Journal of Gastroenterology and Hepatology (J Gastroenterol Hepatol)

Publications in this journal

• Article: Review Article:Venous and Arterial Disease in Inflammatory Bowel Disease.

  Victoria P Tan, Alvin Chung, Bryan P Yan, Peter R Gibson
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  ABSTRACT: Awareness is increasing that risk of venous thrombo-embolism and development of atherosclerosis is elevated in patients with some chronic inflammatory diseases. This review aimed to examine the risk of vascular disease in patients with inflammatory bowel disease (IBD) and to identify potential pathogenic mechanisms and therapeutic approaches. An extensive literature search was conducted using MEDLINE database, Cochrane Library and international conference abstracts for studies pertaining to venous and arterial thromboembolism in adult IBD patients. There is a 1.1-3.6 fold risk of venothromboembolism in IBD, affecting 0.55%-6.15% of patients. Risks are increased during a flare or with chronically active inflammation. Evidence is building that there may be a modestly increased risk of arterial disease overall, despite evidence that traditional risk factors may be reduced. Multiple pathogenic factors have been identified including endothelial dysfunction, inflammation-mediated calcium deposition in the media of arteries, hyperhomocysteinaemia, platelet activation, and altered coagulation and fibrinolysis. The key to active and preventive therapy is to effectively treat inflammation. Recommendations for prophylaxis of venothromboembolism have followed guidelines where they exist and have been extrapolated from studies of other at-risk conditions, as have those for arterial disease, where screening for risk factors and actively treating abnormalities is encouraged. In conclusion, patients with IBD are at considerably increased risk of venothromboembolism and probably of arterial disease, in particular mesenteric ischaemia and ischaemic heart disease. Increased penetration of gaps between this knowledge and clinical therapeutic action to prevent thromboembolic events into IBD clinical practice is needed.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Expression of metallothionein-1 and metallothionein-2 as a prognostic marker in hepatocellular carcinoma.

  Yangsoon Park, Eunsil Yu
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  ABSTRACT: BACKGROUND AND AIMS: Metallothioneins (MTs) -1 and -2 are a group of low-molecular weight, cysteine-rich, intracellular metal binding proteins that are involved in diverse functions such as metal homeostasis, cell cycle progression, cell differentiation and carcinogenesis. This study investigated the expression of MT-1 and MT-2 as a prognostic marker in hepatocellular carcinoma (HCC). METHODS: A total of 370 HCCs, 336 adjacent non-cancerous livers, and 12 normal livers were evaluated for the expression of MT-1 and MT-2 by immunohistochemical staining on tissue microarray. The relationship between the expression of MT-1 and MT-2 and the clinicopathological parameters of HCC was assessed. RESULTS: The expression of MT-1 and MT-2 was uniformly strong in nucleus and cytoplasm in normal liver, whereas it was variable in non-cancerous livers and HCCs. The loss of nuclear and cytoplasmic expression of MT-1 and MT-2 was significantly frequent in HCCs compared with the adjacent noncancerous livers (p < 0.001). The loss of nuclear expression of MT-1 and MT-2 was significantly correlated with high Edmondson-Steiner grade and the presence of microscopic vascular invasion (p < 0.05). In multivariate analysis, the loss of nuclear MT-1 and MT-2 expression was identified as an independent poor prognostic factor for both recurrence free survival and overall survival. CONCLUSIONS: The expression of MT-1 and MT-2 may play a role in differentiation and carcinogenesis, and can be used as a useful predictor of prognosis in HCC.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Outcome of endoscopic therapy for cancer bleeding in patients with unresectable gastric cancer.

  Young-Il Kim, Il Ju Choi, Soo-Jeong Cho, Jong Yeul Lee, Chan Gyoo Kim, Mi-Jung Kim, Keun Won Ryu, Young-Woo Kim, Young Iee Park
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  ABSTRACT: BACKGROUND AND AIM: Gastric cancer bleeding is not rare complication in patients with advanced gastric cancer (AGC). The aim of this study was to evaluate the efficacy and clinical outcomes of endoscopic therapy (ET) for upper gastrointestinal bleeding (UGIB) from unresectable AGC. METHODS: Data from 113 patients with UGIB from unresectable AGC who underwent ET at the National Cancer Center, Korea were analyzed retrospectively. Success rates of endoscopic hemostasis, rebleeding rates, mortality at 30 days, and overall survival (OS) rate after initial hemostasis were investigated. RESULTS: The initial hemostasis rate was 92.9% (105/113). Electrocoagulation was the most common method used (92.0%, 104/113) and combination ET was required in 34 patients (30.1%). Rebleeding occurred in 43 patients (41.0%); 3-day and 30-day rebleeding rates were 18.1% and 29.5%, respectively. Multivariate logistic regression analysis showed that transfusion of packed red blood cells (>5 units) was associated with early rebleeding (≤3 days after initial hemostasis) (odd ratio, 4.75; 95% confidential interval, 1.45-15.57; P=0.010). ET was attempted in 18 patients with rebleeding; hemostasis was achieved in 88.9%. The 30-day mortality rate after initial bleeding event was 15.9%. Median OS after initial hemostasis was 3.2 months. OS was lower for patients with early rebleeding than for those with late rebleeding (>3 days after initial hemostasis) or without rebleeding (1.0, 3.1, and 4.3 months, respectively; P=0.004). CONCLUSIONS: ET, primarily endoscopic electrocoagulation, achieved a high initial hemostasis rate for UGIB in patients with unresectable AGC. However, rebleeding frequently occurred and early rebleeding was associated with poor survival.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Continuous imaging of esophago-gastric junction in patients with reflux esophagitis using 320-row area detector CT: a feasibility study.

  Kousuke Fukazawa, Kenji Furuta, Kyoichi Adachi, Shino Shimura, Kazutoshi Kamiyama, Masahito Aimi, Shunji Ohara, Takafumi Kajitani, Masakatsu Tsurusaki, Hajime Kitagaki, Yoshikazu Kinoshita
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  ABSTRACT: BACKGROUND AND AIM: The function of the lower esophageal sphincter (LES) is evaluated using an esophageal manometric study. However, information regarding the surrounding organs is difficult to obtain with use of a sensor catheter. We investigated the utility of 320-row area detector computed tomography (CT) to evaluate morphological changes of the esophago-gastric junction and surrounding organs. METHODS: The study subjects were 18 healthy volunteers and 29 patients with reflux esophagitis (RE). Immediately after swallowing a diluted contrast agent, continuous imaging of the esophago-gastric junctional area was performed for 15 seconds. Using CT images, the presence or absence of esophageal hiatal hernia, His angle before and after swallowing, size of the diaphragmatic hiatus, morphologically identified-LES (MI-LES) length, intra-luminal horizontal area of MI-LES during relaxation phase, MI-LES thickness, abdominal esophagus length, subcutaneous fat area, visceral fat area, and esophago-gastric junction fat area were evaluated. RESULTS: Analysis of CT images showed more frequent occurrence of hiatal hernia, greater His angle, and a larger diaphragmatic hiatus in patients with severe RE, while the lengths of MI-LES and abdominal esophagus were shorter in those patients. Visceral and esophago-gastric junction fat areas tended to be greater in patients with RE. In all subjects, the posterior wall of the MI-LES was thicker than the anterior wall. CONCLUSION: Continuous imaging with 320-row area detector CT is useful to evaluate morphological changes in the esophago-gastric junction area in both normal individuals and patients with reflux esophagitis.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Comparison of clinical effectiveness of the emergent colonoscopy in patients with hematochezia according to the type of bowel preparation.

  Dae Seop Lim, Hyun Gun Kim, Seong Ran Jeon, Kwang Yeun Shim, Tae Hee Lee, Jin-Oh Kim, Bong Min Ko, Joo Young Cho, Joon Seong Lee
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  ABSTRACT: BACKGROUND/AIMS: Colonoscopy (CFS) is a valuable diagnostic tool in patients with hematochezia. However, the optimal preparation method of emergent CFS for hematochezia has not been defined. We investigated the clinical effectiveness of bowel preparation of patients with hematochezia using polyethylene glycol (PEG) solution and glycerin or water enemas. METHODS: The medical records of the past 7 years were reviewed. Patients presenting with hematochezia that occurred within the 24 h before admission were eligible for the study. All patients underwent CFS within 24 h after visiting the ER for hematochezia. Patients were classified into two groups according to the preparation method used (enema vs. PEG). RESULTS: Overall, 194 patients (125 enema vs. 69 PEG) were enrolled. The diagnostic rate of bleeding focus was lower in the enema group than in the PEG group (84% vs. 97.1%, p=0.008). Performance of endoscopic hemostasis at the initial CFS was more frequent in the enema group than the PEG group (40.8% vs. 10.1%, p<0.001). The rate of repeated CFS was higher in the enema group than the PEG group (44.0% vs. 18.8%, p<0.001). Postpolypectomy bleeding (PPB, n=33) was diagnosed during the initial study and was treated endoscopically. In cases of PPB, CFS (93.9%) was performed after an enema in all but two cases. CONCLUSIONS: In hematochezia patients, the PEG group showed a higher diagnostic rate and lower rate of repeated CFS. However, emergent colonoscopy after an enema only seems to be useful in patients with severe hematochezia or if the bleeding focus can be presumed.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: N-(3', 4'-dimethoxycinnamonyl) Anthranilic Acid Alleviated Experimental Colitis by Inhibiting Autoimmune Response and Inducing CD4(+) CD25(+) Regulatory T cells Production.

  Quan Wen, Liping Zhou, Huan Chen, Yan Zhang
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  ABSTRACT: BACKGROUND: Crohn's disease treatments available today are not quite satisfactory. N-(3', 4'-dimethoxycinnamonyl) anthranilic acid (3, 4-DAA) has been proved to be effective in many autoimmune diseases. Therefore, we investigated the immunologic function of 3, 4-DAA on trinitrobenzene sulfonic acid (TNBS) colitis and human Crohn's disease. METHODS: Mice with TNBS-induced colitis were treated with 3, 4-DAA or 1-methyl-tryptophan (1- MT). Colitis severity was assessed with clinical and histological scores. Cell proliferation, cytokine expression, and the percentage of CD4(+) CD25(+) T cells were measured in both mice and human samples. RESULTS: In mice treated with 3, 4-DAA, the clinical and histological scores were decreased (P<0.05); the proliferation of mesenteric lymph nodes (MLNs) cells and lamina propria mononuclear cells (LPMCs) were inhibited (P<0.05); Th1 cytokine expressions were decreased (P <0.05), and Th2 cytokine levels were increased (P<0.05). 3, 4-DAA also induced CD4(+) CD25(+) T cells expression (5.88±2.1 vs 11.03±2.93, P<0.05) in mice MLNs. Transfer of these cells into TNBS colitis mice resulted in the reduction of the disease activity index (DAI) and histological scores. In LPMCs isolated from human Crohn's disease, 3, 4-DAA had the same effect. It can inhibit the cell proliferation, decrease Th1 cytokine expressions (P <0.05), and increase Th2 cytokine levels (P<0.05). The percentage of CD4(+) CD25(+) T cells were also increased (1.60±0.14 vs 2.45±0.50, P<0.05). 1-MT treatment led to opposite outcomes. CONCLUSION: 3, 4-DAA can alleviate the severity of colitis through inhibiting Th1 cells response, promoting Th2 cytokines expression and inducing CD4(+) CD25(+) T cells expression.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Feasibility of Sentinel Node Navigation Surgery after Non-curative Endoscopic Resection for Early Gastric Cancer.

  Takaaki Arigami, Yoshikazu Uenosono, Shigehiro Yanagita, Daisuke Matsushita, Hideo Arima, Munetsugu Hirata, Yasuto Uchikado, Akihiro Nakajo, Hiroshi Okumura, Sumiya Ishigami, Shuichi Hokita, Shoji Natsugoe
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  ABSTRACT: BACKGROUND AND AIM: Recently, the use of additional surgery after non-curative endoscopic resection has gradually increased due to the rapid spread of endoscopic treatments in selected patients with early gastric cancer. Sentinel node navigation surgery (SNNS) has also been recognized as a minimally invasive surgery with personalized lymphadenectomy in early gastric cancer. Here, we assessed the feasibility of SNNS after non-curative endoscopic resection for early gastric cancer. METHODS: Sixteen patients with early gastric cancer, in whom additional surgery had been indicated due to non-curative endoscopic resection, were enrolled. They underwent a gastrectomy with standard lymphadenectomy. One day before surgery, (99m) technetium-tin colloid was endoscopically injected into the submucosa around the tumor. After surgery, the uptake of radioisotope in dissected lymph nodes was measured using Navigator GPS. Then, all dissected lymph nodes were investigated by hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) using an anti-human cytokeratin monoclonal antibody. RESULTS: HE staining demonstrated lymph node metastasis in 2 (12.5%) of 16 patients and in 3 (0.8%) of 382 nodes. However, IHC showed that none of the patients had lymph node micrometastasis. Sentinel nodes (SNs) were identified in all patients. The mean number of SNs was 3.1 (range, 1-6). Among 2 patients with lymph node metastasis, the SNs, at least, contained positive nodes. Accordingly, the false-negative and accuracy rates were 0% and 100%, respectively. CONCLUSION: Our results indicate that SNNS may have potential as a further minimally invasive surgery in early gastric cancer patients after non-curative endoscopic resection.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Expression of genes for miRNAs-processing enzymes is altered in advanced non-alcoholic fatty liver disease (NAFLD).

  H Sharma, M Estep, A Birerdinc, A Afendy, A Moazzez, H Elariny, Z Goodman, V Chandhoke, A Baranova, Zm Younossi
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  ABSTRACT: BACKGROUND AND AIM: Recently, microRNAs (miRNA) have been linked to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH). First transcribed as pri-miRNA, these molecules are further processed by a complex of endonuclear and cytosolic RNA binding molecules to form mature miRNAs. The aim of this study is to investigate mechanisms of miRNA regulation in the visceral adipose of obese NAFLD patients via measuring expression of miRNA processing enzymes and pri-miRNA. METHODS: Total RNAs were extracted from visceral adipose tissue (VAT) samples collected from patients undergoing bariatric surgery. All patients had biopsy-proven NAFLD [NASH patients (n = 12) and non-NASH NAFLD (n = 12)]. For each patient, we profiled mRNA levels for three miRNA processing elements (Drosha, DGCR8, and Dicer1) and seven pri-miRNAs (pri-miR-125b-2, pri-miR-16-2, pri-miR-26a-1, pri-miR-26a-2, pri-miR-7-1, pri-miR-7-2, and pri-miR-7-3). RESULTS: Expression of Dicer1, DROSHA and DGCR8 was significantly increased within the NASH cohort along with expression of pri-miR-7-1. The presence of focal necrosis on the liver biopsy correlated significantly with levels of Dicer1 and DGRC8. Both NASH and ballooning degeneration of hepatocytes correlated negatively with the expression levels of hsa-miR-125b. Histologic NASH correlated positively with the expression levels of pri-miR-16-2 and pri-miR-7-1. The presence of the hepatocyte's ballooning degeneration in the liver biopsy correlated positively with pri-miR-26a-1 and pri-miR-7-1. The expression profile of pri-miR-125b-2 also correlated positively with body mass index (BMI). CONCLUSIONS: Our findings support the hypothesis that VAT-derived miRNA may contribute to the pathogenesis of NASH in obese patients.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Addition of Thiopurines Can Recapture Response in Patients with Crohn's Disease who Have Lost Response to Anti-Tnf Monotherapy.

  David Eh Ong, Michael A Kamm, Juanda Leo Hartono, Mark Lust
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  ABSTRACT: BACKGROUND: Anti-tumour necrosis factor (TNF) antibodies are effective in maintaining remission in Crohn's disease. However a significant proportion of patients lose response to these agents with time. This study aimed to determine whether the introduction of a thiopurine in patients who have lost response to anti-TNF monotherapy results in regained response. METHODS: Five patients (four males; aged 22-38 years) with active Crohn's disease, who had an initial response to anti-TNF therapy but had lost response, were commenced on azathioprine or mercaptopurine at standard doses while continuing anti-TNF therapy. All had previously failed thiopurine therapy prior to starting anti-TNF treatment. RESULTS: All patients experienced improved clinical symptoms within two to six months, with benefit sustained over a mean follow-up of 19 months. Two patients with an elevated CRP at the time of thiopurine addition demonstrated a fall in CRP. Colonoscopy before and after thiopurine addition in four patients showed improvement in all, with mucosal healing achieved in two. No adverse effects of treatment were noted. CONCLUSIONS: Addition of a thiopurine in patients who have lost response to anti-TNF monotherapy is an effective strategy to recapture response, even if the patient has previously failed thiopurine therapy. Thiopurines may reduce immunogenicity or act synergistically with anti-TNF therapy.
  Journal of Gastroenterology and Hepatology 05/2013;
• Article: Genetics of inflammatory bowel disease: The state of play.

  Juleen A Cavanaugh
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):759-60.
• Article: Hepatobiliary and Pancreatic: Radiofrequency ablation for caudate lobe hemangioma.

  Xiaowu Zhang, Jiayin Yang, Lunan Yan
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):765.
• Article: Gastrointestinal: Schistosomiasis-Diagnosis by colonoscopy.

  Dm Gray, M Nakashima, No Davidson
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):763.
• Article: NX-PVKA assay, a conventional but refined prognostic biomarker for hepatocellular carcinoma.

  Naoya Sakamoto
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):755-6.
• Article: Heme oxygenase-1 and platelets in hepatic ischemia reperfusion injury.

  Benjamin L Woolbright, Hartmut Jaeschke
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):756-7.
• Article: Gastrointestinal: Colon cancer with cutaneous infiltration.

  Cr Achanta, D Dahiya, M Garg, Ss Rana, A Behera
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):762.
• Article: The more the merrier: Faecalibacterium prausnitzii in Crohn's disease.

  Claire L O'Brien, Gwen E Allison, Paul Pavli
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):757-9.
• Article: Gastrointestinal: Symptomatic bronchial aspiration of capsule endoscope - a significant complication.

  Ns Ding, C Hair, P De Cruz, J Watson
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):761.
• Article: Hepatobiliary and Pancreatic: Huge bile duct stones after hepaticojejunostomy.

  D Hashimoto, A Chikamoto, M Hirota, T Beppu, H Baba
  Journal of Gastroenterology and Hepatology 05/2013; 28(5):764.
• Article: Two-week Schedule of Hypofractionated Radiotherapy as a Local Salvage Treatment for Small Hepatocellular Carcinoma.

  Jin-Hong Park, Sang Min Yoon, Young-Suk Lim, So Yeon Kim, Ju Hyun Shim, Kang Mo Kim, Han Chu Lee, Byungchul Cho, Geumju Park, Jong Hoon Kim
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  ABSTRACT: BACKGROUND AND AIM: In cases of small hepatocellular carcinoma (HCC) where established curative treatment cannot be applied, stereotactic body radiotherapy (SBRT) has been used as a non-invasive alternative treatment modality. However, short-course SBRT may not be safe if the tumor is located around a critical normal organ. Therefore, we applied hypofractionated radiotherapy for these tumors, and evaluated outcomes of this treatment. METHODS: Between December 2008 and August 2011, 26 patients (28 lesions) with HCC were treated with hypofractionated radiotherapy. Inclusion criteria were HCC not suitable for surgery or other local ablative therapy, a tumor size < 6 cm, adequate hepatic function, a HCC located within 2 cm of a critical organ, and no evidence of vascular invasion. A dose of 4-5 Gy per fraction was given, with a total dose of 40-50 Gy over two weeks. RESULTS: The overall response rate was 67.9%, with 7 complete responses (25.0%) and 12 partial responses (42.9%) at 3 months after radiotherapy. The overall survival rates at 1 and 2 years were 88.5% and 67.2%, respectively. The local control rate at 2 years was 87.6%. The Intrahepatic recurrence-free and distant failure-free survival rates at 2 years were 36.5% and 68.2%, respectively. Grade ≥ 3 hepatic toxicity was observed in 1 patient. CONCLUSIONS: Two-week schedule of hypofractionated radiotherapy for small HCC was feasible with good local control and safety. This fractionation schedule can be used as an alternative treatment option for HCC located close to a critical normal organ if short-course SBRT is not feasible.
  Journal of Gastroenterology and Hepatology 04/2013;
• Article: Clinicopathological significance of S100 protein expression in cholangiocarcinoma.

  Yasunori Sato, Kenichi Harada, Motoko Sasaki, Yasuni Nakanuma
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  ABSTRACT: BACKGROUND AND AIM: Cholangiocarcinoma arising in the large bile ducts undergoes a multistep carcinogenesis process in chronic biliary diseases, and biliary intraepithelial neoplasia is known as a precursor lesion. This study examined the expression of S100 proteins in the multistep cholangiocarcinogenesis to clarify their clinicopathological significance. METHODS: Immunohistochemical analysis was performed for the expression of S100A2, S100A4, S100A6, and S100P. Bile concentrations of S100P were measured using enzyme-linked immunosorbent assay. RESULTS: The immunohistochemical expression of the S100 proteins was increased in biliary intraepithelial neoplasia as well as invasive adenocarcinoma of perihilar cholangiocarcinoma. Among the proteins, S100P expression was most drastically increased during the multistep carcinogenesis process. In cases with perihilar and extrahepatic cholangiocarcinoma, the immunohistochemical expression of S100A2 in cholangiocarcinoma cells significantly correlated with the histological grade, lymph node metastasis, clinical stage, and a poor survival rate of the patients. The bile levels of S100P were increased significantly in patients with cholangiocarcinoma compared to those in patients with lithiasis. Receiver operating characteristic curve analysis showed that S100P bile concentration was an indicator of cholangiocarcinoma with a sensitivity of 93% and a specificity of 70%. CONCLUSIONS: These results suggest that S100P may be useful for the detection of cholangiocarcinoma as tissue and bile biomarkers, and the immunohistochemical expression of S100A2 is a potential prognostic marker in cholangiocarcinoma patients.
  Journal of Gastroenterology and Hepatology 04/2013;