Young-Woon Chang

Interleukin-1B (IL-1B) polymorphisms and gastric mucosal levels of IL-1β cytokine in Korean patients with gastric cancer

Interleukin‐1B and IL‐1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL‐1B‐511T polymorphism and the risk of GC in Asians. We tested for an association between IL‐1 loci polymorphisms with increased gastric mucosal levels of IL‐1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL‐1A‐889, IL‐1B‐31, IL‐1B‐511 and IL‐1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL‐1β cytokine was measured using an ELISA. The frequencies of IL‐1A, IL‐1B‐511, IL‐1B‐31 and IL‐1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal‐type GC showed a higher frequency of IL‐1B‐31T homozygotes (OR = 2.2; 95% CI = 1.1–4.3) compared with controls. Risk was also significantly increased in these patients for IL‐1B‐31T homozygotes compared with patients with diffuse‐type GC (OR = 3.4; 95% CI = 1.5–7.7). As in Caucasian populations, linkage disequilibrium between IL‐1B‐31 and IL‐1B‐511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL‐1B‐31T/IL‐1B‐511C) was opposite (IL‐1B‐511T/IL‐1B‐31C). Mucosal IL‐1β levels in H. pylori‐infected GC patients were higher in patients homozygous for IL‐1B‐31T compared with IL‐1B‐31C/T and IL‐1B‐31C/C. Thus, the combined effects of H. pylori infection and IL‐1B‐31T/IL‐1B‐511C polymorphisms with enhanced mucosal IL‐1β production contributed to the development of intestinal‐type GC in this Korean population.

The incidence and clinical characteristics of symptomatic propylthiouracil-induced hepatic injury in patients with hyperthyroidism: a single-center retrospective study

OBJECTIVES:Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course.METHODS:Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes.RESULTS:Four hundred ninety-seven patients (age 42.6 ± 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 ± 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 ± 288 μmol/L, 143 ± 111 U/L, and 265 ± 81 U/L; normal, <117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 ± 46.4) days after the PTU withdrawal.CONCLUSIONS:Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.

Role of Helicobacter pylori infection among offspring or siblings of gastric cancer patients

A positive family history is an increased risk factor for gastric cancer within family members, and one of the possible causes of this is the intrafamilial clustering of Helicobacter pylori infection. Our study examined the prevalence of H. pylori infection, serum antibodies to CagA and VacA and atrophic gastritis and/or intestinal metaplasia in the offspring or siblings of gastric cancer patients. A total of 726 subjects included 300 relatives of 300 separate gastric cancer patients and 426 controls. All subjects underwent upper gastrointestinal endoscopic examination with a rapid urease test. Blood samples were obtained to test for the presence of serum antibodies to the CagA and VacA proteins of H. pylori. The prevalence of H. pylori infection was higher in relatives of cancer patients (75.3%) than in controls (60.1%), and the adjusted odds ratio was 2.1 (95% CI 1.5–2.9). When either siblings or 2 or more family members were gastric cancer patients, the prevalence of H. pylori infection was much higher compared to the prevalence in controls. There was no specific relationship between CagA and VacA, and H. pylori infection. Atrophic gastritis and/or intestinal metaplasia were more frequently found in H. pylori‐infected relatives of cancer patients (26.1%) than in H. pylori‐infected controls (12.9%). These results strongly support a role for H. pylori infection in familial aggregation of gastric cancer. The prophylactic eradication of H. pylori infection in the offspring or siblings of gastric cancer patients may be clinically beneficial.

Dedifferentiation of conditionally immortalized hepatocytes with long-term in vitro passage.

The rat hepatocytes were immortalized using a temperature-sensitive mutant of SV40 large T antigen (tsT) to develop as a possible substitute for primary hepatocytes. Four rat hepatocyte lines that have been developed and maintained more than passage 50, were characterized for their cellular morphology, T antigen and p53 expression, chromosomes, liver-specific differentiation, telomerase activity and anchorage independent growth. All of four cell lines showed a typical epithelial cell morphology, but the population-doubling time became short with passage: 18 to 60%. T antigen expression was increased with passage about 3 to 65 times at permissive temperature but decreased significantly at non-permissive temperature. The expression level of p53 unchanged during passages was also decreased at non-permissive temperature. The distribution of chromosome number changed somewhat with passage. The production levels of albumin and urea in four cell lines were 2.4 to 13.0% and 7.5 to 19.9% of those produced in primary hepatocytes, respectively and were decreased to an undetectable level with passage. Telomerase activity was increased 10 fold following immortalization of cells, but anchorage independent growth of cells did not develop. These results indicate that conditionally immortalized hepatocytes become dedifferentiated with in vitro passage, which may be caused by marked chromosomal damages that occur with compulsive and continuous replications by the increment of T antigen content with passage and its sequential inhibition of p53 function.

Liver cirrhosis developed after ketoconazole‐induced acute hepatic injury

Abstract  We describe a previously healthy woman who developed liver cirrhosis as a sequela of acute hepatic injury that was induced by ketoconazole administration to treat onychomycosis. The initial presentation of the disease was of a typical acute hepatitis, characterized by nausea, anorexia, fatigue, and jaundice that developed during the administration of ketoconazole. Many other causes of hepatitis were absent in the patient. Even though the hepatic injury was gradually resolved for several months after cessation of the drug, the liver function was not completely restored. Six months after the onset of illness, a follow‐up abdominal computed tomography and peritoneoscopic liver biopsy were performed. They revealed a marked reduction in the liver volume and a definite cirrhotic change, which persisted for more than 5 years. The case suggests that the administration of ketoconazole can cause liver cirrhosis through acute hepatic injury within a short time under certain circumstances.

Survival of conditionally immortalized hepatocytes in the spleen of syngeneic rats.

Background: Hepatocyte transplantation has been shown to be effective in the treatment of liver failure; however, the shortage of donor organs limits its clinical application. Several reports have suggested that conditionally immortalized hepatocytes (CIH) could be an alternative to primary hepatocytes. However, CIH are known to undergo apoptosis in vitro at a non‐permissive temperature, which is similar to body temperature.

A Case of Santorinicele without Pancreas Divisum: Diagnosis with Multi-detector Row Computed Tomography

A santorinicele is defined as a focal cystic dilatation of the terminal portion of the dorsal pancreatic duct at the minor papilla. Most cases reported previously were associated with pancreas divisum and a santorinicele without pancreas divisum is known to be rare. We recently experienced a typical case of a santorinicele without pancreas divisum in a 67-yr-old woman with abdominal pain and hematochezia, subsequently proven to be the result of an ischemic colitis. The santorinicele was diagnosed incidentally with multi-detector row computed tomography using a minimum intensity projection technique, which clearly showed a cystic dilatation of the terminal portion of the dorsal pancreatic duct and a communication between the ventral and dorsal pancreatic ducts. This finding was also confirmed by a magnetic resonance cholangiopancreatography.

Autoimmune cholangitis in a patient with thymoma.

Abstract  Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non‐suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35‐year‐old woman with autoimmune cholangitis associated with thymoma who presented with pruritis, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma‐glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non‐suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English‐written literature.

Oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor: A case report

Gastric adenocarcinoma is one of the most common malignancies worldwide. Histochemical and immunohistologic analyses classify the phenotypes of gastric adenocarcinoma into several groups based on the variable clinical and pathologic features. A new and rare variant of gastric adenocarcinoma with chief cell differentiation (GA-CCD) has recently been recognized. Studies reporting the distinct clinicopathologic characteristics proposed the term oxyntic gland polyp/adenoma because of the benign nature of the GA-CCD. Typically, GA-CCD is a solitary mucosal lesion that develops either in the gastric cardia or fundus. Histologically, this lesion is characterized by tightly clustered glands and anastomosing cords of chief cells. Immunohistochemically, GA-CCD is diffusely positive for mucin (MUC) 6 and negative for MUC2 and MUC5AC. However, other gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have been difficult to exclude. Because GA-CCD tends to be endoscopically misdiagnosed as a neuroendocrine tumor or fundic gland polyp, comprehensive assessment and observation by an endoscopist are strongly recommended. Herein, we report a rare case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor that was successfully removed by endoscopic mucosal resection.

Congenital Jejunal Diverticular Bleeding in a Young Adult

Diverticular bleeding of the small bowel is rare and occurs primarily in adults aged more than 60 years. In younger adults, Meckel’s diverticulum, a true diverticulum that congenitally occurs in the distal ileum, is the most common cause of diverticular bleeding of the small bowel. Unlike Meckel’s diverticula, other kinds of small bowel diverticula are not congenital and their incidence is related to age. Furthermore, congenital true diverticular bleeding of the jejunum in adults is very rare. We report the case of a 24-year-old man with subepithelial tumor-like lesion accompanied with obscure overt gastrointestinal bleeding. This lesion was initially suspected to be a subepithelial tumor based on radiologic tests and capsule endoscopy. He was finally diagnosed with a congenital true diverticulum in the jejunum with the appearance of a Meckel’s diverticulum after surgical resection.