Feasibility of in vivo swine models using guide wire-assisted intraductal radiofrequency ablation for benign biliary stricture.

Several in vivo swine models of benign biliary stenosis (BBS) have been recently reported for preclinical studies of novel endoscopic techniques and devices. The aim of this study was to evaluate the efficacy and feasibility of large animal models of BBS by using intraductal radiofrequency ablation (RFA) assisted by guide wire. Six in vivo swine models were made by using an intraductal RFA for cauterization at 10 W, 80 °C, 90 s in the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography (ERCP) was performed with cholangiography and histologic evaluation was done for the common bile duct. Blood tests were examined before, after, and at the final follow-up. Guide wire assisted RFA electrode produced BBS in all (6/6, 100%) animal models without severe complications. Fluoroscopy findings at 2 weeks after intraductal RFA in every model revealed BBS in the common bile duct. In histologic evaluations, fibrosis and chronic inflammatory changes were noted. After the procedure, ALP, GGT, and CRP were elevated and decreased after an appropriate drain. A swine model of BBS is developed by inducing intraductal thermal injury using intraductal RFA assisted by guide wire. This novel technique for inducing BBS in swine is effective and feasible.

pH and Redox-Dual Sensitive Chitosan Nanoparticles Having Methyl Ester and Disulfide Linkages for Drug Targeting against Cholangiocarcinoma Cells.

The aim of this study is to prepare pH- and redox-sensitive nanoparticles for doxorubicin (DOX) delivery against DOX-resistant HuCC-T1 human cholangiocarcinoma (CCA) cells. For this purpose, L-histidine methyl ester (HIS) was attached to chitosan oligosaccharide (COS) via dithiodipropionic acid (abbreviated as ChitoHISss). DOX-incorporated nanoparticles of ChitoHISss conjugates were fabricated by a dialysis procedure. DOX-resistant HuCC-T1 cells were prepared by repetitive exposure of HuCC-T1 cells to DOX. ChitoHISss nanoparticles showed spherical morphology with a small diameter of less than 200 nm. The acid pH and glutathione (GSH) addition induced changes in the size distribution pattern of ChitoHISss nanoparticles from a narrow/monomodal distribution pattern to a wide/multimodal pattern and increased the fluorescence intensity of the nanoparticle solution. These results indicate that a physicochemical transition of nanoparticles can occur in an acidic pH or redox state. The more acidic the pH or the higher the GSH concentration the higher the drug release rate was, indicating that an acidic environment or higher redox states accelerated drug release from ChitoHISss nanoparticles. Whereas free DOX showed decreased anticancer activity at DOX-resistant HuCC-T1 cells, DOX-incorporated ChitoHISss nanoparticles showed dose-dependent anticancer activity. Intracellular delivery of DOX-incorporated ChitoHISss nanoparticles was relatively increased at an acidic pH and in the presence of GSH, indicating that DOX-incorporated ChitoHISss nanoparticles have superior acidic pH- and redox-sensitive behavior. In an in vivo tumor xenograft model, DOX-incorporated ChitoHISss nanoparticles were specifically delivered to tumor tissues and then efficiently inhibited tumor growth. We suggest that ChitoHISss nanoparticles are a promising candidate for treatment of CCA.

Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells.

The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 was conjugated with mPEG via selenocystamine linkage and then remaining carboxylic acid groups of Ce6 was attached to PBAP (mPEGseseCe6PBAP conjugates). Nanophotosensitizers of mPEGseseCe6PBAP conjugates were prepared by dialysis method. In transmission electron microscope (TEM) observation, nanophotosensitizers of mPEGseseCe6PBAP conjugates have spherical shapes and their diameters were less than 150 nm. The average diameter of mPEGseseCe6PBAP nanophotosensitizers was 92.7 ± 9.6 nm in particle size analysis. When H2O2 was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H2O2 concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H2O2 concentration. When H2O2 was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H2O2 concentration, indicating that nanophotosensitizers showed ROS-sensitive delivery of Ce6 against cancer cells.As well as free Ce6, nanophotosensitizers in the absence of light irradiation have low intrinsic cytotoxicity against RAW264.7 cells and HeLa cells. However, nanophotosensitizers induced cell death dose-dependently under light irradiation. Especially, nanophotosensitizers showed significantly higher ROS generation and phototoxicity against HeLa cells in vitro. When nanophotosensitizers were intravenously administered to animal tumor xenograft model of HeLa cells, tumor tissues revealed stronger fluorescence intensity than other tissues by light irradiation while absence of light irradiation induced relatively lower fluorescence intensity in tumor tissues, indicating that nanophotosensitizers have sensitivity against oxidative stress in tumor tissues. We suggest that nanophotosensitizers of mPEGseseCe6PBAP conjugates are promising vehicle for PDT of cervical cancer cells.

Long-term Outcome of Endoscopic Retrograde Biliary Drainage of Biliary Stricture Following Living Donor Liver Transplantation.

Background/Aims: Biliary strictures remain one of the most challenging aspects after living donor liver transplantation (LDLT). The aim of this study was to assess long-term outcome of endoscopic treatment of biliary strictures occurring after LDLT and to identify risk factors of recurrent biliary strictures following endoscopic retrograde biliary drainage (ERBD) in LDLT. Methods: A total of 1,106 patients underwent LDLT from May 1995 to May 2014. We compared the risk factors between patients with and without recurrent biliary strictures. Results: Biliary strictures developed in 24.0% of patients. Technical success rate of ERBD for biliary stricture after LDLT was 66.2% (145/219). Among 145 patients managed by endoscopic drainage, stricture resolution occurred in 69 with median duration of stent indwelling of 13.6 months (range, 0.5 to 67.3 months), and stricture recurrence was seen in 20 (21.3%) out of 94. The median recurrence-free duration after final endoscopic success was 13.1 months (range, 0.5 to 67.3 months). Older donor age (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03 to 1.17; p=0.004) and non-B, non-C liver cirrhosis (HR, 5.10; 95% CI, 1.10 to 25.00; p=0.043) were associated with higher recurrence of biliary stricture. Conclusions: Long-term stricture resolution rate after ERBD insertion for biliary stricture occurring after LDLT was 73.4%. Clinicians should pay careful attention during following-up to decide when to remove ERBD in patients who have factors associated with recurrent biliary strictures.

Long-term outcome and recurrence factors after percutaneous cholecystostomy as a definitive treatment for acute cholecystitis.

BACKGROUND AND AIM: Percutaneous cholecystostomy (PC) has been frequently used as an alternative treatment for acute cholecystitis in seriously ill patients unfit for surgery. The aim of this study was to investigate the recurrence rate and risk factors of recurrence. METHODS: Medical records of 102 patients who were followed up for more than 1 year after PC tube removal among 716 patients who underwent PC for acute cholecystitis treatment were retrospectively analyzed. RESULTS: The recurrence rate of acute cholecystitis after PC tube removal was 20.6% (21/102), and the mean time to recur was 660 days. Underlying cancer (odds ratio [OR]: 3.369; 95% confidence interval [CI]: 1.006-11.282; P = 0.0489), PC duration shorter than 44 days (OR: 5.596; 95% CI: 1.35-23.201; P = 0.0176), and the presence of common bile duct stone in initial imaging studies (OR: 24.393; 95% CI: 2.696-220.746; P = 0.0045) were positively correlated with recurrence. Tubogram before PC tube removal did not significantly lower the recurrence. However, PC tube clamping for several days significantly lowered the recurrence (OR: 0.108; 95% CI: 0.015-0.794; P = 0.0288). Fifty-nine (57.8%) had acalculous cholecystitis. Calculous cholecystitis was negatively correlated with recurrence (OR: 0.267; 95% CI: 0.074-0.967; P = 0.0444). Receiver operating characteristic curve of the prediction model for recurrence verified its accuracy (area under the curve: 0.8475). CONCLUSION: We should try to keep PC more than 6 weeks and clamp for 1-2 weeks before removal. For those with the presence of common bile duct stones, calculous cholecystitis, and underlying malignancy, we should keep PC for longer duration and carefully observe symptoms and signs of recurrence.

Long term outcome of EUS-based strategy for suspected choledocholithiasis but negative CT finding.

OBJECTIVES: The American Society for Gastrointestinal Endoscopy (ASGE) guidelines offered the risk-stratified approach in suspected choledocholithiasis. Previous studies have raised concern about the insufficient accuracy of the guideline, especially in high probability group. The purposes of this study were to authenticate the stratification and clinical predictors of the guidelines for suspected choledocholithiasis with no visible choledocholithiasis on computed tomography (CT) and to make clear the clinical strategy of endoscopic ultrasonography (EUS). MATERIALS AND METHODS: We carried out the retrospective single-center study of 156 patients with suspected choledocholithiasis but negative findings on CT who underwent EUS for about 8 years at Samsung Medical Center. We assessed the clinical predictors of the ASGE guidelines in predicting the presence of choledocholithiasis and the outcome of the EUS. RESULTS: Fifty-three of the 156 patients had positive findings on EUS that included choledocholithiasis (n = 43, 27.6%) or obstructive papillitis (n = 10, 6.4%). Among the 53 patients, 51 (96.2%) had choledocholithiasis or obstructive papillitis on ERCP. The 101 patients of 103 patients with negative finding on EUS did not show biliary events during follow-up period. EUS accuracy was 98.7% (sensitivity 100%; specificity 98.1%). Among the 49 patients with high probability, 21 (42.9%) had choledocholithiasis on ERCP. In 107 patients who were classified as intermediate probability, 30 (27.3%) had choledocholithiasis. There were no complications related to EUS. CONCLUSIONS: Not only intermediate probability group but also high probability group without definite acute cholangitis may require EUS. Application of EUS for suspected choledocholithiasis is highly accurate, safe and reduces unnecessary invasive ERCP in 57.1% of patients with high probability group.

Efficacy of EUS-guided and ERCP-guided biliary drainage for malignant biliary obstruction: prospective randomized controlled study.

BACKGROUND AND AIMS: ERCP-guided biliary drainage (ERCP-BD) is a criterion standard treatment for malignant biliary obstruction when curative surgery is not an option. Alternative methods such as percutaneous transhepatic biliary drainage would significantly lower the quality of life. EUS-guided biliary drainage (EUS-BD) has been developed and performed by experienced endoscopists. Therefore, the aims of this study were to evaluate the efficacy and safety of EUS-BD compared with ERCP in malignant biliary obstruction. METHODS: The prospective randomized controlled study was conducted, and 30 patients were enrolled: 15 for each EUS-BD and ERCP-BD arms. The technical success, procedural time, clinical success, and adverse events were evaluated. RESULTS: Thirty patients had extrahepatic malignant biliary tract obstruction (19 men, 11 women). Twenty-seven patients had unresectable pancreatic ductal adenocarcinomas, 1 patient had distal common bile duct cancer, and 2 patients had metastatic malignant lymphadenopathy. There were no significant differences both in terms of technical success rate and clinical success rate (100% vs 93% and 93% vs 100% in ERCP-BD vs EUS-BD, respectively; P = 1.00, P = 1.00). Four patients (31%) had tumor ingrowth-caused stent dysfunction in the ERCP-BD group, whereas 2 patients had food impaction and 2 patients had stent migration in the EUS-BD group. No significant procedure-related adverse events occurred in either group. CONCLUSIONS: This prospective randomized controlled study suggests that EUS-BD has similar safety to ERCP-BD. EUS-BD was not superior to ERCP-BD in terms of relief of malignant biliary obstruction. EUS-BD may have fewer cases of tumor ingrowth but may also have more cases of food impaction or stent migration. (Clinical trial registration number: NCT01421836.).

Predictive Model for Neoplastic Potential of Gallbladder Polyp.

GOAL: To provide the statistical predictive model for neoplastic potential of gallbladder polyp (GBP). BACKGROUND: Many studies have attempted to define the risk factors for neoplastic potential of GBP. It remains difficult to precisely adapt the reported risk factors for the decision of surgery. Estimating the probability for neoplastic potential of GBP using a combination of several risk factors before surgical resection would be useful in patient consultation. STUDY: We collected data of patients confirmed as GBP through cholecystectomy at Samsung Medical Center between January 1997 and March 2015. Those with a definite evidence for malignancy, such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp >15 mm, and absence of proper preoperative ultrasonographic imaging were excluded. A total of 1976 patients were enrolled. To make and validate the predictive model, we divided the cohort into the modeling group (n=979) and validation group (n=997). Clinical information, ultrasonographic findings, and blood tests were retrospectively analyzed. RESULTS: Clinical factors of older age, single lesion, sessile shape, and polyp size showed statistical significance for neoplastic potential of GBP in the modeling group. A predictive model for neoplastic potential of GBP was constructed utilizing the statistical outcome of the modeling group. Statistical validation was performed with the validation group to determine the optimal clinical sensitivity and specificity of the predictive model. Optimal cut-off value for neoplastic probability was 7.4%. CONCLUSIONS: The predictive model for neoplastic potential of GBP may support clinical decisions before cholecystectomy.

[A Case of Biliary Obstruction Caused by Liver Cyst].

Most cystic lesions of the liver are found incidentally in imaging studies because they are not symptomatic, and generally do not require treatment. Rarely, however, symptomatic hepatic cysts may develop complications and require treatment. Here, we describe a case of a 77-year-old woman who developed biliary obstruction with abdominal pain due to compression of the bile duct by a simple hepatic cyst. We confirmed the diagnosis based on symptoms and imaging studies. The patient'ssymptoms improved after simple cyst ablation by sclerotherapy.

Stroke in a Young Individual with Left Ventricular Noncompaction and Left Atrium Standstill.

Isolated left ventricular noncompaction (LVNC) is a rare cardiomyopathy with morphologic characteristics of two distinct myocardial layers i.e., thin compacted epicardial and thick noncompacted endocardial layers. The noncompacted myocardium consists of prominent ventricular trabeculae and deep intertrabecular recesses. It can lead to arrhythmias, heart failure or systemic embolisms. Electrocardiographic patterns of patients with LVNC are various and non-specific; however, the most common findings are intraventricular conduction delay, left ventricular hypertrophy, and repolarization abnormalities. We reported the first case, to the best of our knowledge, of a 29-year-old man who had recent cerebral infarction and incidental LVNC with spontaneous left atrial standstill.

A case of ampullary gangliocytic paraganglioma.

Gangliocytic paragangliomas (GPs) are rare tumors of the duodenum, presenting as single sessile or pedunculated polypoid masses. Clinical manifestations of duodenal GPs can vary from an incidental finding at endoscopy to frequent upper gastrointestinal bleeding caused by mucosal ulceration and abdominal pain. GPs are considered benign, but the disease can recur and spread to regional lymph nodes. A 41-year-old female presented with abdominal pain. Upper gastrointestinal endoscopy revealed a subepithelial tumor of the ampulla of Vater in the second portion of the duodenum. The tumor was resected using the endoscopic mucosal resection technique. The tumor was diagnosed as benign GP of the duodenum using histological and immunohistochemical staining procedures.