Byung Kyu Park

Long-term outcome of chronic hepatitis B based on histological grade and stage

Background and Aim:  This study evaluated the long‐term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage.

Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer

Background:  The aim of this phase II study was to determine the efficacy of gemcitabine plus cisplatin chemotherapy in patients with advanced biliary tract cancer.

The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma

Objectives:Vascular endothelial growth factor-C (VEGF-C) is known to be an important lymphangiogenetic factor. Lymphatic spread is a key prognostic factor in intrahepatic cholangiocarcinoma (ICC). We studied the expression of VEGF-C in ICC tissues to clarify its clinicopathologic significance. Methods:The expression of VEGF-C in surgical specimens obtained from 36 patients with ICC who underwent hepatic resection was examined by immunohistochemistry and Western blotting. Strong staining was defined as the presence of VEGF-C immunoreactivity in at least 50% of the tumor cells. Immunoreactivity in ∼10% to ∼50% of the tumor cells was considered as weak staining, and less than 10% as no staining. Results:Of the 36 patients with ICC, 15 patients (41.7%) showed a strong positive result for VEGF-C. Eleven cases (30.6%) were negative and 10 cases (27.8%) showed weak immunoreactivity. VEGF-C expression was significantly correlated with lymph node metastasis (P = 0.032) and positive surgical margin (P = 0.03). Patients who had strong positive staining for VEGF-C showed significantly less favorable survival rates compared with patients who had negative or weak staining (P < 0.01). Other significant prognostic factors by univariate analysis were vascular invasion, lymph node involvement, and positive surgical margin. Multivariate analysis demonstrated that strong VEGF-C expression (P = 0.028) and vascular invasion (P = 0.021) were independent factors indicating poor prognosis. Conclusions:Our data suggest that VEGF-C expression serves as an independent and important prognostic factor in ICC patients, and it may play an important role in the lymph node metastasis of ICC.

Bile Acid Analysis in Biliary Tract Cancer

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin ≤ 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.

Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with chronic hepatitis B

Goals We aimed to determine whether the presence of large liver cell dysplasia (LLCD) and/or small LCD (SLCD) in chronic hepatitis B is a risk factor for hepatocellular carcinoma (HCC) development. Background A close relationship between LLCD/SLCD and hepatitis B virus has been observed and SLCD has been proposed to be a putative precursor of HCC, whereas the significance of LLCD is still controversial. Study One hundred eighty-one patients with chronic hepatitis B who underwent needle liver biopsy were evaluated for the presence of LLCD/SLCD. The predictive value of LLCD/SLCD for HCC development was assessed. Results LLCD and SLCD were present at initial biopsy in 82 (45%) and 17 (9%) patients, respectively. During the mean follow-up of 115±48 months, 19 (10%) cases were diagnosed of HCC, of which 13 (76%) and 3 (17%) cases had demonstrated LLCD and SLCD, respectively, at initial evaluation. The patients with LLCD showed a significantly higher cumulative probability of HCC development than those without LLCD (P=0.016). The risk of HCC development in the presence of LLCD was approximately 3-fold, with positive and negative predictive values of 15.9% and 94.9%, respectively. The patients with SLCD showed no significant difference in cumulative probability of HCC development compared with those without (P>0.05). Conclusions LLCD in chronic hepatitis B is considered to be one of the risk factors for HCC development and its presence may help to identify a high-risk subgroup of patients requiring more intensive screening for HCC.

The Relationship of Anatomic Variation of Pancreatic Ductal System and Pancreaticobiliary Diseases

The aims of this study were to identify the morphological diversities and anatomical variations of pancreatic ductal system and to define the relationships between pancreatic ductal systems, pancreaticobiliary diseases, and procedure-related complications, including post-ERCP pancreatitis. This study included 582 patients in whom both pancreatic duct (PD) and common bile duct were clearly visible by ERCP. PD systems were categorized into four types according to the relationship between common bile duct and PD. In types A and B, Wirsung duct formed the main PD. In type C, Wirsung duct did not form the main PD. If PD system did not fall into any of these three types, it was categorized as type D. The distribution of types among pancreatic ducts examined was as follows: type A: 491 cases (84.4%), type B: 56 cases (9.6%), type C: 20 cases (3.4%), and type D: 15 cases (2.6%). The anomalous anatomic variations of PD systems were divided into migration, fusion, and duplication anomalies. PD anomalies were noted in 51 patients, of which 19 (3.3%) were fusion anomalies (12 complete pancreas divisum, 7 incomplete pancreas divisum), and 32 (5.5%) were duplication anomalies (5 number variations, 27 form variations). No significant relationships between various PD morphologies and pancreaticobiliary diseases were found. However, post-ERCP hyperamylasemia was more frequently found in types C (41.7%), D (50%) and A (19.8%) than in type B (9.4%). In summary, whether Wirsung duct forms the main PD and the presence or absence of the opening of the Santorini duct are both important factors in determining the development of pancreatitis and hyperamylasemia after ERCP.

Efficacy of adefovir dipivoxil in the treatment of lamivudine-resistant hepatitis B virus genotype C infection.

Background and Aims: Adefovir dipivoxil (ADV) is a nucleotide analogue that is known to be effective for lamivudine‐resistant hepatitis B virus (HBV) mutants as well as wild‐type HBV. The aim of this study is to assess the efficacy of ADV against lamivudine‐resistant genotype C HBV mutants.

Comparison of Reaction Times of Ankle Joint Muscles in the Elderly Men and Women

Abstract: Elderly women are reported to have greater risk of falls. The purpose of this paper was to investigate thepossible gender differences in the reaction performance of ankle joint muscles, which have dominant role in the controlof sagittal plane balance. Twenty-six elderly men and women with comparable mean age participated in this study.Reaction times to the audible beeps were measured in the tibialis anterior muscle and gastrocnemius muscle. Reactiontime variables included premotor time, electromechanical delay and total reaction time. Gender difference in each reac-tion time was investigated by independent t-test. In both muscles, premotor time was longer in men but the elec-tromechanical delay was longer in women (p < 0.05). Resulting total reaction time was longer in men in tibialis anteriormuscle (p < 0.01) and it tended to be longer in men also in gastrocnemius muscle (p = 0.25). The results demonstratesthat the overall reaction performances of elderly women is better than or comparable to those of elderly men in anklejoint muscles. This suggests that the reaction performance of ankle muscles is hardly the cause of the greater riskof falls in elderly women. Key words: Reaction time, Ankle joint, Gender difference, Risk of falls

Age-gender differences in the postural sway during squat and stand-up movement.

Incidence of falling among elderly female has been reported to be much higher than that of elderly male. Although the gender differences in the elderly were reported for the static postural sway, there has been no investigation of the gender difference for the dynamic postural sway. This study investigates how age and gender affect the postural sway during dynamic squat and stand-up movement. 124 subjects (62 subjects for each of young and elderly) performed consecutive squat and stand-up movement, 2 times in one session, and 2 sessions per subject. Center of pressure (COP) was measured using force platform during the test. Outcome measures included peak-to-peak sways of the COP (COP sway) in the sagittal plane (anteroposterior) and frontal plane (mediolateral) and also those normalized by body height. Two-way ANOVA and post-hoc comparisons were performed for the outcome measures with the independent factors of age and gender. All outcome measures, excluding mediolateral COP sway, showed significant interaction of age and gender (p<0.05). Post-hoc test revealed that only female showed increase in COP sway with age. When normalized by height, increase in COP sways (both directions) with age significant only in women resulted in greater sways in elderly female than elderly male. This may be related to the greater fall rate of elderly female than that of elderly men while performing dynamic activities.

Adefovir plus Entecavir Therapy in Chronic Hepatitis B Patients with Treatment Failure to Lamivudine-Entecavir Sequential Therapy: Outcome at 2 Years

The efficacy of adefovir add-on therapy in treatmentexperienced patients with chronic hepatitis B (CHB) is debatable. This study aimed to evaluate the efficacy of adefovir add-on therapy in CHB patients with antiviral resistance to lamivudine/entecavir sequential therapy. CHB patients who exhibited documented resistance to lamivudine and switched to entecavir 1.0 mg monotherapy were evaluated and 19 of them showed active viral replication (HBV DNA levels ≥ 10⁵ copies/mL) or a history of treatment failure to lamivudine/ entecavir sequential therapy. Adefovir 10 mg/day has been added to these 19 patients and the virologic parameters were monitored every three months for 96 weeks. A primary responder was defined as patient who had a decline in serum HBV DNA ≥ 1 log10 copies/mL after 12 weeks of therapy, compared with the pretreatment value. In 19 CHB patients, 10(52.6%) patients were HBeAg positive, 7 (36.8%) had cirrhosis. The mean duration of previous entecavir therapy was 84.4 ± 22.5 weeks. The mean HBV DNA levels and ALT at baseline were 6.17 ± 0.96 log10 copies/mL, 53 ± 35 IU/L. The reduction of serum HBV DNA levels from baseline was 2.27 ± 1.34, 2.77 ± 1.41, and 3.09 ± 1.37 log10 copies/mL, at 24, 48 and 96 weeks, respectively. The rate of undetectable serum HBV DNA was 10.5% (2/19), 26.3% (5/19), and 31.5% (6/19) and ALT levels were normalized in 5 (55.6%), 6(66.7%), and 6(66.7%) of 9 patients with elevated ALT at baseline. Initial HBV DNA level was the only independent factor that was inversely associated with serum HBV DNA negativity at 96 weeks. Among 7 primary non-responders, 6 patients achieved serum HBV-DNA level < 4 log10 copies/mL at 96 weeks. Until 96 weeks, viral breakthrough was not detected in 19 patients. The adefovir add-on therapy may be helpful, even if not sufficient enough, for CHB patients with antiviral resistance to lamivudine/entecavir sequential therapy.