Christopher Jen Lock Khor

Drug-induced liver injury at an Asian center: a prospective study.

Background/Aims: The aetiology of drug‐induced liver injuries (DILI) in Asia is different from that in the West, as anecdotal studies have shown that traditional complementary and alternative medicines (CAM) accounted for a major proportion of offending drugs in DILI in Asia. We aimed to study DILI in Asia prospectively, and to test whether DILI caused by traditional CAM was related to adulterants.

Asia-Pacific consensus recommendations for endoscopic and interventional management of hilar cholangiocarcinoma.

Hilar cholangiocarcinoma (HCCA) is one of the most common types of hepatobiliary cancers reported in the world including Asia–Pacific region. Early HCCA may be completely asymptomatic. When significant hilar obstruction develops, the patient presents with jaundice, pale stools, dark urine, pruritus, abdominal pain, and sometimes fever. Because no single test can establish the definite diagnosis then, a combination of many investigations such as tumor markers, tissue acquisition, computed tomography scan, magnetic resonance imaging/magnetic resonance cholangiopancreatography, endoscopic ultrasonography/intraductal ultrasonography, and advanced cholangioscopy is required. Surgery is the only curative treatment. Unfortunately, the majority of HCCA has a poor prognosis due to their advanced stage on presentation. Although there is no survival advantage, inoperable HCCA managed by palliative drainage may benefit from symptomatic improvement. Currently, there are three techniques of biliary drainage which include endoscopic, percutaneous, and surgical approaches. For nonsurgical approaches, stent is the most preferred device and there are two types of stents i.e. plastic and metal. Type of stent and number of stent for HCCA biliary drainage are subjected to debate because the decision is made under many grounds i.e. volume of liver drainage, life expectancy, expertise of the facility, etc. Recently, radio‐frequency ablation and photodynamic therapy are promising techniques that may extend drainage patency. Through a review in the literature and regional data, the Asia–Pacific Working Group for hepatobiliary cancers has developed statements to assist clinicians in diagnosing and managing of HCCA. After voting anonymously using modified Delphi method, all final statements were determined for the level of evidence quality and strength of recommendation.

Experienced versus inexperienced confocal endoscopists in the diagnosis of gastric adenocarcinoma and intestinal metaplasia on confocal images

BACKGROUNDnConfocal laser endomicroscopy (CLE) may be used to diagnose gastric cancer and intestinal metaplasia, but the impact of CLE experience on the accuracy of confocal diagnosis of gastric cancer and intestinal metaplasia is not clear.nnnOBJECTIVEnTo establish the sensitivity, specificity, and intragroup interobserver agreement of CLE image interpretation by 3 experienced (group 1) and 3 inexperienced (group 2) CLE endoscopists for diagnosing gastric intestinal metaplasia (GIM) and adenocarcinoma.nnnDESIGNnBlinded review of CLE images for the diagnosis of gastric cancer or intestinal metaplasia.nnnSETTINGnTertiary care hospital.nnnPATIENTSnCLE images obtained ex vivo from gastrectomy specimens with proven gastric cancer and CLE images obtained in vivo from Chinese subjects older than 50 years of age by using matched biopsy specimens as reference standards.nnnMAIN OUTCOME MEASUREMENTSnSensitivity, specificity, and intragroup interobserver agreement of CLE image interpretation.nnnRESULTSnInterpretation of in vivo images by group 1 was associated with higher sensitivity (95.2% vs 61.9%, P = .039) and higher specificity (93.3% vs 62.2%, P < .001) for GIM than interpretation by group 2. The agreement between interpretation by group 1 and histology for GIM was higher than that for group 2 (κ = 0.864 vs 0.217). The sensitivity (93.3% for group 1 vs 86.7% for group 2, P = 1.000) and specificity (87.7% for group 1 vs 80.7% for group 2, P = .344) of interpretation of ex vivo CLE images for the diagnosis of gastric adenocarcinoma was similar for groups 1 and 2.nnnLIMITATIONSnSingle-center study.nnnCONCLUSIONSnExperience in CLE was associated with greater accuracy in the diagnosis of intestinal metaplasia.

Evaluation of the Fukuoka Consensus Guidelines for intraductal papillary mucinous neoplasms of the pancreas: Results from a systematic review of 1,382 surgically resected patients

BACKGROUNDnInternational consensus guidelines to guide management of intraductal papillary mucinous neoplasms (IPMN) were revised in Fukuoka and published in 2012. However, despite widespread acceptance of the Fukuoka Consensus Guidelines (FCG), the utility of these guidelines have not been well-validated. This systematic review was performed to evaluate the clinical utility of the FCG.nnnDESIGNnA computerized search of the PubMed and Scopus databases was performed to identify all studies evaluating the utility of the FCG in surgically resected IPMN. IPMN were stratified according to the FCG as high risk (HR), worrisome risk (WR), and low risk (LR). HR and WR IPMN were termed FCG+ve and LR IPMN were termed FCG-ve.nnnRESULTSnSeven studies analyzing 1,382 patients were included. There were 402 malignant neoplasms (29%), including 242 invasive IPMNs. There were 1,000 IPMN classified as FCG+ve. The FCG+ve group had a positive predictive value (PPV) ranging from 27 to 62% and the FCG-ve group had negative predictive value ranging from 82 to 100%. Pooled analysis demonstrated that there was 362 of 1,000 (36%) malignant FCG+ve IPMN and 342 of 382 (90%) benign FCG-ve IPMN. PPV of the HR group and the WR groups alone were 104 of 158 (66%) and 75 of 261 (29%), respectively. Forty of 382 (11%), including 22 (6%) invasive FCG-ve IPMN, were malignant. Twenty-six malignant including 18 invasive FCG-ve IPMN were reported from a single study. When the results from this study were excluded, there were only 14 of 241 malignant neoplasms (6%), including 4 of 241 (2%) invasive FCG-ve IPMN in the remaining 6 studies.nnnCONCLUSIONnThe FCG+ve criteria had a similarly low PPV compared with the 2006 consensus criteria. Stratification of IPMN into HR and WR groups resulted in a higher PPV in the HR group. Some malignant and even invasive IPMN may be missed by the FCG criteria.

Factors Determining Diagnostic Yield of Endoscopic Ultrasound Guided Fine-Needle Aspiration for Pancreatic Cystic Lesions: A Multicentre Asian Study

Background and AimThe purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of surgical specimens were available.MethodsAll patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study.ResultsOf 298 patients with pancreatic cysts who underwent EUS, 132 (44.3xa0%) underwent FNA. In the entire cohort, pseudocysts and intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47xa0%. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44xa0% with one pass to 78xa0% with more than one pass (pxa0=xa00.016). In the absence of a solid component, the diagnostic yield was 29xa0% with one pass and was not significantly different from the diagnostic yield of 50xa0% with more than one pass, pxa0=xa00.081.ConclusionThe cytologic yield of EUS-FNA was 47xa0%. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%). Several IMs exhibited hypermethylation at DNA methylation valleys; however, IMs generally lack intragenic hypomethylation signatures of advanced malignancy. IM patients with shortened telomeres and chromosomal alterations were associated with subsequent dysplasia or GC; conversely patients exhibiting normal-like epigenomic patterns were associated with regression.

International consensus recommendations for difficult biliary access

ERCP is the standard procedure for endoscopic biliary therapy. The endoscopic approach to the ampulla followed by selective deep biliary cannulation is the first step before further therapy. Difficult biliary access can occur during endoscope intubation or when attempting selective biliary cannulation in normal or surgically altered anatomy. Difficult cannulation increases the risk of post-ERCP adverse events, particularly post-ERCP pancreatitis (PEP) and perforation. In normal anatomy, about 11% of therapeutic ERCPs may be considered difficult biliary cannulation. Biliary access in patients with surgically altered anatomy, such as Billroth II or Roux-en-Y anastomosis, is considered difficult because special instruments and maneuvers are often needed. Various methods are used to overcome difficult biliary access, including advanced ERCP-based techniques using precut papillotomy or double guidewires (DGWs), specialized instruments like echoendoscopes or device-assisted enteroscopy, or percutaneous approach. These techniques and procedures are more complex and carry significant risks, requiring specific training. This consensus aims to develop an evidence-based framework for biliary endoscopists to tackle difficult biliary access.

Per oral cholangiopancreatoscopy in pancreatico biliary diseases - Expert consensus statements

AIMnTo provide consensus statements on the use of per-oral cholangiopancreatoscopy (POCPS).nnnMETHODSnA workgroup of experts in endoscopic retrograde cholangiopancreatography (ERCP), endosonography, and POCPS generated consensus statements summarizing the utility of POCPS in pancreaticobiliary disease. Recommendation grades used validated evidence ratings of publications from an extensive literature review.nnnRESULTSnSix consensus statements were generated: (1) POCPS is now an important additional tool during ERCP; (2) in patients with indeterminate biliary strictures, POCS and POCS-guided targeted biopsy are useful for establishing a definitive diagnosis; (3) POCS and POCS-guided lithotripsy are recommended for treatment of difficult common bile duct stones when standard techniques fail; (4) in patients with main duct intraductal papillary mucinous neoplasms (IPMN) POPS may be used to assess extent of tumor to assist surgical resection; (5) in difficult pancreatic ductal stones, POPS-guided lithotripsy may be useful in fragmentation and extraction of stones; and (6) additional indications for POCPS include selective guidewire placement, unexplained hemobilia, assessing intraductal biliary ablation therapy, and extracting migrated stents.nnnCONCLUSIONnPOCPS is important in association with ERCP, particularly for diagnosis of indeterminate biliary strictures and for intra-ductal lithotripsy when other techniques failed, and may be useful for pre-operative assessment of extent of main duct IPMN, for extraction of difficult pancreatic stones, and for unusual indications involving selective guidewire placement, assessing unexplained hemobilia or intraductal biliary ablation therapy, and extracting migrated stents.

Asian consensus statements on endoscopic management of walled-off necrosis Part 1: Epidemiology, diagnosis, and treatment.

Walled‐off necrosis (WON) is a relatively new term for encapsulated necrotic tissue after severe acute pancreatitis. Various terminologies such as pseudocyst, necroma, pancreatic abscess, and infected necrosis were previously used in the literature, resulting in confusion. The current and past terminologies must be reconciled to meaningfully interpret past data. Recently, endoscopic necrosectomy was introduced as a treatment option and is now preferred over surgical necrosectomy when the expertise is available. However, high‐quality evidence is still lacking, and there is no standard management strategy for WON. The consensus meeting aimed to clarify the diagnostic criteria for WON and the role of endoscopic interventions in its management. In the Consensus Conference, 27 experts from eight Asian countries took an active role and examined key clinical aspects of WON diagnosis and endoscopic management. Statements were crafted based on literature review and expert opinion, employing the modified Delphi method. All statements were substantiated by the level of evidence and the strength of the recommendation. We created 27 consensus statements for WON diagnosis and management, including details of endoscopic procedures. When there was not enough solid evidence to support the statements, this was clearly acknowledged to facilitate future research. Proposed management strategies were formulated and are illustrated using flow charts. These recommendations, which are based on the best current scientific evidence and expert opinion, will be useful for guiding endoscopic management of WON. Part 1 of this statement focused on the epidemiology, diagnosis, and timing of intervention.

Metronidazole-resistant Helicobacter pylori in an urban Asian population.

Background : Helicobacter pylori eradication is the mainstay in the treatment of H. pylori‐associated peptic ulcer disease. Metronidazole is an important component in most eradication regimens. However, the presence of metronidazole‐resistant H. pylori adversely affects the efficacy of such regimens. We aimed to study the prevalence of metronidazole resistance in our population, and the factors associated with its presence.