Yong Dae Kwon

Gastrointestinal and biliary stents

Advances in stent design have led to a substantial increase in the use of stents for a variety of malignant and benign strictures in the gastrointestinal tract and biliary system. Whereas early stents were mostly composed of plastic, the majority of contemporary stents are self‐expanding metal stents that are composed of either nitinol or stainless steel. These stents are able to exert an adequate expansile force and, at the same time, are highly flexible and biocompatible. Covered stents have been introduced to minimize tumor ingrowth through the metal mesh but are associated with higher rates for spontaneous migration. This has led to the development of covered stents with uncovered ends and stents with both covered and uncovered layers. Drug‐eluting and biodegradable stents are also likely to become available in the near future. Although stents appear to be the preferred form of palliation for some patients with advanced cancer, many patients will benefit from a multidisciplinary approach that usually includes surgeons and oncologists.

Usefulness of Non-invasive Markers for Predicting Significant Fibrosis in Patients with Chronic Liver Disease

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as ≥F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, α2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, α2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

Stretching Causes Extensive Changes of Gastric Submucosa: Is It Acceptable to Define 500 microm as the Safe Margin?

BACKGROUND/AIMS Endoscopic mucosal resection can cure early gastric cancer. The risk of lymphatic metastasis is related to the depth of submucosal invasion by the mucosal malignancy, with a resection depth of 500 microm generally accepted as a safe cut-off. However, excessive thinning induced by stretching of the resected tissue sometimes preventing a precise diagnosis. We studied the effects of stretching on different layers and sites of gastric tissue. METHODS Porcine stomachs were cut into 2.0x2.0 cm pieces, and pieces from body were stretched to 2.5, 3.0, and 3.5 cm. Pieces from the cardia, body, and antrum were also stretched to 3.0 cm. The thickness of each layer was measured and analyzed statistically. RESULTS Whole gastric wall and submucosal layers showed gradual thinning, with stretching to 3.5 cm tearing the tissues and resulting in imperfect extension. The submucosa was thinner in body tissue than in cardia and antrum tissues. Stretching to 3.0 cm induced a consistent decrease in submucosal thickness (30-70%). The change in thickness varied widely between individual samples. CONCLUSIONS A resection margin of 500 microm might be insufficient for the complete removal of malignancy. Moreover, the thickness of the submucosal layer differs with the gastric site and between individuals. Future studies are needed to confirm the findings in human tissue.

Changes in liver stiffness during the course of acute hepatitis A.

BACKGROUNDS/AIMS In some patients with chronic hepatitis, liver stiffness (LS) findings do not reflect fibrosis stage. This study was performed to evaluate whether acute liver inflammation could influence LS findings. METHODS Patients with acute hepatitis A admitted to our hospital were included. Hepatitis was classified on admission using serum ALT and bilirubin levels as inflammation phase, jaundice phase, or recovery phase. Patients who admitted during the recovery phase (whose ALT and bilirubin levels fell continuously during hospitalization) and therefore, their peak-ALT and peak bilirubin levels could not be determined were exduded. Enrolled patients underwent FibroScan during hospitalization and after discharge. RESULTS Seventy-six patients with acute hepatitis A were enrolled (median age, 29 years; 46 men and 30 women). Among them, 33 (43.4%) and 43 (56.6%) patients were admitted during the inflammation phase and jaundice phase, respectively. For patients admitted during the inflammation phase, mean (+/-SD) time from symptom-onset day to maximum ALT level was 7 (+/-3) days. For all patients, mean time from symptom-onset to maximum bilirubin level was 11 (+/-4) days. Mean LS during admission was 8.9 (+/-Pa (median, 8.4 kPa). LS was significantly correlated with serum bilirubin level, which was the only factor found to be significantly associated with the increased LS (>7.08 kPa). In all patients, LS increased gradually from the symptom-onset and peaked at 8-9 days later. CONCLUSIONS Severe hepatic inflammation can affect the LS findings and thus, care is required when assessing fibrosis stage using LS measurement in patients with severe inflammation.

Gilbert's syndrome phenotypically expressed as Crigler-Najjar syndrome type II

TO THE EDITOR: Familial non-hemolytic unconjugated hyperbilirubinemia, including Crigler-Najjar syndrome (CN) type I, CN type II, and Gilbert’s syndrome (GS), is associated with a defect in isoenzyme 1A of UDP-glucuronosyltransferase (UGT1A), which is essential for the efficient biliary excretion of bilirubin. GS, the mildest form, clinically manifests a mild, unconjugated hyperbilirubinemia [1 3]. Although these levels may be higher in the presence of hemolysis, fasting, stress, or intermittent infection, they rarely increase to 5 mg/dL [4]. We experienced a patient with GS who was initially misdiagnosed with CN type II because his serum bilirubin levels transiently increased to 11 mg/dL. A healthy 21-year-old man was admitted to our hospital for the evaluation of jaundice. A month earlier, he had visited a local hospital with nausea, poor oral intake, and epigastric pain lasting for one week. In that hospital, his total serum bilirubin level was determined to be 11.26 mg/dL. After undergoing conservative management for two weeks, the level decreased to 5.5 mg/dL. The patient had had intermittent laboratory tests during a general medical check-up several years previously, and the results revealed only mild elevation of serum bilirubin (1 2 mg/dL). A physical examination was unrevealing and the results of initial laboratory tests were as follows: white blood count, 6700/mm; hemoglobin, 12.4 g/dL; platelets, 262,000/mm; total bilirubin, 5.47 mg/dL; direct bilirubin, 1.47 mg/dL; protein, 7.2 g/dL; albumin, 4.6 g/dL; alanine aminotransferase, 18 IU/L; aspartate aminotransferase, 15 IU/L; gamma-glutamyl transferase, 22 IU/L; alkaline phosphatase, 122 IU/L. Viral markers for hepatitis B and C were negative. The following laboratory tests were performed to rule out the possibility of combined hemolysis: plasma hemoglobin, 3.9 mg/dL; haptoglobin, 38.0 mg/dL; lactic dehydrogenase, 289 IU/L; direct/indirect Coombs’ tests, negative/negative; and peripheral blood smear, normocytic normochromic red blood cells with no evidence of hemolysis. The results of a liver biopsy and of an abdominal sonogram were normal. Upper gastrointestinal endoscopy showed a healing-stage ulcer on the duodenal bulb, with no evidence of recent bleeding. To evaluate the cause of hyperbilirubinemia, the patient was subjected to a fasting test. After a 48-h fast, his total serum bilirubin level increased from 4.94 mg/ dL before the test to 6.99 mg/dL after the test. Furthermore, we collected a blood sample from the patient and directly determined the DNA sequences of both strands of the promoter region and all exons of the gene for UGT1A by polymerase chain reaction (PCR). The patient was found to be heterozygous for the sequence variant (TA)6/(TA)7 in the promoter region of UGT1A1 (Figure 1A). Moreover, a singlebase substitution in one allele of the UGT1A1 promoter at nucleotide /3279 (T /G) was found (Figure 1B). The patient also had a G-to-A transition in exon 1 of UGT1A1 at nucleotide 211 on one allele (Figure 1C). The sequence of exons 1 5 on the other allele was normal. The patient was discharged with medication for a duodenal ulcer, and no symptoms developed. Three months after discharge, his total serum bilirubin level had decreased to 2.1 mg/dL.