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Purpose: Endoscopic histoacryl injection (EHI) is reported to be an effective treatment modality for bleeding gastric varices (GVs) but controversial as a prophylactic treatment for non-bleeding GVs because efficacy and safety have yet to be determined. The aim of this study was to evaluate safety and long-term outcomes of prophylactic EHI for non-bleeding GVs with a high risk of bleeding.Methods: Thirty-three patients (23 males/10 females, mean age 56.6 years old) with a high risk of gastric variceal bleeding (large tumorous (27), red color sign (14) or rapidly growing in size (1)) underwent EHI. According to the grade of GVs, 25 patients belonged to F3, seven to F2, and one to F1. In terms of the locations of GVs, four patients belonged to type IGV1, 21 to type GOV2, and eight to type GOV1.Results: Obliteration of GVs was achieved in all of the treated patients. Twenty-three patients required one session and ten needed more than two sessions to obliterate their GVs. A mean volume of histoacryl used per session was 2.0 ml. Complications related to the procedure included immediate bleeding in two patients and bacteremia in one patient. The mean duration of follow-up was 12.2 months and eradication of GVs was achieved in 21 (95%) of 22 patients who were followed-up more than 3 months. Index GVs recurred in three of 21 patients (14%) and re-bleeding in index GVs after EHI occurred in two of 26 patients (8%).Conclusions: Prophylactic EHI can be a promising procedure for eradication of non-bleeding GVs in case with a high risk of bleeding. [ABSTRACT FROM AUTHOR]

SH2-containing protein tyrosine phosphatase 1 (SHP1) is an important negative regulator in cytokine-mediated signal transduction and cell cycling. Recent studies have demonstrated that SHP1 promoter methylation is frequently observed in gastric adenocarcinoma tissues. In this in vitro study, we attempted to reveal promoter hypermethylation and to investigate effects of SHP1 in gastric carcinoma cell lines. We observed that both gene and protein expression of SHP1 were negative in 8 of 10 gastric cancer cell lines (SNU-1, SNU-5, SNU-16, SNU-638, SNU-719, MKN-28, MKN-45, AGS). Methylation-specific PCR (MSP) showed a methylation-specific band only in the 10 gastric cancer lines. Bisulfite pyrosequencing in AGS, MKN-28, and SNU-719 cells indicated that methylation frequency was as high as 94.4, 92.6, and 94.5 %, respectively, in the three cell lines. Treatment of SNU-719, MKN-28, and AGS cells with 5-Aza-2'-deoxycytidine (5-Aza-dc) led to re-expression of SHP1 in these cells. Introduction of exogenous SHP1 in SNU-719 and MKN-28 cells by transient transfection substantially downregulated protein expression of constitutive phosphor-Janus kinase 2 (JAK2) (tyrosine 1007/1008) and phosphor-signal transducers and activators of transcription 3 (STAT3) (tyrosine 705), which in turn decreased expression of STAT3 target genes including those encoding cyclin D1, MMP-9, VEGF-1, and survivin. Induction of SHP1 significantly inhibited cell proliferation, migration and invasion in SNU-719 and MKN-28 cells. Taken together, epigenetic silencing of SHP1 is frequently caused by promoter hypermethylation in gastric carcinoma cells. Overexpression of SHP1 downregulates the JAK2/STAT3 pathway to modulate various target genes and inhibit cell proliferation, migration, and invasion in gastric cancer cells.

Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma (CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA (HL-CCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliary-enteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.

Aim: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models., Methods: Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW., Results: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α., Conclusion: PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.

Methylation rates of the Ras association domain family 1A gene (RASSF1A) have been variously reported as between 7.5 and 66.7% in gastric carcinoma tissues. The role of this gene in gastric cancer also remains to be fully elucidated. The present study aimed to investigate whether promoter hypermethylation of RASSF1A occurs in gastric adenocarcinoma tissues and gastric cancer cell lines, and to determine the effects of RASSF1A in gastric carcinoma cell lines. The results showed a methylation‑specific band only in SNU‑719, MKN28 and AGS human gastric cancer cells (indicating full methylation), none of which exhibited RASSF1A expression. By contrast, SNU‑16, MKN‑45 and KATO‑III human gastric carcinoma cells exhibited methylation as well as unmethylation‑specific bands (indicating partial methylation), and all displayed positive or weakly positive expression of RASSF1A. Bisulfite sequencing in AGS and SNU‑719 cells revealed that virtually all CpG sites were densely methylated. When SNU‑719, MKN‑28 and AGS cells were treated with the demethylating agent 5‑aza‑2'‑deoxycytidine, RASSF1A gene expression was restored and the methylation‑specific polymerase chain reaction pattern was altered in all three cell lines. Transfection of a plasmid expressing RASSF1A into AGS and SNU‑719 cells significantly inhibited cell proliferation. Exogenous RASSF1A also reduced the expression of cyclin D1 and phospho‑retinoblastoma protein, and increased that of p27 as demonstrated by western blot analysis. Furthermore, RASSF1A expression was significantly reduced (P=0.048) and the methylation rate was elevated in gastric adenocarcinoma tissues, compared with those in adjacent healthy intestinal metaplasia (34.6 vs. 66.7%, P=0.029). The present study indicated that epigenetic silencing of RASSF1A is frequently caused by promoter hypermethylation in gastric cancer cell lines as well as in gastric adenocarcinoma tissues, which may contribute to gastric carcinogenesis.

Aim: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9 (MMP-9), and colitis in interleukin (IL)-10(-/-) mice., Methods: To synchronize colitis, 8- to 10-wk-old IL-10(-/-) mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein (1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expressions were analyzed in IL-10(-/-) mice and in Colo 205 cells., Results: Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon (IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines (IL-17A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for pSTAT3 and MMP-9 was significantly decreased in the butein-treated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells., Conclusion: Butein ameliorated colitis in IL-10(-/-) mice by regulating IL-6/STAT3 and MMP-9 activation.

Intestinal lymphangiectasia is a rare disease characterized by focal or diffuse dilated enteric lymphatics with impaired lymph drainage. It causes protein-losing enteropathy and may lead to gastrointestinal bleeding. Commonly, lymphangiectasia presents as whitish spots or specks. To our knowledge, small bowel bleeding resulting from polypoid intestinal lymphangiectasia has not been reported. Here, we report a rare case of active bleeding from the small bowel caused by polypoid lymphangiectasia with a review of the relevant literature. An 80-year-old woman was hospitalized for melena. Esophagogastroduodenoscopy could not identify the source of bleeding. Subsequent colonoscopy showed fresh bloody material gushing from the small bowel. An abdominal-pelvic contrast-enhanced computed tomography scan did not reveal any abnormal findings. Video capsule endoscopy showed evidence of active and recent bleeding in the ileum. To localize the bleeding site, we performed double balloon enteroscopy by the anal approach. A small, bleeding, polypoid lesion was found in the distal ileum and was successfully removed using endoscopic snare electrocautery., (© 2013 Baishideng Publishing Group Co., Limited. All rights reserved.)

Objective: This study was aimed to evaluate the prevalence of eosinophilic esophagitis (EoE) among patients with esophageal or upper gastrointestinal (UGI) symptoms., Methods: Patients with esophageal or UGI symptoms including dysphagia food impaction, acid regurgitation, heartburn, chest pain, epigastric pain, nausea and/or vomiting were prospectively collected. The enrolled patients responded to a symptomatic questionnaire and underwent an esophagogastroduodenoscopy and esophageal biopsies. Supportive endoscopic findings of EoE (ring-like appearance, liner furrows, whitish papules, shearing or friability) were recorded. EoE was diagnosed if patients had chronic UGI or esophageal symptoms, the esophageal biopsy showed ≥15 eosinophils/high-power field and were unresponsive to 2-3 weeks of proton pump inhibitors., Results: A total of 122 patients were enrolled and supportive endoscopic findings were found in 31 (25.4%) patients [whitish papules: 19 (15.6%), ring-like appearance: 8 (6.6%), linear furrows: 5 (4.1%)]. One patient had a simultaneous ring-like appearance and linear furrows. EoE was diagnosed in 8 (6.6%) patients and supportive endoscopic findings and past history of gastroesophageal reflux disease, allergic rhinitis and atopic dermatitis were more common in EoE positive than EoE negative patients. The diagnostic yield of endoscopic findings was 40.0% (2/5) in linear furrows, 25.0% (2/8) in ring-like appearance and 15.8% (3/19) in whitish papules., Conclusion: Prevalence of EoE among patients with esophageal or UGI symptoms was 6.6%. Linear furrows and ring-like appearance had a relatively high diagnostic value., (© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)

Purpose: Endoscopic histoacryl injection (EHI) is reported to be an effective treatment modality for bleeding gastric varices (GVs) but controversial as a prophylactic treatment for non-bleeding GVs because efficacy and safety have yet to be determined. The aim of this study was to evaluate safety and long-term outcomes of prophylactic EHI for non-bleeding GVs with a high risk of bleeding., Methods: Thirty-three patients (23 males/10 females, mean age 56.6 years old) with a high risk of gastric variceal bleeding (large tumorous (27), red color sign (14) or rapidly growing in size (1)) underwent EHI. According to the grade of GVs, 25 patients belonged to F3, seven to F2, and one to F1. In terms of the locations of GVs, four patients belonged to type IGV1, 21 to type GOV2, and eight to type GOV1., Results: Obliteration of GVs was achieved in all of the treated patients. Twenty-three patients required one session and ten needed more than two sessions to obliterate their GVs. A mean volume of histoacryl used per session was 2.0 ml. Complications related to the procedure included immediate bleeding in two patients and bacteremia in one patient. The mean duration of follow-up was 12.2 months and eradication of GVs was achieved in 21 (95%) of 22 patients who were followed-up more than 3 months. Index GVs recurred in three of 21 patients (14%) and re-bleeding in index GVs after EHI occurred in two of 26 patients (8%)., Conclusions: Prophylactic EHI can be a promising procedure for eradication of non-bleeding GVs in case with a high risk of bleeding.

Background: Sphingolipids play a very important role in cell membrane formation, signal transduction and plasma lipoprotein metabolism. The first rate-limiting step in the sphingolipid biosynthetic pathway is catalyzed by serine palmitoyltransferase (SPT), and myriocin is a potent and specific inhibitor of SPT. We investigated the impact of SPT inhibition on cholesterol gallstone formation in C57BL/6J mice., Methods: Three groups of eight-week-old C57BL/6J mice were utilized. Each group consisted of 20 mice; group A, B, and C were fed normal chow, lithogenic diet with phosphate buffered saline, and lithogenic diet with myriocin (0.3 mg/kg), respectively, for 6 weeks. The ceramide levels in both serum and bile were assessed by high performance liquid chromatography analysis. Protein expression of ERK, JNK and p38 in the extracted gallbladder were determined by Western-blot analysis., Results: Myriocin treatment caused a significant decrease in the rate of cholesterol gallstone formation. The lithogenic diet mice (group B) showed the highest ceramide activities in both the serum and bile among all the tested groups and there was significant suppression of the ceramide levels in both the serum and bile of the myriocin-treated mice (group C, p < 0.05). Phosphorylation of p38 in the gallbladder was increased in the lithogenic-diet mice and the expression of phosphorylated p38 was significantly suppressed in the myriocin treated mice., Conclusions: SPT inhibition by myriocin suppressed gallstone formation and the levels of ceramide in both the serum and bile. p38 in the cellular signaling pathways might be associated with cholesterol gallstone formation.

Melanosis or pseudomelanosis of the gastrointestinal tract refers to an accumulation of pigment deposits in the gastrointestinal mucosa. Pigmentation can affect the entire gastrointestinal tract. Melanosis of the colon is not uncommon, but black pigmentation of the small intestine is extremely rare. We report a case of pseudomelanosis of the terminal ileum in a 52-year-old woman who had ingested a tablespoon of charcoal powder daily for 2 years. Numerous small and medium-sized irregular grayish black pigmentations mostly on the background of geographic light grayish discolored mucosa and some on the normal-looking mucosa were seen on the terminal ileum. The finding was similar to a cut surface of a dragon fruit and we named the lesion 'dragon fruit ileum'. Follow up endoscopy 10 months later revealed no significant change in the pigmentation. We could not search any English literature on this lesion. However, we could find three cases from two papers from Korea describing similar lesions after chronic charcoal ingestion and the papers were reviewed with a report of our case.

Cholesterol and sphingolipids are major lipid constituents of the plasma membrane and have been implicated in a number of human diseases, such as atherosclerosis, fatty liver, diabetes mellitus, coronary heart disease, and hypertension. However, the relationship between cholesterol and sphingolipid metabolism has not been investigated. The purpose of this study was to determine whether dietary cholesterol would induce the alteration of sphingolipid metabolism in hamsters. Hypercholesterolemia was induced in hamsters by placing them on an experimental diet containing 0.5% cholesterol plus 0.5% choline chloride for 8 and 12 weeks. The serum profile of the hamsters showed that the administration of cholesterol increased the levels of total cholesterol, LDL cholesterol, and triglycerides as well as the activities of GOT and GPT. The levels of ceramide and sphingosine-1-phosphate (So-1-P) were remarkably elevated by 6-fold, respectively, in the bile juice of cholesterol-fed hamsters. Interestingly, the levels of iNOS and GFAP were increased in the gallbladders of cholesterol-fed hamsters. In addition, the immunostaining of pSTAT3 was increased on the gallbladder epithelium after cholesterol feeding. These results suggest that sphingolipid metabolism may be regulated in the bile juice during cholesterol feeding and may be a potential target for the treatment of hypercholesterolemia-induced diseases.

Background/aims: For hypopharyngeal tumors, surgical therapy under general anesthesia is the mainstay of treatment; however, the endoscopic treatment of benign hypopharyngeal tumors has not been fully evaluated for its feasibility and safety. We determined the technical feasibility and safety of endoscopic treatment for benign hypopharyngeal tumors., Methodology: A total of 22 patients (15 men, 7 women) with benign hypopharyngeal tumors underwent endoscopic resection. All tumors were treated using one of two endoscopic mucosal resection (EMR) techniques: the injection and cut method for the polypoid lesions (6 cases) or EMR using a cap (EMR-C) for the flat or protruding lesions with wide bases (16 cases)., Results: In all 22 patients, the most common findings detected during routine GI endoscopy were lymphoepithelial cysts (11 cases) followed by papillomas (5 cases). All benign hypopharyngeal tumors were successfully removed by endoscopic resection without sedation. There were no major procedure-induced complications. Minor complications occurred in 3 patients and included minimal bleeding (n=1), pain (n=1) and low-grade fever (n=1)., Conclusions: As a treatment modality for benign hypopharyngeal tumors, endoscopic resection is a simple, less invasive, safe, and likely cost-effective method. Endoscopic resection should be considered an alternative to surgical therapy in appropriately selected patients.

Background/aims: Severe acute pancreatitis occurs in about 20% of the patients with acute pancreatitis and can be associated with multiorgan failure and local complications. In patients with predicted severe acute pancreatitis, overall mortality rates are about 15-30%. The aim of this study was to determine the factors correlated with mortality in patients with severe acute pancreatitis., Methods: We reviewed five hundread and seventy two consecutive cases of acute pancreatitis from January, 2000 to December, 2005. Of them, 109 patients who fulfilled the criteria of Atlanta classification for severe acute pancreatitis were enrolled. Data were collected by chart reviews including age, gender, etiology, body mass index (BMI), modified Glasgow score, APACHE II score, APACHE III score, Balthazar CT index, and other laboratory parameters performed within 48 hours after the initial admission., Results: Severe acute pancreatitis was most commonly caused by alcohol. Overall mortality rate was 20.2% in severe acute pancreatitis and 10 (45%) deaths occurred within the first week. Multiple logistic regression analysis identified serum creatinine, corrected calcium concentrations, and CT index as predictors of mortality in patients with severe acute pancreatitis. The risk score (R) was calculated by combining 3 prognostic values with regression coefficients; R=2.512 loge (creatinine mg/dL)+1.729 loge (CT index)??4.780 loge (corrected calcium mg/dL). The AUC for this score was 0.877 and a cutoff level of 0 was determined to predict the mortality with 83.3% sensitivity and 89.5% specificity., Conclusions: The newly designed risk score comprising 3 parameters can be used as the significant early predictor for hospital mortality in severe acute pancreatitis.

Primary small cell carcinoma (SCC) of stomach is a rare and highly aggressive malignancy with extremely poor prognosis. We report a 71-year-old man with upper abdominal pain diagnosed as single hepatic metastasis of SCC from mixed SCC and adenocarcinoma of the stomach. An endoscopic examination showed the presence of Borrmann type 2 gastric cancer, 2 cm in size on the lesser curvature of antrum. An abdominal CT scan revealed a huge dumbbell shaped mass with peripheral arterial enhancement and central low density in left lobe of the liver. Endoscopic biopsies showed solid proliferation of small, monotonous tumor cells with hyperchromatic nuclei and scanty cytoplasm. The neoplastic cells were positive for immunostaining with anti-chromogranin and anti-synaptophysin. There were also other neoplastic cells with gland formation being positive for anti- cytokeratin. On the basis of these findings, we made a final diagnosis of mixed SCC and adenocarcinoma of the stomach. In addition, we also confirmed hepatic metastasis of SCC through the microscopic finding and immunostaining of tissues of liver mass. Conclusively, we report a case of hepatic metastasis of SCC only from mixed SCC adenocarcinoma of the stomach.

Background/aims: MELD-Na (model for end-stage liver disease with incorporation of serum sodium) was suggested to provide better survival prediction than MELD alone for patients with end stage liver disease. However, there is no data verifying the usefulness of MELD-Na for predicting short term mortality of cirrhotic patients in Korea. This study was aimed to determine whether MELD-Na would be more accurate in predicting short term mortality than other scoring systems such as Child-Turcotte-Pugh (CTP) or MELD., Methods: Data from 355 patients admitted due to liver cirrhosis were retrospectively reviewed. The cumulative survival rates were obtained. Prediction of mortality rate for three months and one year were analyzed using the area under the receiver's operating characteristics curve (AUC)., Results: One hundred patients (28%) died during the study period. All of the three systems showed significant differences in the cumulative survival rate according to the scores on admission (p0.001). The AUC of CTP, MELD, and MELD-Na in predicting three-months mortality were 0.828, 0.845, and 0.862 (p0.05), and the AUC of each score system for death within one year were 0.792, 0.800, and 0.831, respectively (p0.05). The AUC of MELD-Na in predicting short term death were the highest, although it was not statistically significant. Multivariate analysis showed that only MELD-Na was significantly related to three-month mortality (p=0.012)., Conclusions: MELD-Na is more appropriate in predicting short term mortality, but larger scale studies are needed to confirm the superiority of MELD-Na to MELD and CTP in patients with liver cirrhosis.

Benign neoplasia of the duodenum are very rare. Moreover, duodenal tubulovillous adenomas are more uncommon lesions. The microscopic structure of tubulovillous adenoma has frond-like projection of mucosa with branching papillary structure and generally upward growth into the lumen. We describe a 72-year-old man who showed aduodenal tubulovillous adenoma with unusual inverted cystic growth pattern. Interestingly, this tubulovillous adenomatous lesion was interrupted by gastric metaplasia in the deep portion of the cyst and was closely surrounded by Brunner's glands. Although histogenesis of gastric metaplasia of duodenum is not fully understood, Brunner's glands has been suggested as a precursor for gastric metaplasia. Therefore, these findings argued that this adenoma arises from Brunner's glands through gastric metaplasia. This is the first case of inverted cystic tubulovillous adenoma involving Brunner's glands of duodenum with gastric metaplasia.

Background/aims: Capsule endoscopy (CE) has become a valuable modality for the detection of small bowel lesions. The usefulness of CE for obscure gastrointestinal (GI) bleeding has been established with an overall diagnostic yield of 60%. It is unknown whether CE is of equal value in all the patients or of greater benefit in selected groups in Korea. We evaluated the factors that affect the diagnostic yields of CE in patients with obscure GI bleeding., Methods: CE was performed in 126 consecutive patients [74 men and 52 women mean age 52.5 years (25-75 yrs), 23 with active bleeding] with obscure GI bleeding between September 2002 and July 2004. Patients were divided into two groups: those with documented bleeding lesions and those with non specific CE findings. We analyzed the clinical characteristics and other parameters that influenced the diagnostic yields of CE., Results: A definite or probable cause for obscure GI bleeding was found in 69% (80/116) of the patients. NSAID induced ulcer (16.4%) and angiodysplasia (12.1%) were the most common diagnoses. In patients with active bleeding, the diagnostic yield was significantly greater than that of the patients with occult bleeding (80% vs. 68.3%, p<0.05). However, there was no significant difference in parameters between patients with abnormal CE and those with normal CE in respect to gender, age, previous bleeding history, need for transfusion, cecum imaging, and bowel preparation., Conclusions: The diagnostic yield of CE in patients with obscure GI bleeding is 69%. It is significantly higher in patients with active bleeding.