Serum uric acid and chronic kidney disease: the Severance cohort study.

BACKGROUND: Both serum uric acid (SUA) and chronic kidney disease (CKD) are associated with the risk of cardiovascular disease; however, it is unclear whether SUA independently increases the risk of CKD based on longitudinal data. METHODS: To investigate the relationship between SUA levels and CKD development, we initiated a 10.2-year prospective cohort study. Data from 14 939 Koreans, 20-84 years of age, who completed a questionnaire and medical examination at the Severance Health Promotion Center were evaluated. The outcome of interest, CKD, was defined as an estimated glomerular filtration rate (GFR) of <60 mL/min/1.73m(2) via the simplified Modification of Diet in Renal Disease equation. RESULTS: A multivariate Cox proportional hazard model, controlling for age, life style and other cardiovascular risk factors, showed an increased risk of developing CKD for men [hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.9] and women (HR = 1.3; 95% CI = 1.0-1.8) in the highest quartiles of SUA compared to their counterparts in the lowest quartiles. The relationship between SUA and CKD was linear and stepwise in men. The HRs for renal function Grade 2 (75-89.9 mL/min/1.73m(2)), Grade 3 (60-74.9 mL/min/1.73m(2)) and Grade 4 (<60 mL/min/1.73m(2)) increased with an increase in SUA quartiles as compared to the baseline GFR group (Grade 1, ≥90 mL/min/1.73m(2)). CONCLUSIONS: Higher SUA levels increased the risk of CKD, suggesting that at least part of the reported association between SUA and cardiovascular disease may be connected to CKD.

Telbivudine versus lamivudine in patients with chronic hepatitis B.

BACKGROUND: Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B. METHODS: In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. RESULTS: At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7% vs. 56.3%, P=0.01); telbivudine also was not inferior to lamivudine for these end points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients, telbivudine was superior to lamivudine with respect to the mean reduction in the number of copies of HBV DNA from baseline, the proportion of patients with a reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of resistance to the drug. Elevated creatine kinase levels were more common in patients who received telbivudine, whereas elevated alanine aminotransferase and aspartate aminotransferase levels were more common in those who received lamivudine. CONCLUSIONS: Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine. (ClinicalTrials.gov number, NCT00057265 [ClinicalTrials.gov].).

Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection.

BACKGROUND: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence. PATIENTS AND METHODS: We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow-up), fluctuating DNA (cut-off value: 100,000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non-viraemia group) had consistently negative DNA (<100,000 copies/ml), while 68 (viraemia group) had consistently positive DNA (>100 000copies/ml). Serum DNA level, biochemical tests, alpha-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery. RESULTS: There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow-up duration between the two groups. During follow-up (median: 35 months), patients in the non-viraemia group had a lower 5-year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P=0.043). In multivariate analysis, sustained viraemia (P=0.041) increased recurrence independently. CONCLUSIONS: Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA.

Combination therapy of thymosin alpha-1 and lamivudine for HBeAg positive chronic hepatitis B: A prospective randomized, comparative pilot study.

BACKGROUND AND AIM: Monotherapy of lamivudine, interferon-alpha (IFN-alpha), and thymosin alpha-1 (Talpha1) is unlikely to be sufficient for the eradication of a chronic hepatitis B virus (HBV) infection. The aim of our study is to elucidate whether the combination of Talpha1 and lamivudine is superior to lamivudine monotherapy in hepatitis B e antigen (HBeAg) positive naïve patients with chronic hepatitis B. METHODS: Sixty-seven patients were assigned to two different groups in a randomized manner. The combination group (n = 34) received Talpha1 (1.6 mg subcutaneously, twice a week) and lamivudine (100 mg orally, daily) for 24 weeks, followed by continuous lamivudine therapy. The monotherapy group (n = 33) received lamivudine monotherapy continuously. RESULTS: The incidence of HBeAg seroconversion at 24 weeks was 26.5% (9/34) in the combination group and 6.1% (2/33) in the monotherapy group (P = 0.024). However, there was no statistically significant difference between 26.5% (9/34) in the combination group and 12.1% (4/33) in the monotherapy group at 52 weeks (P = 0.138). The emergence of viral breakthrough gradually increased to 35.3% (12/34) in the combination group, and to 21.2% (7/33) in the monotherapy group at 52 weeks (P = 0.201). CONCLUSIONS: The combination treatment of Talpha1 and lamivudine did not have an obvious benefit of virological and biochemical response as compared to the lamivudine monotherapy during the combination period. In addition, after the cessation of Talpha1 treatment, the combination therapy did not prevent the occurrence of viral and biochemical breakthroughs.

Changes in serum and ascitic monocyte chemotactic protein-1 (MCP-1) and IL-10 levels in cirrhotic patients with spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis (SBP) is a prototypical infectious disease of cirrhotic patients. It has been suggested that cirrhotic patients' response to infection is less effective because of differences in the inflammatory and immune reactions. This study aimed to investigate the expression of the inflammatory cytokines monocyte chemotactic protein-1 (MCP-1) and interleukin-10 (IL-10) in cirrhotic patients with SBP. The MCP1 and IL-10 levels in the sera and ascitic fluids of cirrhotic patients with (n = 40) or without SBP (n=17) were serially analyzed by ELISA. In the non-SBP group, the mean MCP-1 levels in sera and ascites were 53.0 +/- 45.8 pg/mL and 197.5 +/- 109.5 pg/mL, respectively, and the IL-10 levels were 10.9 +/- 9.5 pg/mL and 77.6 +/- 79.7 pg/mL, respectively. In the SBP group, the mean MCP-1 levels in serum and ascites before treatment were 164.7 +/- 126.4 pg/mL and 365.3 +/- 583.0 pg/mL, respectively, and the IL-10 levels were 31.4 +/- 44.1 pg/mL and 188.1 +/- 189.5 pg/mL, respectively. The sera MCP-1 and ascites IL-10 levels differed significantly between the two groups. In the SBP group, sera and ascitic MCP-1 and IL-10 levels fell during treatment. The low MCP-1 and IL-10 levels on the seventh day of treatment were found to have a statistically significant relationship to patient survival. MCP-1 and IL-10 levels in sera and ascites may be related to the clinical course of SBP.

Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma.

PURPOSE: The purpose of this study was to evaluate the long-term tumor response after phase IIb clinical study and the safety of percutaneous holmium-166 ((166)Ho)/chitosan complex injection (PHI) therapy for small hepatocellular carcinoma as a local ablative treatment. (166)Ho is a radioactive isotope derived from natural holmium-165. We developed a (166)Ho/chitosan complex (Milican, Dong Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the radioactive material within the tumor. EXPERIMENTAL DESIGN: Forty patients with single hepatocellular carcinoma < 3 cm in maximal diameter were enrolled in this study. The patients either had refused surgery or were poor surgical candidates and were treated with only single session of PHI. RESULTS: Two months after PHI, complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with hepatocellular carcinoma lesions < 3 cm and in 11 of 12 patients (91.7%) with hepatocellular carcinoma < 2 cm. Tumors recurred in 28 patients during the long-term follow-up period, of which 24 recurred at another intrahepatic site. The 1-year and 2-year cumulative local recurrence rates were 18.5% and 34.9%, respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and 65.3%, respectively. Transient bone marrow depression was serious adverse event requiring hospitalization in two patients. CONCLUSIONS: PHI was found to be a safe and novel local ablative procedure for the treatment of small hepatocellular carcinoma and could be used as a bridge to transplantation. A phase III randomized active control trial is clearly warranted among a larger study population.

[The efficacy and safety of telbivudine in korean patients with chronic hepatitis B].

BACKGROUND AND AIMS: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. METHODS: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. RESULTS: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. CONCLUSIONS: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.

[Clinical features and treatment outcome of advanced hepatocellular carcinoma with inferior vena caval invasion or atrial tumor thrombus].

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) with an extension to the inferior vena cava (IVC) or right atrium is uncommon, and its prognosis remains unclear due to the few case reports. In order to elucidate the natural history and treatment outcome, this study investigated advanced HCC patients with an IVC invasion or atrial tumor thrombus. METHODS: Between November 1987 and June 2004, a total of 41 patients were diagnosed as having HCC with IVC or right atrial involvement using the new imaging techniques including a two-dimensional echocardiography. Those patients were stratified into the untreated 'control group' (n=17) and 'treated group' (n=24). The clinical features, treatment outcome and prognosis including patient survival were analyzed. RESULTS: The mean age of the total patients was 55 years (male:female, 33:8). The most common cause of HCC was a hepatitis B virus infection (85.4%), followed by a hepatitis C virus infection (7.4%). According to the Child-Pugh classification, 24 patients were Child-Pugh class A (58.5%), 15 were Child-Pugh class B (36.6%), and 2 were Child-Pugh class C (4.9%). Lung metastases were identified in 10 patients (24.5%). The treatment modalities of the treated group included 11 systemic chemotherapy regimens (5-FU and cisplatin), 10 transarterial chemotherapy regimens, 2 chemoradiation procedures and 1 hepatic resection. The overall survival was 3.0 months (range, 1-29 months). The 6 month survival rate was 23.5% (4/17) in the control group and 29.2% (7/24) in the treated group. The 12 months survival rate was 0% (0/17) and 25.0% (6/24), respectively. Independent prognostic factor affecting the survival was whether or not any treatment had been carried out. CONCLUSIONS: Although the prognosis of advanced HCC with IVC invasion or a right atrial tumor thrombi is poor, treatment might improve the survival rate.

The clinical impact of early detection of the YMDD mutant on the outcomes of long-term lamivudine therapy in patients with chronic hepatitis B.

The early emergence of lamivudine (3TC)-resistant tyrosine-methionine-aspartate-aspartate (YMDD) mutants has been reported during 3TC therapy in patients with chronic hepatitis B (CHB) in hepatitis B virus (HBV)-endemic areas; however, its clinical impact during long-term 3TC therapy is unknown. This study was performed to investigate the impact of the early emergence of YMDD mutants 3 months after the initiation of treatment on the outcomes of long-term 3TC therapy in HBV e antigen (HBeAg)-positive CHB. We analysed YMDD genotypes in consecutive samples from 30 patients with HBeAg positive CHB throughout 3TC treatment using both restriction fragment length polymorphism and mass spectrometric assays. Long-term outcome was compared between patients who had YMDD mutations detected at 3 months and those who had no mutations. YMDD mutation was detected in 16 (53.3%) out of 30 patients at 3 months and only the rtM2041 mutation was found. Cumulative HBeAg loss rates at 3 years was 12.5% and 57.4% in patients who had the rtM2041 mutant and wild-type virus at 3 months, respectively (P=0.010). Cumulative viral breakthrough rates at 3 years was 75.0% and 14.3% in patients who had the rtM204I mutant and wild-type virus at 3 months, respectively (P=0.002). Logistic regression revealed that YMDD mutation at 3 months was significantly related to viral breakthrough within 24 months (P=0.003). In conclusion, early detection for HBV YMDD mutation at 3 months may be useful to predict the long-term outcomes of 3TC therapy in patients with HBeAg-positive CHB in HBV-endemic areas.

Efficacy and long-term follow up of combination therapy with interferon alpha and ribavirin for chronic hepatitis C in Korea.

Combination therapy with interferon alpha (IFN-alpha) and ribavirin for 24 or 48 weeks according to HCV genotype has improved the overall sustained virological response (SVR) rates to approximately 40%. The aim of this study was to investigate the long-term efficacy of combination therapy with IFN-alpha and ribavirin for chronic hepatitis C in Koreans. One hundred thirty-eight patients with chronic hepatitis C who received this combination therapy between 1995 and 2003 were analyzed retrospectively. All patients were treated with IFN-alpha 3-6 million units three times weekly in combination with 900-1200 mg/day of ribavirin for 24 weeks. The overall SVR rate was 41.3%. Patients were followed up for a median of 41 months (range, 12-105 months) after completion of therapy. In all of the SVR patients (57 patients), SVR was conserved during the follow-up period. None of the patients progressed to decompensated liver disease or hepatocellular carcinoma (HCC). However, 5 of the 81 non-SVR patients (6.2%) progressed to decompensated liver disease or HCC. In conclusion, combination therapy with IFN-alpha and ribavirin shows good long-term efficacy in patients with chronic hepatitis C in Korea, one of the highest endemic areas of hepatitis B virus (HBV) infection.

[Natural history of HBeAg negative chronic hepatitis B virus infection: a cohort study].

BACKGROUND/AIMS: The long-term virologic and biochemical changes in patients with HBeAg negative HBV infection, especially in Asia, remain unclear. To address this issue, we conducted a 3 year- retrospective, cohort study. METHODS: A total of 157 patients with HBeAg negative HBV infection who were monitored without treatment were reviewed between January 1999 and March 2004. Those patients were followed up every 3 months with liver function tests and serologic tests. All patients were stratified into 3 groups; inactive carrier (IC), viremic carrier (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization assay (sensitivity: 1.4 x 10(5)) genomes/mL, Digene Diagnostics, Silver Spring, USA). RESULTS: The median age of enrolled patients was 42.7 years (M:F=2.3:1). By single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over time (P=0.002) and transition rates among three groups after 3 years of follow-up are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a disease state in the middle of transition from IC to CH. CONCLUSIONS: We demonstrated the dynamic changing patterns of HBeAg negative CH with time, of which the change from IC or VC to CH was dominant.

Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study.

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p = 0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0 --> 4.2, p = 0.000); lactulose group (11.3 --> 5.0, p = 0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

[Clinical outcome of pulmonary resections in patients with pulmonary metastasis of hepatocellular carcinoma].

BACKGROUND/AIMS: Although the lung is the most common site of extrahepatic spread from hepatocellular carcinoma (HCC), the role of surgery for pulmonary metastasis remains unclear. The aim of this study was to evaluate the efficacy of pulmonary resection in patients with pulmonary metastasis from HCC. METHODS: Between July 2000 and July 2004, a total of 6 patients with pulmonary metastasis from HCC underwent curative pulmonary resections. The patients were divided into two groups (Surgery group and Non-surgery group) according to the primary treatment modality of HCC. Medical records, imaging studies, and pathologic reports of the surgical specimens were reviewed. RESULTS: Three patients in the surgery group underwent pulmonary resections for a solitary metastasis after hepatectomy for HCC, and they are all still alive. One of the 3 patients developed a tumor recurrence in the chest wall after pulmonary resection. The survival time after diagnosis of HCC were 79, 122, and 54 months, respectively. The survival time after pulmonary metastatectomy were 49, 39, and 20 months in the three patients. Another 3 patients in the non-surgery group, received a pulmonary metastatectomy; they had either a complete response HCC or partial radiologic response. These 3 patients developed recurrent disease in the liver. One of 3 patients died. The survival time after diagnosis of HCC were 153, 83, 12 months. The survival time after pulmonary metastatectomy were 51, 4, 2 months. CONCLUSIONS: The surgical resections of a solitary pulmonary metastasis from HCC in highly selected patients might be an effective treatment modalities for prolonged survival.

[HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy].

BACKGROUND/AIMS: Viral suppression of the hepatitis B virus (HBV) can be induced by lamivudine, but the relapse seen in many patients after cessation of lamivudine therapy is troublesome. We thought that the host immune response is important to prevent viral relapse. We compared the frequency of HBV-specific CD8+ T cells in the peripheral blood and their expansion capacity after exposure to viral antigen between the patients showing sustained HBeAg seroconversion after use of lamivudine and those patients without sustained response. METHODS: We analyzed HBV-specific CD8+ T cells that were isolated from the blood of 14 patients with HLA-A2 who showed lamivudine induced HBeAg seroconversion (HBV DNA < 0.5 pg/mL, and the cells were negative for HBeAg) at the end of lamivudine therapy. The purified T cells were directly stained ex vivo, after they had been stimulate with synthetic peptide, using the HBV core 18-27-specific HLA tetramer (Tc 18-27) and monoclonal antibody to CD8. The HBV viral load was quantified by the Amplicor HBV Monitor assay. RESULTS: In patients with a sustained HBeAg response (the sustained group) for a duration of 15.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 49.5 (15-135). On the contrary, in patients who experienced relapse (the relapsed group) during a median of 7.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 13.5 (0-95). Especially, among patients with a viral load of HBV DNA < 1 X 10(3) copies at the end of treatment, the median number of Tc 18-27 cells out of 5 X 10(4) CD8+ T cells was 87 (45-135) in sustained group compared to 12 (6-50) in the relapsed group. All patients in the sustained group demonstrated a vigorous expansion of the core 18-27-specific CD8+ T cells after stimulation with viral peptide, in contrast to only 3 out of 8 patients in the relapsed group. CONCLUSIONS: This study demonstrates that the frequency and functional responsiveness of the circulating HBV-specific CD8+ T cells may be important for obtaining a sustained HBeAg response to lamivudine.

[Efficacy of repeated hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma with portal vein tumor thrombosis].

BACKGROUND/AIMS: The aim of this study is to elucidate the efficacy of repeated hepatic arterial infusion chemotherapy (HAIC) and different chemotherapeutic regimens for treating patients having advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS: From Jan. 1999 and Dec. 2003, a total of 103 patients diagnosed as having HCC with PVTT, but without extrahepatic spreading, were enrolled in this study. They were stratified into two groups. Group I (67 patients) received intraarterial cisplatin (CDDP, 80 mg/m2 for 2 hours on Day 1), Group II (36 patients) received intraarterial CDDP (60 mg/m2 for 2 hours on Day 2) and 5-fluorouracil (5-FU, 500 mg/m2 for 5 hours on Day 1-3). They were scheduled to receive at least three consecutive courses of the HAIC at 1 month intervals. RESULTS: Among the 66 patients who completed the protocol, one (2.5%) and seven (17.5%) patients of group I, and one (3.8%) and four (15.4%) of group II, exhibited complete and partial responses, respectively. The median survival period of all the patients was 6 months. Group II showed a tendency to improve the median survival compared to group I (8.5 vs 5.0 months, respectively, P=0.45). The most common adverse reaction was nausea (58.2%). However, an elevation of the total bilirubin level was more frequent in Group I than in Group II (61.3% vs 20.7%, respectively, P<0.05). CONCLUSIONS: Repeated HAIC using CDDP achieved favorable results in a few patients with HCC with PVTT, and additional 5-FU may be useful.

Dose-response relationship in local radiotherapy for hepatocellular carcinoma.

PURPOSE: Dose escalation using three-dimensional conformal radiotherapy (3D-CRT) is based on the hypothesis that increasing the dose can enhance tumor control. This study aimed to determine whether a dose-response relationship exists in local radiotherapy for primary hepatocellular carcinoma (HCC). METHODS AND MATERIALS: One hundred fifty-eight patients were enrolled in the present study between January 1992 and March 2000. The exclusion criteria included the presence of an extrahepatic metastasis, liver cirrhosis of Child class C, tumors occupying more than two-thirds of the entire liver, and a performance status on the Eastern Cooperative Oncology Group scale of more than 3. Radiotherapy was given to the field, including the tumor, with generous margin using 6- or 10-MV X-rays. The mean radiation dose was 48.2 +/- 7.9 Gy in daily 1.8-Gy fractions. The tumor response was assessed based on diagnostic radiologic examinations, including a computed tomography scan, magnetic resonance imaging, and hepatic artery angiography 4-8 weeks after the completion of treatment. Liver toxicity and gastrointestinal complications were evaluated. RESULTS: An objective response was observed in 106 of 158 (67.1%) patients. Statistical analysis revealed that the total dose was the most significant factor associated with the tumor response. The response rates in patients treated with doses <40 Gy, 40-50 Gy, and >50 Gy were 29.2%, 68.6%, and 77.1%, respectively. Survivals at 1 and 2 years after radiotherapy were 41.8% and 19.9%, respectively, with a median survival time of 10 months. The rate of liver toxicity according to the doses <40 Gy, 40-50 Gy, and >50 Gy was 4.2%, 5.9%, and 8.4%, respectively, and the rate of gastrointestinal complications was 4.2%, 9.9%, and 13.2%, respectively. CONCLUSIONS: The present study showed the existence of a dose-response relationship in local radiotherapy for primary HCC. Only the radiation dose was a significant factor for predicting an objective response. The results of this study showed that 3D-CRT can theoretically be used for treating primary HCC.

Low grade gastric mucosa associated lymphoid tissue lymphoma: treatment strategies based on 10 year follow-up.

AIM: To deduce strategic guidelines of gastric mucosa associated lymphoid tissue lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to various treatment modalities. METHODS: A total of 55 patients with MALTOMA from May 1992 to August 2002 were retrospectively reviewed. RESULTS: Complete remission was obtained in 24 (82.8%) of 29 patients treated with anti Helicobacter pylori (H pylori) regimen only. The duration to reach complete remission was 12 months (85 percentile, 2-33 months). Five patients showed complete remission with radiation therapy (26-86 months). Two of them were H pylori treatment failure cases. CONCLUSION: H pylori eradication is an effective primary treatment option for low grade MALTOMA and radiation therapy could be considered in patients with no evidence of H pylori infection or who do not respond to H pylori eradication therapy 12 months after successful eradication.

Treatment outcome of transcatheter arterial chemoinfusion according to anticancer agents and prognostic factors in patients with advanced hepatocellular carcinoma (TNM stage IVa).

Transcatheter arterial chemoinfusion (TACI) is the main treatment modality for advanced hepatocellular carcinoma (HCC). However, the therapeutic efficacy of TACI according to anti-cancer agents and prognostic factors for advanced HCC (TNM stage IVa) has not been previously clarified. A total of 127 patients with TNM stage IVa HCC were divided into intra-arterial Adriamycin (Group I) and intra-arterial Cisplatin (Group II) infused groups, according to the anticancer agents that were used. We compared the therapeutic efficacy of TACI applied anticancer agents, and we also analyzed the prognostic factors which influenced the survival rates. Chi-square test, t- test, Cox's proportional hazard regression model, and Kaplan- Meier method were performed. The overall survival was significantly different (10.0 vs 5.7 months, respectively) and the results favored Group I. On univariate analysis, the significant prognostic factors included age, portal vein thrombosis (PVT), tumor size (diameter > 5 cm), type of tumor, the reduction rate (tumor size and alpha- fetoprotein) after 3 months of chemotherapy, serum albumin level, serum alkaline phosphatase level and total serum bilirubin levels at the time of diagnosis. After repeated chemotherapy, Group I showed better survival (14.0 vs 7.9 months). However, there was no statistical difference in the survival rate of the two groups for cases involving large tumors, PVT and diffuse type of HCC. Group I showed better survival than Group II. However, when the other prognostic factors were taken into consideration, there was no significant difference in the survival rate of the two groups, except for the cases with small or nodular HCC.

Total necrosis of hepatocellular carcinoma due to spontaneous occlusion of feeding artery.

Spontaneous total necrosis of hepatocellular carcinoma is extremely rare, with only 15 cases reported to date in the English literature, and the involved mechanism remains unresolved. This paper describes a case of spontaneous necrosis of hepatocellular carcinoma in a 70-year-old man with chronic hepatitis. The patient suffered epigastric pain on admission and computed tomography revealed a 4 cm mass with low density in the left lobe of the liver. Fine needle aspiration biopsy revealed a few scattered, naked and irregular nuclei exhibiting nuclear hyperchromasia in the dirty necrotic background, a finding highly suggestive of malignancy. The lobectomized liver revealed a 3.5 cm, well encapsulated, round, and nearly totally necrotic mass. On microscopic examination, the tumor was found to be composed of thick trabeculae of necrotic tumor cells, supporting the diagnosis of hepatocellular carcinoma. After surgery and throughout 13 months of follow up the patient has recovered well.

[Changes of ascites nitric oxide according to the treatment course in cirrhotic patients with spontaneous bacterial peritonitis].

BACKGROUND/AIMS: Nitric oxide (NO) is a molecule involved in vascular dilatation and pathogen suppression. It also has immunologic and regulatory functions. Liver cirrhosis is characterized by an increased risk for bacterial infections, including spontaneous bacterial peritonitis (SBP). The role of NO in SBP which develops in cirrhosis has not been clearly established. The aim of this study was to investigate the role of NO in the pathogenesis of SBP and its clinical usefulness for prediction of disease prognosis. METHODS: This study was designed to investigate the changes of ascites NO in the course of treatment. Nitric oxide metabolite (nitrites+nitrates [NOx]) was measured by chemiluminescence in 84 ascites samples obtained from 84 cirrhotic patients. Among them, the 38 patients with SBP were treated with cefotaxime 2.0 g, q 12hr for 7 days. In 24 of SBP patients, ascites was obtained consecutively before treatment (day 0), during treatment (day 2), and after treatment (day 7). RESULTS: Ascites NO levels in the patients with SBP (n=38; 82.3 +/- 14.4 microM) were not different from those in patients with sterile ascites (n=46; 54.6 +/- 13.0 microM). There was no significant change of NO levels in sequential ascites samples during antibiotic treatment. Ascites NO level before treatment was significantly higher in SBP patients who responded to antibiotics (n=26; 101.86 microM/L) than that in SBP patients who did not respond to antibiotics (n=12; 40.03 microM/L, P=0.044). A significant direct correlation was found between ascites and serum NO levels before treatment (Pearson correlation, r2=0.86, P=0.001). Among the SBP patients, treatment response rate to antibiotics were significantly higher in those patients with pretreatment NO level > or = 80 microM/L in multivariate analysis. CONCLUSIONS: Ascites NO level was not different between ascites from SBP patients and ascites from cirrhotic patients with sterile ascites. There were no changes of ascites NO in SBP patients during treatment. Therefore ascites NO was not useful to predict the progress of SBP. Ascites NO levels reflect serum NO levels, and the patients with higher NO level may have better response to antibiotics.