Seok-Ho Dong

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.

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.

Percutaneous Transhepatic Embolization of a Bronchobiliary Fistula Developing Secondary to a Biloma After Conventional Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma

Dear Sirs, A 53-year-old male underwent conventional transarterial chemoembolization (TACE) (using a combination of doxorubicin, lipiodol, and gelfoam) twice for treatment of multiple hepatocellular carcinoma (HCC) at our institution. Several tumors were located in the right lobe of the liver. His past medical history was significant and included lung and gastric cancer. He had undergone left lower lung lobectomy to treat a non-small cell lung cancer 4 years prior and subtotal gastrectomy with gastro-jejunostomy (the Billroth II operation) to treat advanced gastric cancer 3 years prior. One month after the second TACE, the patient presented with general weakness and abdominal pain with fever. An abdominal computed tomography (CT) scan revealed multiple intrahepatic duct (IHD) dilatations and bilomas in the right hepatic lobe (Fig. 1). Multiple percutaneous transhepatic drainages of the intrahepatic biloma and biliary duct drainage were performed to decompress the bilomas and the biliary tree. Over the next 2 months, the multiple bilomas became much smaller in size, and the clinical symptoms disappeared. Therefore, the drainage catheters were removed, and antibiotic treatment discontinued. However, 1 month after removal of the catheters, the patient developed a productive cough with sputum containing massive amounts of bile, accompanied by a persistent fever. Bronchoscopy revealed greenish biliptysis in the right bronchus (not shown). Follow-up CT revealed markedly decreased but residual IHD dilatation and bilomas, an ovoid fluid pool in the right subphrenic space, and right lower lung lobe consolidation (Fig. 2). Under ultrasonic guidance, a drainage catheter was inserted into the right intrahepatic biloma. Three days later, contrast medium injected through the drainage catheter opacified the right bile ducts and right lower-lobe segmental bronchi, extending into the right main bronchus and the trachea (Fig. 3). This confirmed the presence of a bronchobiliary fistula (BBF). Conservative management featuring continuous catheter drainage, balloon dilatation of the bile duct stricture, and

Predictors of Malignancy in “Pure” Branch-Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas without Enhancing Mural Nodules on CT Imaging: A Nationwide Multicenter Study

Background/Aims Presence of enhanced mural nodules, which can be visualized using computed tomography (CT), is one of high-risk stigmata in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). Conversely, the absence of enhanced mural nodules on preoperative imaging does not exclude malignant risk. The present study aimed to investigate other morphological features as predictors of malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT. Methods This retrospective study included 180 patients with surgically confirmed “pure” BD-IPMNs of the pancreas and no enhanced mural nodules on preoperative CT. The study was conducted at 15 tertiary referral centers throughout South Korea. Univariate and multivariate analyses were used to identify significant predictors of malignancy. Results BD-IPMNs with low-grade (n=84) or moderate-grade (n=76) dysplasia were classified as benign; those with high-grade dysplasia (n=8) or invasive carcinoma (n=12) were classified as malignant. The multivariate analysis revealed that cyst size ≥30 mm (odds ratio, 8.6; p=0.001) and main pancreatic duct diameter ≥5 mm (odds ratio, 4.1; p=0.01) were independent risk factors for malignancy in “pure” BD-IPMNs without enhanced mural nodules on CT. Endoscopic ultrasound detected enhanced mural nodules (6/82) that had been missed on CT, and two IPMNs with enhanced mural nodules were malignant. Conclusions In patients with “pure” BD-IPMNs who have no enhanced mural nodules on CT, cyst size ≥30 mm and main pancreatic duct diameter ≥5 mm may be associated with malignancy.