Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis.

BACKGROUND/AIMS: The treatment of superficial esophageal neoplasms (SENs) in cirrhotic patients is challenging and rarely investigated. We evaluated the outcomes of endoscopic submucosal dissection (ESD) to determine the efficacy and safety of treating SENs in patients with liver cirrhosis. METHODS: The baseline characteristics and treatment outcomes of patients who underwent ESD for SENs between November 2005 and December 2017 were retrospectively reviewed. RESULTS: ESD was performed in 437 patients with 481 SENs, including 15 cirrhotic patients with 17 SENs. En bloc resection (88.2% vs. 97.0%) and curative resection (64.7% vs. 78.9%) rates were not different between the cirrhosis and non-cirrhosis groups (p=0.105 and p=0.224, respectively). Bleeding was more common in cirrhotic patients (p=0.054), and all cases were successfully controlled endoscopically. The median procedure and hospitalization duration did not differ between the groups. Overall survival was lower in cirrhotic patients (p=0.003), while disease-specific survival did not differ between the groups (p=0.85). CONCLUSION: ESD could be a safe and effective treatment option for SENs in patients with cirrhosis. Detailed preprocedural assessments are needed, including determination of liver function, esophageal varix status, and remaining life expectancy, to identify patients who will obtain the greatest benefit.

Comparison Between Redo Endoscopic Treatment and Surgery in Patients with Locally Recurrent Gastric Neoplasms.

BACKGROUND: Treatment of locally recurrent gastric neoplasms after endoscopic resection remains challenging. We investigated the efficacy and safety of treatment options for recurrent gastric neoplasms localized to the scar of previous endoscopic submucosal dissection (ESD). METHODS: The clinicopathological characteristics and treatment outcomes of patients who underwent endoscopic treatment or surgery for recurrent gastric neoplasms between June 2010 and May 2017 were retrospectively reviewed. RESULTS: Of the 92 patients included, 74 underwent endoscopic treatment (51 redo ESD, 23 argon plasma coagulation [APC] ablation) and 18 underwent surgery. The redo ESD procedure time was significantly longer than that of the primary ESD (31.0 versus 22.0 min, p = 0.018). Overall, adverse events occurred in 11 patients (12.0%), with the incidence being significantly higher in the surgery group (27.8% versus 8.1% in the endoscopic treatment group, p = 0.036). Local recurrence-free survival rates were 81.1% for the endoscopic treatment group (86.3% and 69.6% for redo ESD and APC groups, respectively) and 100% for the surgery group (log rank p = 0.033). Logistic regression analysis showed that tumor size > 12.5 mm (odds ratio [OR] 5.14, 95% confidence interval [CI] 1.25-26.9, p = 0.032) and tumors located in the upper two-thirds of the stomach (OR 4.43, 95% CI 1.27-16.8, p = 0.023) were associated with non-curative resection after redo ESD. CONCLUSIONS: Endoscopic treatment could be an effective and safe alternative to surgery for selected patients with gastric neoplasms recurring at the scar of previous ESD. Especially, patients having small lesions located in the distal part of the stomach could be a good candidate for redo ESD.

Eradication rate of Helicobacter pylori reinfection in Korea: A retrospective study.

BACKGROUND AND AIM: Guidelines for selecting the eradication regimen for Helicobacter pylori reinfection remain unclear. This study aimed to evaluate the eradication rate of H. pylori reinfection in patients with a previous infection successfully eradicated with index triple therapy. METHODS: This was a single-center, retrospective case-control study. A total of 10 468 H. pylori-infected patients treated with proton-pump inhibitor-based triple eradication therapy at a tertiary medical institution between 2005 and 2016 were enrolled. We reviewed the medical records of the enrolled patients and compared the treatment outcomes in those with H. pylori reinfection after a successful eradication. RESULTS: Helicobacter pylori infection was successfully eradicated with the index triple therapy in 7770 patients (74.2%). Among 3567 patients followed up for > 1 year, H. pylori reinfection occurred in 420 (11.8%; 3.06% per person-year) during a median follow-up of 39.1 months (interquartile range, 23.5-58.7 months). Of these patients, 164 received eradication therapy for reinfection (triple therapy in 102 and quadruple therapy in 62) and had follow-up data. Triple therapy showed an eradication rate of 78.4% for H. pylori reinfection, which was not significantly different from that of the index triple therapy (P = 0.394). Quadruple therapy for reinfection exhibited a better eradication rate (87.1%) than triple therapy but without statistical significance (P = 0.237). CONCLUSIONS: Retreatment with triple therapy for H. pylori reinfection after successful eradication of prior infection showed comparable outcomes to the index triple therapy. Bismuth-containing quadruple therapy for reinfection tended to have a better eradication rate than did triple therapy.

Outcomes of endoscopic submucosal dissection for gastric epithelial neoplasm in chronic kidney disease patients: propensity score-matched case-control analysis.

BACKGROUND: Little is known about the outcomes of gastric endoscopic submucosal dissection (ESD) in patients with chronic kidney disease (CKD). We compared the efficacy and safety of ESD between CKD and non-CKD patients. METHODS: From January 2005 to December 2014, 102 CKD patients underwent ESD for gastric neoplasms at a tertiary medical institution were reviewed retrospectively. A propensity score-matched control group (102 patients) was selected from non-CKD patients to compare clinical outcomes between CKD and non-CKD patients. RESULTS: En bloc resection (96.1%) and curative resection (88.2%) rates in the CKD group did not significantly differ from those in the non-CKD group. Median procedure times (25.0 vs. 21.5 min, p = 0.734) and perforation risk (p = 0.480) were similar between groups. The CKD group showed a tendency towards more bleeding events (p = 0.052) and had a significantly longer hospital stay (p = 0.001). In a subgroup analysis, stage 3 CKD patients exhibited a bleeding risk comparable to that exhibited by non-CKD patients (HR 1.35; 95% CI 0.36-5.06; p = 0.654), whereas stage 4 (HR 5.79; 95% CI 1.52-22.0; p = 0.010) and stage 5 (HR 4.80; 95% CI 1.58-14.6; p = 0.006) patients showed higher bleeding risks than non-CKD patients. In a multivariate analysis, stage 4/5 CKD was a significant predictor for bleeding risk (HR 4.99; 95% CI 1.32-18.8; p = 0.018). CONCLUSIONS: ESD for gastric epithelial neoplasms can be performed in stage 3 CKD patients with comparable efficacy and safety to that performed in non-CKD patients. Stage 4 and 5 CKD patients should be closely monitored for bleeding events after ESD.

Winged Partially Covered Self-Expandable Metal Stent to Prevent Distal Migration in Malignant Gastric Outlet Obstruction.

BACKGROUND: Through-the-scope implantation of self-expandable metal stents can be used for the palliation of malignant gastric outlet obstruction. Although covered stents were developed to prevent tumor ingrowth, often seen with uncovered stents, migration is still a major problem. Especially, surgical treatment is required for some patients if distal migration occurs. AIMS: To evaluate the usefulness of the newly designed winged stent that was developed to prevent distal stent migration. METHODS: This was a single-center, single-arm, retrospective study. A total of 63 inoperable cancer patients with symptomatic gastric outlet obstruction were reviewed to evaluate the safety and efficacy of a newly designed partially covered self-expandable metal stent with star-shaped wing flaps at the proximal end to reduce distal stent migration. RESULTS: Technical and clinical successes were achieved in 100% and 87.3% of patients, respectively. The gastric outlet obstruction scoring system score significantly improved after stent placement (from median 1 to 2, P < 0.001). The median duration of stent patency was 147 days (interquartile range 76-201), and median duration of overall survival was 176 days (interquartile range 79-325). Stent migration was observed in seven patients (11.1%), and restenosis was developed in 12 patients (19.0%). All cases of migration were proximal, and no distal migration was observed. Endoscopic removal of migrated stents was performed successfully in all cases. CONCLUSIONS: The newly designed winged stent showed feasible efficacy and safety for malignant gastric outlet obstruction. Furthermore, it effectively prevented distal stent migration.

Efficacy and safety of endoscopic submucosal dissection for gastric neoplasms in patients with compensated liver cirrhosis: a propensity score-matched case-control study.

BACKGROUND AND AIMS: The clinical outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms in liver cirrhosis patients have not been adequately reported, leading to clinician concerns about adverse events, including bleeding and the deterioration of liver function. We compared the efficacy and safety of ESD between cirrhosis and noncirrhosis patients. METHODS: Between January 2005 and December 2014, 158 cirrhosis patients underwent ESD for gastric neoplasms at a tertiary medical institution. Their clinical outcomes were compared with those of a propensity score-matched control group (158 patients) selected from noncirrhosis patients, using age, sex, histology, tumor location, and lesion size as variables. RESULTS: En bloc resection (96.8%), curative resection (89.9%), and adverse event (bleeding [10.1%] and perforation [1.9%]) rates in the cirrhosis group did not differ significantly from those in the noncirrhosis group. The median procedure time (25.0 vs 23.0 minutes) was also comparable between the groups. In a survival analysis cirrhosis patients exhibited a significantly higher mortality risk than noncirrhosis patients (hazard ratio [HR], 3.52; 95% confidence interval [CI], 1.35-9.23; P = .01). Cirrhosis patients without hepatocellular carcinoma (HCC) showed no statistically significant difference in mortality compared with the noncirrhosis group (HR, 2.14; 95% CI, .72-6.39; P = .171). Three of 153 patients (2%) exhibited a deterioration of prognosis from Child-Pugh class A to B. CONCLUSIONS: In compensated cirrhosis patients, especially those without HCC, ESD for gastric epithelial neoplasms can be performed with safety and efficacy comparable with that in noncirrhosis patients, without deterioration in liver function.

Immortalization of Porcine 11ß-Hydroxysteroid Dehydrogenase Type 1-Transgenic Liver Cells Using SV40 Large T Antigen.

Cortisol is a steroid hormone essential to the maintenance of homeostasis that is released in response to stress and low blood glucose concentration. Cortisol is converted from cortisone by 11ßhydroxysteroid dehydrogenase type 1 (HSD11B1). It has been reported that too much cortisol or overexpression of HSD11B1 induces obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue. In our previous study, HSD11B1-transgenic (TG) fibroblasts were established, and a porcine model was generated by SCNT using those fibroblasts. Hepatocytes overexpressing HSD11B1 were obtained from livers of this porcine model and cultured in vitro. However, the primary hepatocytes were found to have a short life span or low proliferation rate. To overcome these problems, the SV40 large T antigen was transduced into primary HSD11B1-TG hepatocytes, and those cells were immortalized. Immortalized HSD11B1-TG hepatocytes showed restored morphology, more rapid proliferation rate, and more expression of HSD11B1 than primary hepatocytes. As well, these cells kept the hepatic characteristics such as gluconeogenic response to cortisone and increased expression of hepatic makers. The immortalized HSD11B1-TG hepatocytes may be useful for studying traits and potential therapeutic drugs for treatment of metabolic disorders induced by overexpression of HSD11B1.

Advanced developmental toxicity test method based on embryoid body's area.

Embryonic stem cell test (EST) evaluates the embryotoxic potential of substances and measures the half inhibition in viability of mouse embryonic stem cells (ESCs), fibroblasts (3T3 cells) and in cardiac differentiation of ESC. In this study, we suggest the developmental toxicity test method (termed EBT) applying area of embryoid bodies (EBs) instead of cardiac differentiation of EST. In the assessment of 21 substances, EB area was logarithmically decreased in dose-dependent manner. Decline in EB area resulted in decrease of beating ratio during differentiation of ESCs. In classification by the EBT-based prediction model reflecting decline in cell viability and EB area, toxicity for 21 chemicals showed 90.5% accuracy. In the results of next generation sequencing, reduction in EB area resulted from cell cycle arrest mediated by HDAC2 and CDKN2A. Conclusively, EBT is advanced and is a useful tool to assess and classify various embryotoxicants in a short time with less effort.

Inhibitory effect of progesterone during early embryonic development: Suppression of myocardial differentiation and calcium-related transcriptome by progesterone in mESCs: Progesterone disturb cardiac differentiation of mESCs through lower cytosolic Ca(2.).

Progesterone (PG) and its derivates are used in prevention of spontaneous miscarriage. However, some studies have reported that exposure to PG and its derivates during pregnancy can cause malformations and affect both blood pressure and the cardiovascular system. The effect of PG on cardiomyogenesis of mouse embryonic stem cells (mESCs) is not well known. Expression of Pgr mRNA showed an opposite pattern of beating-ratio during differentiation. PG treatment resulted in reduction of the beating ratio to 60.45±1.54% from 92.17±2.98% in normal differentiation, reduced transcripts of heart morphogenesis and Ca(2+) binding-related genes in the next generation sequencing data and significantly decreased expression levels of Ca(2+)/contraction-related genes including Ryr2, Calm2, Trpv2, and Mylk3, the intracellular Ca(2+) level, and the beating frequency. These results suggest that PG exerts inhibitory effects on differentiation of mESCs into functional cardiomyocytes.

Clinical outcomes of endoscopic resection for gastric neoplasms in the pylorus.

BACKGROUND: Endoscopic resection for gastric neoplasms in the pylorus is a technically difficult procedure. We investigated clinical outcomes to determine the feasibility and effectiveness of endoscopic resection for gastric neoplasms in the pylorus. METHODS: Subjects who underwent endoscopic resection for gastric neoplasms in the pylorus between January 1997 and February 2012 were eligible. RESULTS: A total of 227 subjects underwent endoscopic resection for 228 gastric adenomas and early cancers in the pylorus. En bloc resection was achieved for 193 lesions (84.6%), including complete resection of 195 lesions (85.5%), and curative resection of 167 lesions (73.2%). Complete resection and curative resection rates were significantly different according to the location (prepyloric, pyloric, and postpyloric, P = 0.002 and P = 0.006). Delayed bleeding and stricture occurred in 5.3 and 3.1%, respectively, and there was no patient with perforation. During a median follow-up period of 79.0 months, local tumor recurrence was detected in 2.6%. CONCLUSIONS: Endoscopic resection appears to be a feasible and effective method for the treatment of pyloric neoplasms, regardless of the location and distribution of tumor. Thorough evaluation of the distal margin of the tumors is necessary when tumors involve or extend beyond the pyloric ring, and the appropriate use of additional techniques may be useful.

[Clinical usefulness of bile cytology obtained from biliary drainage tube for diagnosing cholangiocarcinoma].

BACKGROUND/AIMS: Biliary drainage is performed in many patients with cholangiocarcinoma (CCA) to relieve obstructive jaundice. For those who have undergone biliary drainage, bile cytology can be easily performed since the access is already achieved. This study aims to determine the clinical usefulness of bile cytology for the diagnosis of CCA and to evaluate factors affecting its diagnostic yield. METHODS: A total of 766 consecutive patients with CCA underwent bile cytology via endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage from January 2000 to June 2012. Data were collected by retrospectively reviewing the medical records. We evaluated the diagnostic yield of bile cytology with/without other sampling methods including brush cytology and endobiliary forcep biopsy, and the optimal number of repeated bile sampling. Several factors affecting diagnostic yield were then analyzed. RESULTS: The sensitivity of bile cytology, endobiliary forceps biopsy, and a combination of both sampling methods were 24.7% (189/766), 74.4% (259/348), and 77.9% (271/348), respectively. The cumulative positive rate of bile sampling increased from 40.7% (77/189) at first sampling to 93.1% (176/189) at third sampling. On multivariate analysis, factors associated with positive bile cytology were perihilar tumor location, intraductal growing tumor type, tumor extent ≥ 20 mm, poorly differentiated grade tumor, and three or more samplings. CONCLUSIONS: Although bile cytology itself has a low sensitivity in diagnosing CCA, it has an additive role when combined with endobiliary forceps biopsy. Due to the relative ease and low cost, bile cytology can be considered a reasonable complementary diagnostic tool for diagnosing CCA.

Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository.

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.