducted a 1:1 propensity score matching to select a matched non-DM population (control group). To investigate the interaction between DM and the time variable distinguishing NODM and LSDM, we performed a multivariate time-dependent Cox regression analysis. RESULTS: The incidence of pancreatic cancer was higher in the DM group compared to the non-DM group (0.52% vs 0.16%; P < .001). The DM group had shown different risk of pancreatic cancer development according to the duration since the DM diagnosis (NODM hazard ratio (HR): 3.81; 95% CI, 2.97-4.88; P < .001; LSDM HR: 1.53; 95% CI, 1.11-2.11; P < .001). When the NODM and the LSDM groups were compared, the risk of pancreatic cancer was higher in the NODM group than in the LSDM group (HR: 1.55; P = .020). In subgroup analysis, NODM group showed that men (HR = 4.42; 95% CI, 3.15-6.19; P < .001) and patients who were in their 50 seconds (HR = 7.54; 95% CI, 3.24-17.56; P < .001) were at a higher risk of developing pancreatic cancer than matched same sex or age control group (non-DM population), respectively. CONCLUSION: The risk of pancreatic cancer was greater in people with DM than in a non-DM population. Among people with DM, NODM showed a higher risk of pancreatic cancer than LSDM.

Evaluation of the 8th Edition AJCC Staging System for the Clinical Staging of Pancreatic Cancer.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.

Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer.

Some BTC types respond to pembrolizumab, but there are no known prognostic factors to predict its treatment benefits. In this study, we attempted to identify the prognostic factors associated with pembrolizumab as a second-line treatment for gemcitabine-refractory BTC. This retrospective and single tertiary-center study involved all the consecutive patients (n = 80) with refractory advanced BTC, who were diagnosed as programmed cell death ligand 1-positive and treated with pembrolizumab between August 2017 and February 2021. The overall survival (OS) was analyzed using Cox regression analysis. The median OS was 6.0 months [95% confidence interval (CI): 3.87−8.20]; median progression-free survival was 1.9 months (95% CI: 1.82−1.98); and the response rate was 15.9%. In the multivariate Cox regression analysis, the TB [adjusted hazard ratio (HR) = 2.286; 95% CI: 1.177−4.440; p = 0.015), albumin levels (adjusted HR = 0.392; 95% CI: 0.211−0.725; p = 0.003), ALP levels (adjusted HR = 1.938; 95% CI: 1.105−3.400; p = 0.021), and LMR (adjusted HR = 0.325; 95% CI: 0.173−0.609; p < 0.001) were identified as significant variables associated with the OS. High albumin levels and LMR and low ALP levels and TB were significantly associated with better OS in patients treated with pembrolizumab.

Optimal reproduction of a porcine benign biliary stricture model using endobiliary radiofrequency ablation.

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

Comparison of the Malignant Predictors in Intrahepatic and Extrahepatic Intraductal Papillary Neoplasm of the Bile Duct.

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

Preventive effect of biodegradable stents on biliary stricture and fibrosis after biliary anastomosis in a porcine model.

PURPOSE: The current drain tubes for preventing surgically biliary anastomotic stricture are not naturally and easily removed. If a drain tube using biodegradable material is easily available and the degradation time of the tube is well controlled, surgical anastomotic stricture and fibrosis could be prevented. The aim of this animal study was to evaluate the preventive effect of novel biodegradable stents (BS) on biliary stricture and fibrosis after duct-to-duct (DD) biliary anastomosis. METHODS: Ten mini-pigs were allocated to the control group (n = 5) and or the stent group (n = 5). The common bile duct was exposed through surgical laparotomy and then resected transversely. In the stent group, a 4-mm or 6-mm polydioxanone/magnesium sheath-core BS was inserted according to the width of the bile duct, followed by DD biliary anastomosis. In the control group, DD biliary anastomosis was performed without BS insertion. RESULTS: In the stent group, stents were observed without deformity for up to 4 weeks in all animals. Eight weeks later, histopathologic examination revealed that the common bile duct of the anastomosis site was relatively narrower in circumference in the control group compared to the stent group. The degree of fibrosis in the control group was more marked than in the stent group (3.84 mm vs. 0.68 mm, respectively; P < 0.05). CONCLUSION: Our study showed that novel BS maintained their original shape and radial force for an adequate time and then disappeared without adverse events. The BS could prevent postoperative complications and strictures after DD biliary anastomosis.

Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis.

BACKGROUND/AIMS: : Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. METHODS: We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. RESULTS: Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. CONCLUSIONS: We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

Predictors of Sarcopenia in an Obese Asian Population.

Sarcopenia is associated with obesity and might also be responsible for other disorders. Here, we investigated the prevalence of sarcopenia and its predictors in obese subjects. Subjects who underwent a medical health checkup and living-related liver donors were recruited. Obesity was defined as body mass index (BMI) ≥25 kg/m2. Muscle mass was assessed using computed tomography at the 3rd lumbar vertebra. The lowest quartile of the lumbar skeletal muscle index (LSMI) was considered sarcopenia. Among 466 obese subjects, 53 (11.4%) had sarcopenia. Subjects with sarcopenia were significantly older (mean 66.6 vs. 53.3 years) and had a significantly higher prevalence of hypertension (62.3 vs. 46.0%) and diabetes (45.3 vs. 31.0%), higher fibrosis-4 (FIB-4) index (mean 1.57 vs. 1.16), and higher atherosclerotic cardiovascular disease (ASCVD) risk score (mean 22.86% vs. 11.15%), whereas they had a significantly lower prevalence of female gender (13.2% vs. 27.8%), lower BMI (mean 26.4 vs. 27.4 kg/m2), and lower LSMI (mean 43 vs. 56 cm2/m2) than subjects without sarcopenia (all P < 0.05). On multivariate analysis, higher BMI (odd ratio [OR] = 0.599, P = 0.001) was independently associated with a reduced risk of sarcopenia, whereas higher ASCVD risk scores (OR = 1.045, P < 0.001) were independently associated with an increased risk of sarcopenia. Sarcopenia is significantly associated with lower BMI and higher cardiovascular risk in an obese Asian population.

Usefulness of Smartphone Apps for Improving Nutritional Status of Pancreatic Cancer Patients: Randomized Controlled Trial.

BACKGROUND: Approximately 80% of pancreatic ductal adenocarcinoma (PDAC) patients suffer from anorexia, weight loss, and asthenia. Most PDAC patients receive chemotherapy, which often worsens their nutritional status owing to the adverse effects of chemotherapy. Malnutrition of PDAC patients is known to be associated with poor prognosis; therefore, nutritional management during chemotherapy is a key factor influencing the outcome of the treatment. Mobile apps have the potential to provide readily accessible nutritional support for patients with PDAC. OBJECTIVE: We aimed to evaluate the efficacy of a mobile app-based program, Noom, in patients receiving chemotherapy for PDAC. METHODS: We prospectively enrolled 40 patients who were newly diagnosed with unresectable PDAC from a single university-affiliated hospital in South Korea, and randomly assigned them into a Noom user group (n=20) and a non-Noom user group (n=20). The 12-week in-app interventions included meal and physical activity logging as well as nutritional education feedback from dietitians. The non-Noom user group did not receive any nutrition intervention. The primary outcomes were the changes in the nutritional status and quality of life (QoL) from the baseline to 12 weeks. The secondary outcomes included the changes in the skeletal muscle index (SMI) from the baseline to 12 weeks. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Patient-Generated Subjective Global Assessment (PG-SGA) were used as paper questionnaires to assess the QoL and nutritional status of the patients. Intention-to-treat and per-protocol analyses were conducted. Regarding the study data collection time points, we assessed the nutritional status and QoL at the baseline (T0), and at 4 (T1), 8 (T2), and 12 (T3) weeks. Abdominal computed tomography (CT) imaging was conducted at the baseline and after 8 weeks for tumor response and SMI evaluation. The skeletal muscle area (cm2) was calculated using routine CT images. The cross-sectional areas (cm2) of the L3 skeletal muscles were analyzed. RESULTS: Between February 2017 and January 2018, 48 patients were assessed for eligibility. Totally 40 patients with pancreatic cancer were included by random allocation. Only 17 participants in the Noom user group and 16 in the non-Noom user group completed all follow-ups. All the study participants showed a significant improvement in the nutritional status according to the PG-SGA score regardless of Noom app usage. Noom users showed statistically significant improvements on the global health status (GHS) and QoL scales compared to non-Noom users, based on the EORTC QLQ (P=.004). The SMI decreased in both groups during chemotherapy (Noom users, 49.08±12.27 cm2/m2 to 46.08±10.55 cm2/m2; non-Noom users, 50.60±9.05 cm2/m2 to 42.97±8.12 cm2/m2). The decrement was higher in the non-Noom user group than in the Noom user group, but it was not statistically significant (-13.96% vs. -3.27%; P=.11). CONCLUSIONS: This pilot study demonstrates that a mobile app-based approach is beneficial for nutritional and psychological support for PDAC patients receiving chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04109495; https://clinicaltrials.gov/ct2/show/NCT04109495.

Optimal drainage of anastomosis stricture after living donor liver transplantation.

BACKGROUND: Endoscopic biliary stenting (EBS) with a fully covered, self-expandable metallic stent (FC-SEMS) and plastic stent (PS) is safe and efficient for biliary anastomotic strictures (ASs) after a deceased donor liver transplantation. Limited studies have investigated the use of FC-SEMSs for biliary strictures post-living donor liver transplantation (LDLT). We compared the resolution rate of biliary ASs post-LDLT and the 12-month recurrence rates post-stent removal between EBS with an FC-SEMS, PS, and percutaneous transhepatic biliary drainage (PTBD). METHODS: Patients with biliary ASs after an LDLT (mean age: 57.3 years, 76.1% men) hospitalized between 2014 and 2017 were enrolled. Endoscopic retrograde cholangiopancreatography (ERCP) was repeated every 3-4 months. Patients were followed-up for at least 1-year post-stent removal. RESULTS: Of the 75 patients enrolled, 16, 20, and 39 underwent EBS with an FC-SEMS, PS, and PTBD, respectively. Median follow-up period was 39.2 months. Fewer ERCP procedures were needed in the FC-SEMS group than in the PS group (median, 2 vs. 3; P = 0.20). Median stent indwelling periods were 4.7, 9.3, and 5.4 months in the FC-SEMS, PS, and PTBD groups, respectively (P = 0.006). The functional resolution rate was lower in the PS group (16/20) than in the FC-SEMS (16/16) or PTBD (39/39) group (P = 0.005). The radiologic resolution rate was higher in the FC-SEMS group (16/16) than in the PS group (14/20) (P = 0.07). The 12-month recurrence rates showed no significant differences (FC-SEMS, 4/16; PS, 3/16; PTBD, 6/39; P = 0.66). The rates of complications during treatment differed significantly between the groups (P = 0.04). Stent migration occurred in 1 (6.3%) and 5 (25.0%) patients in the FC-SEMS and PS groups, respectively (P = 0.59). CONCLUSIONS: EBS with an FC-SEMS is comparable with EBS with a PS or PTBD in terms of biliary stricture resolution and 12-month recurrence rates. The use of FC-SEMSs is potentially effective and safe for biliary AS resolution after LDLT.

Radiographic portal or superior mesenteric vein invasion is an independent prognostic factor in non-metastatic pancreatic ductal adenocarcinoma: A missing block of clinical T staging?

BACKGROUND: Venous invasion is not included in the pancreatic ductal adenocarcinoma (PDAC) staging, and its correlation with prognosis remains unclear. We evaluated the prognostic impact of radiographic portal/superior mesenteric vein (PV/SMV) invasion, and its possibility of complementing T staging. METHODS: We identified patients with non-metastatic PDAC using our institutional cohort, and divided them according to PV/SMV invasion at imaging, defined as >180-degree tumor-vessel interface or contour deformity. We conducted Cox proportional hazard regression, and compared survival in the original and 1:1 propensity score matched datasets. RESULTS: We identified 454 patients [PV/SMV(+): 172; PV/SMV(-): 282]. In the multivariate analysis, PV/SMV invasion, age (≥70 years), performance status, tumor size (2-4, >4 cm), lymph nodes >4, and arterial invasion was correlated with prognosis. The PV/SMV(+) group had a shorter overall survival (OS) than the PV/SMV(-) group in the original (14.4 vs. 20.9 months; P < 0.001) and matched datasets (14.3 vs. 17.2 months; P = 0.009). Among patients without arterial invasion (cT1-cT3), the PV/SMV(+) group had a shorter OS (15.9 vs. 21.2 months; P = 0.002). Moreover, their OS did not differ from that of patients with arterial invasion (cT4) (15.9 vs. 14.4 months; P = 0.907). Patients with vessel (artery/vein) invasion had a shorter OS than those without vessel invasion (14.5 vs. 21.2 months; P < 0.001). CONCLUSIONS: Radiographic PV/SMV invasion in non-metastatic PDAC was correlated with a poor prognosis. It could identify a group with shorter OS among patients without arterial invasion (cT1-cT3). It is suggested that inclusion of PV/SMV invasion in clinical T4 criteria should be considered.

Sarcopenia Is Independently Associated with the Degree of Liver Fibrosis in Patients with Type 2 Diabetes Mellitus.

Background/Aims: Sarcopenia is associated with liver fibrosis in patients with nonalcoholic fatty liver disease and chronic hepatitis B. We investigated the association between sarcopenia and hepatic fibrotic burden in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM who had received a comprehensive medical health checkup were recruited. Muscle mass was assessed using computed tomography. Fibrotic burden was assessed using the fibrosis-4 index (FIB-4). The study population was divided by quartile stratification of the lumbar skeletal muscle index (LSMI). Results: Among 309 patients with T2DM, 75 (24.3%) had sarcopenia. These patients were significantly older and had higher FIB-4, whereas they had significantly lower body mass index (BMI) and LSMI than patients without sarcopenia (all p<0.05). The LSMI showed a significant negative correlation with the FIB-4 when analyzed in terms of quartile stratification (p=0.003). Multivariate analysis showed that female sex and higher BMI were independently associated with a reduced risk of sarcopenia (odds ratio [OR], 0.388; 95% confidence interval [CI], 0.199 to 0.755 and OR, 0.704; 95% CI, 0.618 to 0.801; all p<0.05), whereas a higher FIB- 4 was independently associated with an increased risk of sarcopenia (OR, 1.817; 95% CI, 1.180 to 2.797; p=0.007). Among patients with a BMI <25 kg/m2 (n=165), those with sarcopenia (n=54, 32.7%) had a significantly higher FIB-4 than those without (n=111, 67.3%; 1.66 vs 1.38, p=0.004). Conclusions: Sarcopenia is independently associated with fibrotic burden in patients with T2DM. Further studies should investigate whether the improvement of sarcopenia can ameliorate liver fibrosis in patients with T2DM.

Discordant sleep parameters among actigraphy, polysomnography, and perceived sleep in patients with sleep-disordered breathing in comparison with patients with chronic insomnia disorder.

PURPOSE: Although the clinical usefulness of actigraphy (ACT) in chronic insomnia disorder (CID) is extensively investigated, the evaluation on the utility of ACT in sleep-disordered breathing (SDB) is limited and the report of comparison with perceived sleep by patients and polysomnography (PSG) is scarce. METHODS: Thirty-six patients with SDB and 30 with CID underwent PSG and ACT, and they reported perceived sleep time and latency simultaneously. Sleep parameters (total sleep time [TST], sleep onset latency [SOL], sleep efficiency, and wakefulness after sleep onset [WASO]) were compared. Agreement among parameters was assessed with intraclass correlation coefficient (ICC) and 95% confidence interval. RESULTS: ACT overestimated TST and underestimated SOL and WASO relative to PSG in both groups. Perceived sleep was commonly undervalued relative to PSG or ACT. In post hoc analyses, perceived sleep was significantly shorter and SOL significantly longer compared to PSG and ACT in both groups. Perception of sleep time by PSG was significantly higher than perception by ACT. In the CID group, all sleep parameters were significantly correlated between ACT and PSG (ICC = 0.627-0.813). In the SDB group, only TST was significantly correlated (ICC = 0.804). CONCLUSION: ACT is useful to monitor sleep and sleep quality in patients with CID. In patients with SDB, TST by ACT is reliable. However, ACT is insufficient to assess sleep quality due to its low agreement with PSG. Significantly lower sleep perception relative to PSG and ACT should be considered in the treatment of sleep disorders.

Does psychopathology in childhood predict internet addiction in male adolescents?

This study investigated childhood psychopathology and Internet addiction in adolescents. Initial assessment data were obtained from 1998 to 1999, and a follow-up assessment was performed in 2006, when the original subjects entered middle school. Personal information for the 524 male subjects was obtained from the original data. The subjects were evaluated with the Korean version of the child behavior checklist, which was administered to the children's parents. Demographic and psychosocial factors were also evaluated. Children were reassessed with the self-reported Korea Internet Addiction Scale. Our results indicated that 3.6 % of the subjects had Internet addiction, and revealed a significant relationship between withdrawal and anxiety/depression and future Internet addiction. The results suggest that withdrawal and anxiety/depression during childhood should be considered in the etiology of problematic Internet use in boys. Accordingly, clinicians should consider anxiety/depression and withdrawal during childhood to prevent Internet addiction.