Ken Liu

Iron deficiency anaemia: a review of diagnosis, investigation and management.

Iron deficiency anaemia (IDA) is the most common form of anaemia worldwide. In men and postmenopausal women the commonest cause of IDA is blood loss from lesions in the gastrointestinal tract, making it a common cause of referral to gastroenterologists. Causes of IDA relate either to blood loss or iron malabsorption. After confirmation with laboratory tests, gastrointestinal evaluation is almost always indicated to exclude gastrointestinal malignancy. Specific patient groups such as premenopausal women, patients with low-normal ferritin and iron-deficient patients without anaemia may need an individualized approach. A small proportion of patients have recurrent or persistent IDA despite negative standard endoscopies. These patients with obscure gastrointestinal bleeding usually require evaluation of the small bowel with capsule endoscopy or double balloon enteroscopy. Treatment should involve prompt iron replacement plus diagnostic steps directed towards correcting the underlying cause of IDA. Oral iron replacement is cheap and effective, but parenteral (intravenous) therapy may be required due to intolerance, noncompliance or treatment failure with oral therapy.

Review article: the diagnosis and investigation of obscure gastrointestinal bleeding

Aliment Pharmacol Ther 2011; 34: 416–423

Fully covered self-expandable metal stents for treatment of benign biliary strictures.

p t Endoscopic therapy has now superseded surgery as firstline therapy for benign biliary strictures (BBSs). The use of plastic stents (PSs), although effective in treating BBSs, has been limited by their short stent patency and the need for repeated endoscopic procedures to achieve stricture resolution. Recently, fully covered self-expandable metal stents (FCSEMSs) have been increasingly proposed as a new paradigm for treating BBSs. The effectiveness of FCSEMSs in achieving long-term stricture resolution has been reported in numerous studies. The versatility of FCSEMSs has also been demonstrated by their use in both transplantation and nontransplantation BBSs and as both firstand second-line therapy settings. Adverse events of FCSEMSs including pancreatitis, cholangitis, secondary strictures, and pain are usually infrequent and can be successfully managed conservatively. Stent migration can be problematic for FCSEMSs; however, antimigratory modifications such as anchor fins and flared ends have shown promise in preventing this. The use of FCSEMSs for the treatment of BBSs is feasible, effective, and safe. Clinical success rates are similar to those of PSs, with the advantage of fewer procedures. Endoscopic stenting of benign biliary strictures (BBSs) is now first-line therapy. It is preferred over surgical treatment because of its less invasive approach, low morbidity, and convenience.1,2 The causes of BBSs are diverse (Table 1), with the 2 most common causes being postsurgical strictures (eg, from cholecystectomy or orthotopic liver transplantations) and chronic pancreatitis. The use of plastic stents (PSs), in particular, the use of multiple simultaneous stents, has been shown to be effective in treating BBSs with success rates of 62% to 89%.3-5 PSs, however, are limited by their propensity to occlude because of bacterial biofilm deposition in the lumen. They

Colorectal cancer screening practise is influenced by ethnicity of medical practitioner and patient.

Background and Aim:  Colorectal cancer (CRC) screening improves survival and requires appropriate recommendation by general practitioners (GPs). Screening practises may be influenced by barriers related to ethnicity and training.

Prognostic Value of Controlled Attenuation Parameter by Transient Elastography

Objectives:Liver stiffness measurement (LSM) by transient elastography (TE) has been shown to predict outcomes in patients with liver disease. While controlled attenuation parameter (CAP) measurement can accurately quantify hepatic steatosis, its prognostic value is unknown. We aim to determine if CAP is predictive for liver-related events (LRE), non-hepatocellular carcinoma (HCC) cancers, and cardiovascular events (CVE).Methods:Consecutive patients with both a reliable LSM and ≥10 successful CAP measurements by TE from August 2012 to March 2016 were included in the analysis. LRE were defined as HCC or hepatic decompensation. CVE were defined as acute coronary syndrome (ACS), cerebrovascular accident (CVA), or coronary intervention (stenting or bypass).Results:Of the 5,848 patients that were examined, 4,282 (56.7% male, median age 57 years) had adequate follow-up, reliable LSM (median 6.1 kPa), and ≥10 CAP measurements (median 250 dB/m). Indications for TE were: suspected non-alcoholic fatty liver disease (NAFLD) (40.7%), hepatitis B (HBV) (37.0%), hepatitis C (2.9%), and others (19.4%). During 8,540 patient-years of follow-up, there were 45 patients with LRE (34 HCC, 33 decompensations), 73 with newly diagnosed non-HCC cancers, and 65 with CVE (27 ACS, 25 CVA, and 35 coronary interventions). CAP did not predict LRE, non-HCC cancer, or CVE on univariate analysis. On multivariate analysis, LSM, male sex, platelet count, serum albumin, and HBV etiology independently predicted LRE; age was the only independent predictor of non-HCC cancer; while age, fasting blood glucose, total cholesterol, and creatinine predicted for CVE. Subgroup analyses of viral hepatitis and NAFLD patients revealed similar results.Conclusion:Neither the presence nor the severity of hepatic steatosis as measured by CAP predict LRE, cancer, or CVE in the short term.

O-GlcNAc transferase promotes fatty liver-associated liver cancer through inducing palmitic acid and activating endoplasmic reticulum stress

BACKGROUND & AIMS O-GlcNAc transferase (OGT) is a unique glycosyltransferase involved in metabolic reprogramming. We investigated the functional role of OGT in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). METHODS The biological function of OGT in NAFLD-HCC was determined by gain- or loss- of OGT functional assays in vitro and in nude mice. OGT target factors and pathways were identified by liquid chromatography-tandem mass spectrometry (LC-MS), promoter luciferase assay, DNA binding activity assay and Western blot. RESULTS OGT was upregulated in 12 out of 18 (66.7%) NAFLD-HCC tumor tissues by transcriptome sequencing, which was confirmed in additional NAFLD-HCC tumor tissues and cell lines. Biofunctional investigation demonstrated that OGT significantly increased cell growth (p<0.001), clonogenicity (p<0.01), migration and invasion (p<0.05) ability in vitro, and promoted xenograft tumor growth as well as lung metastasis in nude mice. The oncogenic effect of OGT was investigated, we found that OGT significantly induced palmitic acid production identified by LC-MS, which enhanced the protein expression of endoplasmic reticulum (ER) stress masters of glucose-regulated protein 78 and inositol-requiring enzyme 1α. Consequently, OGT significantly activated JNK/c-jun/AP-1 cascade by increasing protein expression of p-JNK, p-c-Jun and activation of AP-1; and induced NF-κB pathway through enhancing the protein levels of p-IKKα/ p-IKKβ, p-p65, p-p50 and the NF-κB DNA binding activity. Notably, OGT inhibition by its antagonist (ST045849) suppressed cell proliferation in vitro (p<0.001) and in xenograft mice models (p<0.05). CONCLUSIONS OGT plays an oncogenic role in NAFLD-associated HCC through regulating palmitic acid and inducing ER stress, consequently activating oncogenic JNK/c-jun/AP-1 and NF-κB cascades. LAY SUMMARY OGT, a unique glycosyltransferase enzyme, was identified to be upregulated in non-alcoholic fatty liver disease-associated hepatocellular carcinoma tissues by transcriptome sequencing. Here, we found that OGT plays a role in cancer by promoting tumor growth and metastasis in both cell models and animal models. This effect is mediated by the induction of palmitic acid.

Predictors of success for double balloon assisted endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y anastomosis.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with roux‐en‐Y anastomosis (REYA) is challenging. Use of double balloon enteroscope‐assisted ERCP (DBE‐ERCP) has been successful. We aim to determine predictors of successful biliary cannulation with DBE‐ERCP in patients with REYA.

Targeting the vasculature in hepatocellular carcinoma treatment: Starving versus normalizing blood supply.

&NA; Traditional treatments for intermediate or advanced stage hepatocellular carcinoma (HCC) such as transarterial chemoembolization (TACE) and anti‐angiogenesis therapies were developed to starve tumor blood supply. A new approach of normalizing structurally and functionally abnormal tumor vasculature is emerging. While TACE improves survival in selected patients, the resulting tumor hypoxia stimulates proliferation, angiogenesis, treatment resistance and metastasis, which limits its overall efficacy. Vessel normalization decreases hypoxia and improves anti‐tumor immune infiltrate and drug delivery. Several pre‐clinical agents aimed at normalizing tumor vasculature in HCC appear promising. Although anti‐angiogenic agents with vessel normalizing potential have been trialed in advanced HCC with modest results, to date their primary intention had been to starve the tumor. Judicious use of anti‐angiogenic therapies is required to achieve vessel normalization yet avoid excessive pruning of vessels. This balance, termed the normalization window, is yet uncharacterized in HCC. However, the optimal class, dose and schedule of vascular normalization agents, alone or in combination with other therapies needs to be explored further.

Oral and upper gastrointestinal Crohn's disease

Crohns disease is a heterogeneous, inflammatory condition that can affect any location of the gastrointestinal tract. Proximal gastrointestinal involvement occurs in 0.5–16% of patients, and it is usually diagnosed after recognition of intestinal disease. Symptoms are often mild and nonspecific; however, upper gastrointestinal disease predicts a more severe Crohns phenotype with a greater frequency of complications such as obstruction and perforation. Gastroscopy and biopsy is the most sensitive diagnostic investigation. There is a paucity of data examining the treatment of this condition. Management principles are similar to those for intestinal disease, commencing with topical therapy where appropriate, progressing to systemic therapy such as glucocorticoids, 5‐aminosalicylic acid, immunomodulators, and biologics. Acid suppression therapy has symptomatic but no anti‐inflammatory benefit for gastroduodenal and esophageal involvement. Surgical intervention with bypass, strictureplasty, or less frequently, endoscopic balloon dilation may be required for complications or failed medical therapy.

Epidemiology and outcomes of primary sclerosing cholangitis with and without inflammatory bowel disease in an Australian cohort.

Epidemiological data on primary sclerosing cholangitis (PSC) outside the Northern hemisphere are limited. Similarly, the impact of inflammatory bowel disease (IBD) on PSC outcomes remains unclear. We aimed to study the epidemiology and outcomes of PSC patients with and without IBD in an Australian cohort.