• Journal of Gastric Cancer
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• v.22 no.4
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• pp.339-347
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• 2022

Purpose: Lymphovascular invasion is a criterion for non-curative resection in patients who have undergone endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to determine the rate of extragastric metastasis (EGM) and identify the predictors of EGM in patients with negative resection margins (R0 resection) and lymphovascular invasion in post-ESD pathology. Materials and Methods: A total of 2,983 patients underwent ESD for EGC. Among them, 110 had a pathology of R0 resection and positive lymphovascular invasion. Patients underwent additional gastrectomy (n=63) or further follow-up without gastrectomy (n=47). Results: The 110 patients were assigned to one of the 3 groups according to ESD indications based on post-ESD pathology. The first group satisfied the absolute indication for ESD (n=18), the second group satisfied the expanded indications for ESD (n=34), and the last group satisfied the beyond indication (n=58). The number of occurrences of EGM in each group was 1 (5.6%), 3 (8.8%), and 3 (5.2%), respectively. The logistic regression analysis adjusted for age, sex, tumor size, and indication for ESD, showed that larger tumor size was associated with EGM (odds ratio, 1.76; 95% confidence interval, 1.00-3.10; P=0.048). In contrast, ESD indication criteria did not affect EGM (P=0.349). Conclusions: Tumor size was the only predictive indicator for EGM in patients who underwent R0 resection and lymphovascular invasion on post-ESD pathology. Even patients with pathology corresponding to the absolute indication criteria of ESD had lymphovascular invasion, which means that they require additional gastrectomy due to the risk of EGM.

• IMMUNE NETWORK
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• v.21 no.5
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• pp.37.1-37.17
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• 2021

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

• Journal of Preventive Medicine and Public Health
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• v.40 no.1
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• pp.23-28
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• 2007

Objectives : Chronic infections with hepatitis B or C and alcoholic cirrhosis are three well-known major risk factors for liver cancer. Diabetes has also been suggested as a potential risk factor. However, the findings of previous studies have been controversial in terms of the causal association. Therefore, the aim of this study was to evaluate the association between serum glucose levels and liver cancer development in a Korean cohort. Methods : Thirty-six liver cancer cases were identified in the Korean Multi-Center Cancer Cohort (KMCC). Baseline information on lifestyle characteristics was obtained via questionnaire. Serum glucose levels were measured at the study's enrollment. Relative risks (RRs) were estimated using a Cox proportional hazard regression model. The adjusting variables included age, gender, smoking history, alcohol consumption, body mass index, and hepatitis B surface antigen (HBsAg) seropositivity. Results : The RRs of serum glucose for liver caner were 1.20 (95% CI = 0.48-2.99) for the category of 100 to 125 mg/dL of serum glucose and 2.77 (95% CI = 1.24-6.18) for the >126 mg/dL serum glucose category (both compared to the <100 mg/dL category). In a subgroup analysis, the RR of serum glucose among those who were both HBsAg seronegative and non-drinkers was 4.46 (95% CI = 1.09-18.28) for those with glucose levels >100 mg/dL. Conclusions : The results of this study suggest that a high level of serum glucose can increase liver cancer risk independently of hepatitis infection and drinking history in Koreans. This study implies that glucose intolerance may be an independent risk factor for liver cancer.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.482-489
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• 2017

Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.

• Korea journal of population studies
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• v.6 no.1
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• pp.43-69
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• 1983

This study was conducted to make the life tables from specific causes of death in Korea. Both "Life tables of Korea in l978-79" and "the statistics on causes of death statistics in 1980" issued by Economic Planning Board were used as source of data for this study. Among the 58, 187 death certificates reported to the concerned authorities, 39, 801 causes were drawn for the purpose of this study. As a result, it is revealed that two thirds of men in Korea died from these 10 major causes of death. The summarized results are as follows: 1. According to recent statistics, 10 major causes of death in 1980 were shown in the order of 1) malignant neoplasms, 2) cerebrovascular disease, 3) accidents and adverse effects, 4)hypertensive disease, 5) ischaemic heart disease and heart attack, 6) chronic liver disease and cirrhosis, 7) tuberculosis, 8) pneumonia, bronchitis, emphysema and asthma, 9) suicide, 10) diabetes mellitis. 2. The major causes of death in Korea were very similar to those of developed countries such as West Germany, Denmark and Japan. This means that our pattern of death causes is almost approaching to that of developed countries. 3. Our crude death rate in 1980 was on the line of 6.6 per 1, 000 people. This is very low level, compared with 12.1 in West Germany and 10.0 in Denmark, however, our age sepcific death rate was on the verge of doubled level in each age category as to that of West Germany, Denmark and Japan. The fact tells us that our death rate is very high yet, especially in young and prime adult age, and the proportion of the aged is quite low. 4. Average ages of people died from malignant neoplasms, cerebro vascular diseases and hypertensive diseases were 63.1, 66.6, 67.3 respectively, however, that of accidents and adverse effect was only 42.5. This shows that accidents occur indifferently from age. 5. In the curve of eventual death probability, the curve of malignant neoplasms was the highest of all curves before 60 in age. However, the probability curve of eventually dying from accidents and adverse effects tends to decline with age. 6. In this study five life tables from major causes of death (four leading causes of death and of tuberculosis) were constructed for 1979. These life tables are reflecting accurately the effects of age distribution on the specific cause of death. In the surviving curje of these tables we can see that the curve of accidents is adversely related to age. While curves of neoplasms, hypertension and tuberculosis are not diminishing before 40 in age, they are going sharply downward after 50 in age.ard after 50 in age.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1297-1303
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• 2012

Aims: Primary hepatocellular carcinoma (HCC) is a common malignancy often related to hepatitis viral infection. Smad4 is known to mediate the TGF-${\beta}$ pathway to suppress tumorigenesis. However, the function of Smad4 in HCC is still controversial. In this study we compared levels of Smad4 in HCC tissues with or without hepatitis virus infection and adjacent normal-appearing liver. Methods: Samples from HCC patients were analyzed for Smad4 protein and mRNA expression by immunohistochemistry (IHC), RT-PCR and Western blotting. Results: We found that tumor tissues expressed less Smad4 mRNA and protein than the adjacent tissues. Most HCC tumor tissues were negative for Smad4 in IHC staining, while the majority of adjacent tissues were positively stained. Interestingly, protein levels were higher in HCC tissues with viral hepatitis than those without virus infection. Suppression of expression appeared closely related to HCC, so that Smad4 appears to function as a tumor suppressor gene (TSG). Conclusion: Patients with hepatitis viral infection, at higher risk for HCC, exhibited increased Smad4 protein expression suggesting hepatitis virus may modulate Smad4 expression, which is functionally distinct from its putative role as a TSG. Smad4 expression may thus be an applicable marker for diagnosis and/or a target to develop therapeutic agents for HCC.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.4
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• pp.268-275
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• 2015

Purpose: Primary sclerosing cholangitis (PSC) is a rare condition that can be associated with inflammatory bowel disease (IBD). The aim of this study was to evaluate PSC and its association with IBD in children. Methods: We retrospectively enrolled 13 pediatric patients (<18 years) with PSC treated at Asan Medical Center between June 1989 and December 2013. Clinical findings and long-term outcomes were investigated. During the same period, the incidence of PSC among IBD patients was evaluated among 600 Crohn disease (CD) and 210 ulcerative colitis (UC) patients. Results: All 13 study patients diagnosed with PSC also presented with IBD. Eleven boys and two girls with a median age of 15.0 years old (9.0-17.8 years) were included. The cumulative incidence of PSC for UC was 5.7% (12 of 210) and 0.2% for CD (1 of 600), respectively. PSC occurred during follow-up for IBD for five patients (38.5%) whereas, IBD developed during follow-up for PSC for two patients (15.4%), and was diagnosed during the initial work-up for PSC for 6 patients (46.2%). For the 77.3 month median follow-up period, 9/13 patients (69.2%), neither the clinical symptoms nor blood test results worsened. Two cases (15.4%) developed liver cirrhosis and underwent liver transplantation. Among 13 PSC patients with IBD, two (15.4%) developed colorectal cancer, and no one developed cholangiocarcinoma. Conclusion: All patients with PSC in this study had associated IBD. The incidence of PSC was not rare compared to reports in adults. PSC should be considered during the management of IBD and vice versa in children.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.350-356
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• 1994

Purpose : Hepatic arterial perfusion scintigraphy with Tc-99m-macroggregated albumin (HAPS) study was carried out in 16 patients with hepatocellular carcinoma(HCC) and in six patients without liver tumor to evaluate HAPS findings of hepatocellular carcinoma and usefullness of HAPS. Materials and Methods : HAPS with planar and SPECT study were performed in 22 patients after conventional hepatic or celiac arteriography. For HAPS study, 4-5 mCi of MAA mixed with 2ml of saline was injected into proper hepatic artery or its distal branches at the rate of approximately 1ml/sec. We analysed 21 HCCs over 2cm in diameter(average diameter; 6.4cm) and 17 of 21 HCCs were over 4cm in diameter(Table 1). CT, sonography and angiography were performed within two week in all 16 patients and liver scan was performed in 12 patients. Results : Three different pattern of tumor perfusion were observed in 16 patients with HCC (Table 2). 1) diffuse increased perfusion in 16 of 21(76%)(Fig. 1) 2) increased peripheral perfusion in 4 of 21(19%) (Fig. 2) 3) diffuse decreased perfusion in 1 of 21 (5%) Arteriovenous shunt indicated by lung uptake of MAA were observed in 9 of 16(56%)(Fig. 4). In contrast, angiography demonstrates arteriovenous shunt in 2 of 16(13%). There was no accumulation of radioactivity on RBC-blood pool scan in all six patients with HCC examined (Fig. 1). Conclusion : HAPS is useful study in evaluation of perfusion pattern or vascularity of HCC and in detection of arteriovenous shunt.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4727-4731
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• 2013

Background: There have been no large-scale population-based studies to estimate the subsequent risk of primary liver cancer (PLC) among patients with pyogenic liver abscess (PLA). This study aimed to provide relevant data. Materials and Methods: The Taiwan Longitudinal Health Insurance Database for the years 2000 and 2005 was used. The PLA group were adult inpatients who were newly diagnosed with PLA from 2000 to 2008. The control group was randomly selected and matched with the PLA group in terms of age, sex, and date in which medical treatment was sought other than for PLA. Results: There were 1,987 patients each in the PLA and control groups. In total, 56 had PLC, 48 (2.4%, 601.5 per 100,000 person-years) from the PLA group, and 8 from the control group. After adjusting for potential covariates, the hazard ratio of PLC for the PLA group was 3.4 times that of the control group (95% confidence interval = 1.6-7.3, p <0.001). The PLC risk for the PLA group was significantly higher within the first year after PLA diagnosis (hazard ratio: 35.4) as compared with the control group and became insignificant (hazard ratio: 2.0, 95% confidence interval = 0.8-4.9) more than one year after PLA diagnosis. Conclusions: Patients with PLA have a higher rate of PLC than matched controls, especially within the first year after the diagnosis of PLA, suggesting PLA is a warning sign for PLC.

• Journal of Digestive Cancer Research
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• v.1 no.2
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• pp.104-107
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• 2013

Gallbladder (GB) cancer is highly malignant neoplasm found in advanced stage and chemotherapy commonly plays a palliative role in GB cancer. We report a case of unresectable GB cancer treated with chemotherapy followed by extended cholecystectomy. Fifty-six-year-old male visited our hospital with weight loss and dyspnea on exertion. Computed tomography detected pulmonary embolism and diffuse GB wall thickening with para-aortic lymph node enlargement. The length of common channel was 23mm at magnetic resonance cholangiopancreatography which stands for anomalous union of the pancreaticobiliary duct. Anticoagulation was started for pulmonary embolism. GB wall mass was regarded as unresectable GB cancer with distant lymph node metastasis. Gemcitabine and cisplatin combination chemotherapy was carried out for 6 cycles. Primary tumor was stationary but multiple enlarged lymphnodes were almost completely disappeared. Extended cholecystectomy with hepaticojejunostomy was performed. Post-operative tumor stage was T3N1 (stage IIIB) and R0 resection was achieved. After operation he has no evidence of disease recurrence for 6 months.