Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).

OBJECTIVE: To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. METHODS: A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). RESULTS: There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. CONCLUSIONS: We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

Outcomes of a multi-ethnic Asian population on combined treatment with clopidogrel and omeprazole in 12,440 patients.

Omeprazole is commonly co-prescribed with clopidogrel. Clopidogrel requires bio-activation by cytochrome P450 CYP2C19. Omeprazole may reduce clopidogrel's antithrombotic efficacy by inhibiting CYP2C19. Studies in Caucasians receiving omeprazole with clopidogrel showed no significant increase in death and myocardial infarction with this drug-drug interaction. There are limited large-scale studies in Asians, who may have a greater prevalence of CYP2C19 loss-of-function polymorphisms. A single centre retrospective cohort study was undertaken based on a review of medication records and prescription data. Patients prescribed clopidogrel from 2009 to 2012 were followed-up with until December 2012 (median:29 months). The primary outcome was all-cause mortality and secondary outcomes were myocardial infarction (MI), cerebrovascular accidents, and subsequent coronary interventions. Of 12,440 patients prescribed clopidogrel, 62%(n = 7714) were on omeprazole (63.8% Chinese, 13.9% Malay, 12.4% Indian, 10.0% others), and 38%(n = 4726) were not on omeprazole or other proton pump inhibitors (62.6% Chinese, 13.5% Malay, 10.7% Indian, 13.2% others). Mortality after co-prescription occurred in 14.3%(n = 1101) of patients, compared to 6.3%(n = 300) of patients prescribed clopidogrel only. Multivariate analysis using propensity score adjusted analysis showed no significant increase in all-cause mortality with co-prescription (adjusted hazards ratio [AHR] 1.13, [95%CI 0.95-1.35]). Patients on co-prescription had a higher risk of subsequent MI (16% vs 3.8%; AHR 2.03 [95%CI 1.70-2.44]), but not of cerebrovascular accidents (5.0% vs 2.0%; AHR 0.98 [95%CI 0.76-1.27]) or coronary interventions (1.7% vs 0.7%; AHR 1.28 [95%CI 0.83-1.96]). The risk of a subsequent MI was higher in the Malay (AHR 2.43 [95%CI 1.68-3.52]) and Chinese (AHR 2.06 [95%CI 1.63-2.60]) population as compared to the Indian (AHR 1.56 [95%CI 1.06-2.31]) population. In conclusion, the use of clopidogrel with omeprazole is associated with an increased risk of MI, but not mortality or stroke, in this multi-ethnic Asian population. These risks appear to vary among different ethnic groups.

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.

Advanced endoscopic imaging in gastric neoplasia and preneoplasia.

Conventional white light endoscopy remains the current standard in routine clinical practice for early detection of gastric cancer. However, it may not accurately diagnose preneoplastic gastric lesions. The technological advancements in the field of endoscopic imaging for gastric lesions are fast growing. This article reviews currently available advanced endoscopic imaging modalities, in particular chromoendoscopy, narrow band imaging and confocal laser endomicroscopy, and their corresponding evidence shown to improve diagnosis of preneoplastic gastric lesions. Raman spectrometry and polarimetry are also introduced as promising emerging technologies.

Investigation on the potential of Mueller matrix imaging for digital staining.

Digital staining based on Mueller matrix measurements and their derivatives was investigated. Mueller matrix imaging was performed at the microscopic level on gastric tissue sections. Full Mueller matrices (4 × 4) were reconstructed using recorded images, followed by the extraction of polarization parameters. The most effective parameters and their combinations were extracted from Mueller matrix elements, principal component scores and polarization parameters respectively to classify samples into three categories - i.e. cancer, dysplasia and intestinal metaplasia/normal glands for various regions of interest sizes. It was observed that two-step classification yielded higher classification accuracy than the traditional one-step classification and that pixel classification based on Mueller matrix elements yielded higher accuracy than that based on polarization parameters and derived principal components. Moreover, Mueller matrix images with a lower spatial resolution generated higher classification accuracy but those with a higher spatial resolution revealed more morphological details.ns. The original stained image (top) and the digital staining image (bottom).

Narrow-band imaging and white-light endoscopy with optical magnification in the diagnosis of dysplasia in Barrett's esophagus: results of the Asia-Pacific Barrett's Consortium.

OBJECTIVE: The advent and utility of new endoscopic imaging modalities for predicting the histology of Barrett's esophagus (BE) in real time with high accuracy appear promising and could potentially obviate the need to perform random biopsies where guidelines are poorly adhered to. We embarked on evaluating the performance characteristics of white-light endoscopy with magnification (WLE-z), narrow-band imaging with magnification (NBI-z) and a combination of both modalities. DESIGN: This was a prospective online study with 28 endoscopists from 11 countries (Asia-Pacific region) participating as assessors. In total, 35 patients with BE were assessed using 150 slides from WLE-z and NBI-z randomly arranged using a simple classification with corresponding histology. The overall Accuracy (Acc), Sensitivity (Sn), Specificity (Sp), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of WLE-z, NBI-z and a combination of both were calculated. RESULTS: The overall Acc for WLE-z and NBI-z images was 87.1 % and 88.7 %, respectively. When images from the two modalities were placed side by side, the Acc increased to 90.3 %. The Sn, Sp, PPV, and NPV of WLE-z were 48 %, 92 %, 45 %, and 93 % while with NBI-z, these improved to 89 %, 89 %, 56 %, and 98 %, respectively. When both imaging modalities were viewed together, they improved further to 93 %, 90 %, 61 %, and 99 %. CONCLUSION: The high NPV (99 %) when both WLE-z and NBI-z were used simultaneously indicates that areas with regular appearance that are diagnosed with confidence can effectively be left alone and not biopsied when performed at a skilled resourced center. This approach could potentially lead to a paradigm shift of how patients with BE are assessed.

Structured endoscopic ultrasonography (EUS) training program improved knowledge and skills of trainees: Results from the Asian EUS Group.

BACKGROUND AND AIM: A major reason impeding the growth of endoscopic ultrasound (EUS) in Asia is the lack of training availability. We aimed to prospectively evaluate the effectiveness of a short-term structured EUS training program in improving the knowledge and skill of EUS among trainees. METHODS: The study was conducted in six workshops in six countries including Sri Lanka, Pakistan, Thailand, Vietnam, Singapore and Philippines, within a year. Trainees were evaluated using written and skill tests before and after completion of the training. RESULTS: Pre- and post-workshop written tests from a total of 62 trainees were analyzed. Compared with pre-training, the trainees improved significantly in the overall mean (± SD) scores after the training (66.0 ± 0.3% to 77.5 ± 0.2%, P < 0.0001). Thirty-one trainees were randomly selected to undergo a skill test before and after the course. Compared with pre-training, the proportions of trainees who succeeded in locating each structure post-training were: celiac axis (36-80.5%), pancreatic body (51.5-80.5%), pancreatic body and tail (42-77.5%), splenic vein and artery (48.5-84%), left kidney (60-83%), and spleen (47-83%). Overall, there was a significant improvement in the proportion of trainees' successful localization of structures post-training compared to before training (P < 0.0001). CONCLUSION: Following a structured training program, trainees' knowledge and skills in EUS improved significantly. Structured training courses appear to be an effective way of imparting EUS knowledge and skills to aspiring endosonographers in the Asian region.

Roles of linear and circular polarization properties and effect of wavelength choice on differentiation between ex vivo normal and cancerous gastric samples.

Multispectral Mueller matrix imaging was performed over a spectral range from 470 to 632 nm on 4-µm unstained gastric tissue sections. A complete set of polarization parameters was derived. The combination of linear depolarization and linear retardance yields the highest accuracy in sample classification. When the depolarization of linearly polarized light due to scattering is independent of the orientation angle of the incident linear polarization vector, the derivation of linear polarization properties will require only 3×3 Mueller matrix, which would significantly reduce the complexity of the polarimetry imaging system. When additional parameters are needed to complement the two linear polarization parameters, retardance, circular depolarization, and depolarization can be included in classification in the order of preference. However, these additional parameters would require the measurement of 4×4 Mueller matrix. In addition, it appears that wavelength is not a critical factor in terms of classification accuracy for thin tissue sections in this study.

Diagnosis and treatment of Helicobacter pylori for peptic ulcer bleeding in clinical practice - factors associated with non-diagnosis and non-treatment, and diagnostic yield in various settings.

BACKGROUND/AIMS: To study the practice of clinicians in the diagnosis and treatment of H. pylori for peptic ulcer bleeding, and the diagnostic yield of H. pylori tests in various situations. MATERIALS AND METHODS: All consecutive patients aged ≥18 years who underwent esophagogastroduodenoscopy for the indications of coffee-grounds vomitus, hematemesis or melena with endoscopically diagnosed peptic ulcers were included. RESULTS: 374 patients were included. H. pylori testing was performed during acute bleeding for 296 patients. 80% of patients who tested negative for H. pylori during the acute episode were planned for repeat H. pylori testing. 11/88 patients who tested negative for H. pylori during the acute episode were positive for H. pylori during repeat testing (diagnostic yield 12.5%). Prior proton-pump inhibitor and antibiotic ingestion within 4 weeks of presentation was associated with lower diagnostic yield for H. pylori. On multivariate analysis, patient's age, systolic blood pressure, heart rate, activated partial thromboplastin time, and need for endoscopic treatment were associated with failure to take biopsies for H. pylori testing during acute episode. 100/106 patients tested positive for H. pylori during the acute episode of gastrointestinal bleeding had H. pylori treatment. CONCLUSION: Repeat H. pylori testing after index negative H. pylori testing during acute episodes gave a diagnostic yield of 12.5%, reinforcing the importance of repeat testing.

Comparison of probe-based confocal endomicroscopy with virtual chromoendoscopy and white-light endoscopy for diagnosis of gastric intestinal metaplasia.

OBJECTIVE: We prospectively compared the diagnostic performance of autofluorescence imaging (AFI), magnifying narrow band imaging (mNBI), and probe-based confocal laser endomicroscopy (pCLE) with white light endoscopy (WLE) for the diagnosis of gastric intestinal metaplasia (GIM), using histology as the "gold standard." DESIGN: Chinese >50 years old with history of GIM were prospectively recruited. All subjects underwent WLE, followed by AFI and NBI, and finally pCLE. Patients were randomized to undergo either AFI before NBI or vice versa. In each patient, a minimum of six sites (antrum lesser and greater curve, body lesser and greater curve, incisura, cardia, and any lesion) were each examined by WLE, AFI, NBI, and pCLE. The diagnoses were made real-time. Biopsies for histology were taken from all examined sites. pCLE videos also were reviewed off-site. Analysis was performed per-site. RESULTS: A total of 125 sites in 20 patients were examined. For diagnosing GIM, real-time pCLE had better sensitivity (90.9 vs. 37.9%, p < 0.001) and accuracy (88.0 vs. 64.8%, p < 0.001) compared with WLE. Sensitivity (90.9 vs. 68.2%, p = 0.001), specificity (84.7 vs. 69.5%, p = 0.042), and accuracy (88 vs. 68.8%, p < 0.001) of real-time pCLE were better than AFI. Sensitivity, specificity, and accuracy of real-time pCLE and mNBI for diagnosing GIM were similar. Off-site pCLE had significantly better accuracy for diagnosing GIM compared to WLE, AFI, and mNBI. Off-site pCLE had superior specificity (94.9 vs. 84.7%, p = 0.031) and accuracy (95.2 vs. 88.0%, p = 0.012) compared with real-time pCLE. CONCLUSIONS: pCLE was superior to AFI and WLE for diagnosing GIM. Off-site review improved performance of pCLE.

Factors determining diagnostic yield of endoscopic ultrasound guided fine-needle aspiration for pancreatic cystic lesions: a multicentre Asian study.

BACKGROUND AND AIM: The 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. METHODS: All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study. RESULTS: Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) 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 47 %. 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 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from the diagnostic yield of 50 % with more than one pass, p = 0.081. CONCLUSION: The cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study.

BACKGROUND: There is no satisfactory treatment for nonalcoholic steatohepatitis (NASH). The Bioenterics intragastric balloon (BIB) can be an effective treatment for weight reduction in obese patients. OBJECTIVE: We evaluated the efficacy of the BIB in improving the histology of NASH in obese patients. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: Obese patients with body mass indexes (BMI) ≥27 kg/m(2) and who had histologic evidence of NASH were recruited. INTERVENTION: Patients were randomly assigned to a step 1 American Heart Association (AHA) diet plus exercise and BIB placement or step 1 AHA diet plus exercise and sham BIB placement for a period of 6 months. MAIN OUTCOME MEASUREMENTS: Liver histology was the primary outcome measure recorded before and after treatment. RESULTS: A total of 18 patients completed the study. Baseline characteristics of the BIB and sham groups were similar. At 6 months, a significant reduction in the mean BMI was seen in the BIB group (1.52 vs 0.8; P = .0008). The median nonalcoholic fatty liver disease activity scores at the end of treatment were significantly lower in the BIB-treated compared with the sham-treated groups (2 [0.75] vs 4 [2.25]; P = .03). There was a trend toward improvement in the median steatosis scores (1 [0.75] vs 1 [1]; P = .075). There was no change in the median loblular inflammation, hepatocellular ballooning, or fibrosis scores in both groups after treatment. LIMITATIONS: Pilot study with small numbers and short duration. CONCLUSION: Results from this pilot study demonstrated that addition of BIB for 6 months provided a greater loss of BMI and improvement in 2 of 5 histologic parameters of nonalcoholic fatty liver disease. A longer study with larger numbers will be required to prove whether or not the therapy is meaningful in the treatment of NASH.

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Curry induces acid reflux and symptoms in gastroesophageal reflux disease.

BACKGROUND: There are limited data on the effect of curry on gastroesophageal reflux disease (GERD). Our objective was to study the effects of curry on GERD. METHODS: Symptomatic non-erosive gastroesophageal reflux disease (NERD) patients and healthy volunteers underwent ambulatory 24-h esophageal pH monitoring before consumption of either 400 or 800 ml of curry; they were monitored for 3 h thereafter for changes in esophageal pH and upper abdominal symptoms. Selected volunteers were monitored similarly after water ingestion. RESULTS: In total, 25 NERD patients (23 males; mean age, 45 years) and 19 volunteers (13 males; mean age, 22 years) participated. In both patients and volunteers, curry ingestion induced more esophageal acid exposure than did ingestion of a similar volume of water. Curry induced significantly more esophageal acid exposure in NERD patients than in volunteers. Upper abdominal symptoms and esophageal acid exposure were more severe and persisted longer in patients than in volunteers. CONCLUSION: Curry induced more acid reflux and caused worse symptoms in patients with NERD than in healthy individuals. Patients with NERD should be advised to avoid curry ingestion.

Risk factors for mortality in cirrhotic patients with sepsis.

BACKGROUND: Patients with cirrhosis and sepsis had increased mortality. AIM: Determine factors associated with increased in-hospital mortality in cirrhotic patients admitted for sepsis. METHODS: All cirrhotic patients admitted from 2004 to 2007 for sepsis were identified from hospital electronic database. Patients were included if they had liver cirrhosis and sepsis, defined as identified sources of infection, and at least one of fever, altered total white cell count, or raised C-reactive protein. Baseline characteristics, investigations, infections, and outcomes were collected. Main outcome measure was in-hospital mortality. RESULTS: A total of 205 admissions in 153 patients were included. In-hospital mortality rate was 24.4%. In predicting in-hospital death, area under the receiver-operating-characteristic curve for Child-Pugh score was 0.934, with optimum cut-off at 10 and above, while for model for end-stage liver disease (MELD) score was 0.751, with optimum cut-off at 17 and above. Four factors were significantly associated with in-hospital mortality on multivariate analysis: presence of >1 site of infection, pneumonia, Child's C status, and MELD score 17 and above. In-hospital mortality rate increased with more factors: 0% with no factor, 7% with one factor, 21% with two factors, 87% with three factors, and 100% with four factors. The mortality of those with <3 risk factors was significantly lower than those with three or more risk factors (7 vs. 91%, p = 0.000). CONCLUSIONS: Septic cirrhotic patients with pneumonia, >1 site of infection, Child's C cirrhosis, and high MELD score had a high mortality risk.

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

BACKGROUND: Confocal 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. OBJECTIVE: To 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. DESIGN: Blinded review of CLE images for the diagnosis of gastric cancer or intestinal metaplasia. SETTING: Tertiary care hospital. PATIENTS: CLE 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. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, and intragroup interobserver agreement of CLE image interpretation. RESULTS: Interpretation 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. LIMITATIONS: Single-center study. CONCLUSIONS: Experience in CLE was associated with greater accuracy in the diagnosis of intestinal metaplasia.

Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance.

AIM: To investigate the accuracy of serum alanine aminotransferase (ALT) in diagnosing lamivudine resistance and factors that contributed to abnormal serum ALT. METHODS: This was a retrospective study of chronic hepatitis B patients on lamivudine therapy who were followed for 3-mo with liver function tests and hepatitis B virus (HBV) DNA measurement. Lamivudine resistance was defined as HBV DNA ≥ 1 log from nadir on at least 2 occasions, confirmed by genotyping. Serum ALT levels in patients with lamivudine resistance were compared to serum ALT levels in those without lamivudine resistance. RESULTS: There were 111 patients with and 117 without lamivudine resistance. The area under the receiver operating characteristic of serum ALT to diagnose lamivudine resistance was 0.645 ± 0.037. Serum ALT > 42.5 U/L gave the best diagnostic accuracy with sensitivity = 61%, specificity = 60%, positive predictive value = 60%, negative predictive value = 61%, positive likelihood ratio = 1.53 and negative likelihood ratio = 0.65 for predicting lamivudine resistance, missing 39% of resistant patients. Using other serum ALT cutoffs, diagnostic accuracy was lower. By multivariate analysis, baseline abnormal serum ALT was associated with abnormal ALT during resistance (OR = 5.98, P = 0.003), and males were associated with serum ALT flares during resistance (OR = 8.9, P = 0.016). CONCLUSION: Serum ALT is inadequate for diagnosing lamivudine resistance and has implications where viral resistance testing is suboptimal and for reimbursement of rescue therapy.

Percutaneous paraumbilical embolization as an unconventional and successful treatment for bleeding jejunal varices.

A 48-year-old Indian male with alcoholic liver cirrhosis was admitted after being found unresponsive. He was hypotensive and had hematochezia. Esophagogastroduodenoscopy (EGD) showed small esophageal varices and a clean-based duodenal ulcer. He continued to have hematochezia and anemia despite blood transfusions. Colonoscopy was normal. Repeat EGD did not reveal any source of recent bleed. Twelve days after admission, his hematochezia ceased. He refused further investigation and was discharged two days later. He presented one week after discharge with hematochezia. EGD showed non-bleeding Grade 1 esophageal varices and a clean-based duodenal ulcer. Colonoscopy was normal. Abdominal computed tomography (CT) showed liver cirrhosis with mild ascites, paraumbilical varices, and splenomegaly. He had multiple episodes of hematochezia, requiring repeated blood transfusions. Capsule endoscopy identified the bleeding site in the jejunum. Concurrently, CT angiography showed paraumbilical varices inseparable from a loop of small bowel, which had herniated through an umbilical hernia. The lumen of this loop of small bowel opacified in the delayed phase, which suggested variceal bleeding into the small bowel. Portal vein thrombosis was present. As he had severe coagulopathy and extensive paraumbilical varices, surgery was of high risk. He was not suitable for transjugular intrahepatic porto-systemic shunt as he had portal vein thrombosis. Percutaneous paraumbilical embolization via caput medusa was performed on day 9 of hospitalization. Following the embolization, the hematochezia stopped. However, he defaulted subsequent follow-up.