[Unresectable combined hepatocellular-cholangiocellular carcinoma treated with transcatheter arterial chemoembolization and gemcitabine: a case study].

A 76-year-old female was referred to our hospital because of liver dysfunction. Abdominal contrasted computed tomography (CT) revealed a tumor of 7.5cm in the hepatic hilar area. Based on the biopsy, the tumor was diagnosed by as combined hepatocellular-cholangiocellular carcinoma (with stem-cell features). The tumor was considered unresectable;hence, the patient underwent transcatheter arterial chemoembolization (TACE). However, a CT scan revealed the treatment to be ineffective. Subsequently, systemic gemcitabine (GEM) chemotherapy was administered and tumor shrinkage was observed with reperfusion of the umbilical portion of the left portal vein. The patient's condition is currently stable 17 months after diagnosis, with no tumor regrowth on account of repeated TACE and GEM therapy. The present case of unresectable combined hepatocellular-cholangiocellular carcinoma was successfully treated using TACE and systemic GEM chemotherapy.

Successful management of severe intrahepatic cholestasis of pregnancy: report of a first Japanese case.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a cholestasis condition caused by elevated levels of serum bile acids that mainly occurs in the third trimester of pregnancy. Maternal symptoms include pruritus; elevation of transaminases, biliary enzymes, and bilirubin levels; and abnormal liver function tests. Fetal symptoms include spontaneous preterm labor, fetal distress, and intrauterine death. It is more prevalent in the Caucasians and is rarely found in Asian countries, including Japan. The etiology of ICP has been reported as involving various factors such as, environmental factors, hormone balance, and genetic components. The genetic factors include single-nucleotide polymorphisms (SNPs) in the genes of canalicular transporters, including ABCB4 and ABCB11. It has also been reported that the combination of these SNPs induces severe cholestasis and liver dysfunction. CASE PRESENTATION: Here, we report for the first time a 24-year Japanese case of severe ICP diagnosed by typical symptoms, serum biochemical analysis, and treated with the administration of ursodeoxycholic acid which improved cholestasis and liver injury and prevented fetal death. The sequence analysis showed SNPs reported their association with ICP in the ABCB11 (rs2287622, V444A) and ABCB4 (rs1202283, N168N) loci. CONCLUSION: The risk of ICP has been reported to be population-specific, and it is rare in the Japanese population. Our case was successfully treated with ursodeoxycholic acid and the genetic sequence analysis has supported the diagnosis. Because genetic variation in ABCB4 and ABCB11 has also been reported in the Japanese population, we need to be aware of potential ICP cases in pregnant Japanese women although further studies are necessary.

Percutaneous transhepatic portal vein stent placement can improve prognosis for hepatocellular carcinoma patients with portal vein tumor thrombosis.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has an extremely poor prognosis. One reason is that portal hypertension may progress rapidly and intractable gastric/esophageal variceal hemorrhage may occur in PVTT cases. We studied whether a percutaneous transhepatic portal vein stent placement could improve the prognosis for HCC with PVTT. METHODOLOGY: Five cases of HCC with PVTT where portal hypertension had rapidly progressed were performed portal vein stenting. RESULTS: All cases had been classified into Child-Pugh class C. Only one of them died of liver failure five months after stent placement, but two of the cases successfully avoided dying of liver failure and the other two cases are still alive with a hepatic functional reserve maintained. CONCLUSIONS: Although portal vein stent placement for HCC with PVTT is not by itself a therapy for PVTT, portal vein stent placement plays a prominent role in improving hepatic function reserve preventing fatal hepatic failures due to PVTT and gastric/esophageal variceal hemorrhage associated with portal hypertension. This leads to prolonged survival for HCC patients with PVTT. Further prospective trials including the appropriate timing of portal vein stent placement treatment will be needed for larger numbers of HCC patients with PVTT.

Increase of fucosylated alpha-fetoprotein fraction at the onset of autoimmune hepatitis and acute liver failure.

AIM: Increased serum α-fetoprotein (AFP) has been associated with a good prognosis following acute liver failure (ALF), but the levels of the fucosylated fraction of AFP (Lens culinaris agglutinin-reactive fraction of AFP [AFP-L3]) following acute liver injury remain unknown. The aim of the present study was to investigate the clinical significance of AFP and AFP-L3 in patients with acute liver injury. METHODS: We investigated the serum levels of AFP and highly sensitive AFP-L3% in 27 patients with acute-onset autoimmune hepatitis (AIH), 28 patients with acute hepatitis (AH) and 22 patients with ALF at the onset using a highly sensitive immunoassay (micro-total analysis system). RESULTS: The serum AFP levels were increased in patients with AIH, AH and ALF, but the levels did not significantly differ among them. However, the mean AFP-L3% level was significantly higher in patients with AIH than in patients with AH (P = 0.0039). Moreover, significantly more patients with AIH demonstrated AFP-L3 positivity (≥10%) when compared with patients with AH (P = 0.014). Although the percentage of AFP-L3 positivity increased with AFP levels, at low serum AFP levels (<10 ng/mL), significantly more patients with AIH demonstrated AFP-L3 positivity than did patients with AH (P = 0.024) or ALF (P = 0.038). CONCLUSION: We demonstrated for the first time that highly sensitive AFP-L3% levels were increased at the onset of AIH. The mechanism underlying the increase in AFP-L3 remains to be elucidated, but this finding may reflect an alteration of the glycosylation such as hyperfucosylation, which can influence the modifications of self-antigens in hepatocytes.

Histopathology of the tissue adhering to the multiple tine expandable electrodes used for radiofrequency ablation of hepatocellular carcinoma predicts local recurrence.

OBJECTIVE: To assess the ability to predict the local recurrence of hepatocellular carcinoma by analyzing tissues adhering to the radiofrequency ablation probe after complete ablation. METHODS: From May 2002 to March 2011, tissue specimens adhering to the radiofrequency ablation probe from 284 radiofrequency ablation sessions performed for hepatocellular carcinomas ≤3 cm in size were analyzed. The specimens were classified as either viable tumor tissue or complete necrosis, and the local recurrence rates were calculated using the Kaplan-Meier method. RESULTS: From the tumors ≤3 cm in size, viable tissue was present in 6 (2.1%) of 284 specimens, and the local recurrence rates after 1 and 2 years of follow-up were 6.7% and 11.2%, respectively. Local recurrence developed significantly earlier in the viable tissue group. The recurrence rate was not significantly different based on whether transcatheter arterial chemoembolization was performed. CONCLUSION: The histopathology of the tissue adhering to the radiofrequency ablation probes used for hepatocellular carcinoma treatment can predict local recurrence. Additional aggressive treatment for patients with viable tissue can therefore improve the overall survival.

Efficacy of the regimen using twice-daily ß-interferon followed by the standard of care for chronic hepatitis C genotype 1b with high viral load.

AIM: In patients with refractory genotype 1b chronic hepatitis C with high viral loads, we retrospectively compared the efficacy of standard of care treatment (SOC: combined PEG-IFN-α-2b/ribavirin for 48 weeks) and a regimen in which 2 weeks of SOC induction was replaced by twice-daily ß-interferon alone (IFN-ß induction therapy). METHODS: Seventeen patients received the IFN-ß induction therapy plus SOC (IFN-ß induction group) and 13 patients received SOC alone (SOC group). RESULTS: In the IFN-ß induction group and SOC group, early virological response (EVR) rates were 88.2% and 53.8%, respectively. The end of treatment rates were 100.0% and 92.3%, and sustained virological response (SVR) rates were 70.6% and 53.8%, respectively. By induction with IFN-ß, even in refractory cases, the high virus negative conversion rate in the early treatment phase and actions of pegylated IFN-α-2b and ribavirin in the maintenance treatment phase led to an additive effect. In the analysis of contributing factors, only the achievement of EVR was associated with a significant difference in SVR (P = 0.0011). The univariate logistic regression analysis showed that only IFN-ß treatment was associated with a significant difference in EVR (P = 0.0492, odds ratio = 6.248, 95% confidence interval = 1.026-40.252), whereas no significant factors were found in the multivariate analysis due to small samples. CONCLUSION: IFN-ß induction therapy with higher EVR might be beneficial for protease inhibitor-refractory chronic hepatitis C patients.

Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C.

BACKGROUND/AIMS: To examine the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein-D (SP-D) as markers of interstitial pneumonitis. Many antiviral therapies have become available for chronic hepatitis C, including pegylated interferon (PEGIFN) plus ribavirin. Since interstitial pneumonitis is a serious adverse drug reaction during interferon therapy, interferon treatment requires caution in respiratory disease patients. Hence, the predictors of interstitial pneumonitis have not been elucidated. METHODOLOGY: Fifty-two chronic hepatitis C patients who received PEG-IFN plus ribavirin were studied; 14 patients received PEGIFN-α 2a, and 38 received PEG-IFN-α 2b. Serum KL-6 and SP-D levels were measured during treatment. Time changes in serum KL-6 and SP-D levels, as well as the presence of interstitial pneumonitis, were investigated. RESULTS: No cases of pneumonitis in which both markers were below the standard values were seen. Interstitial pneumonitis developed in 1 of the 5 patients in whom both markers were above standard values. Patients whose KL-6 levels alone exceeded the standard value had bacterial pneumonia and emphysema, not interstitial pneumonitis. Though no correlation between SP-D and KL-6 levels was observed, KL-6 levels tended to increase after interstitial pneumonitis was detected on imaging, but SP-D levels increased before imaging detection. CONCLUSIONS: It is important to monitor changes in levels of serum markers and other factors to avoid interstitial pneumonitis during PEG-IFN therapy. SP-D in particular may be important for early detection of interstitial pneumonitis.

Combination PEG-IFN a-2b/ribavirin therapy following treatment of hepatitis C virus-associated hepatocellular carcinoma is capable of improving hepatic functional reserve and survival.

BACKGROUND/AIMS: Hepatitis C virus (HCV) associated HCC shows a high rate of recurrence even after curative treatment. Outcomes of pegylated interferon PEGIFN a-2b/ribavirin (RBV) therapy for HCV-associated HCC have yet to be elucidated. We investigated therapeutic response and hepatic functional reserve improvement in patients receiving PEG-IFN a-2b/RBV after curative HCC treatment. METHODOLOGY: We investigated survival rate, metachronous recurrence and hepatic functional reserve in 54 patients with initial HCV-associated Stage I/II HCC; 29 patients were administered a preparation of PEG-IFN a-2b/RBV after HCC treatment (Secondary IFN group) and 25 were not (Non-secondary IFN group). RESULTS: A significant difference was observed in cumulative survival rates among HCV-associated HCC patients with rates of 100% after 1 year and 90.2% after 3 years in the secondary IFN group compared to 96.0% and 61.2%, respectively, in the non-secondary IFN group. Univariate analysis identified secondary IFN treatment, alanine aminotransferase and albumin levels as factors contributing to survival. Serum albumin level decreased temporarily but subsequently increased and improved hepatic functional reserve was observed in PEG-IFN a-2b/RBV therapy. CONCLUSIONS: PEG-IFN a-2b/RBV therapy after HCC treatment can improve hepatic functional reserve and may therefore represent a therapeutic option in the event of recurrence. PEG-IFN a-2b/ RBV therapy following HCC treatment shows promise for improving the prognosis of HCC.

Complete early virological response was highly achieved by double filtration plasmapheresis plus IFN-beta induction therapy for HCV-1b patients with relapse or no response after previous IFN therapy.

The efficacy of double filtration plasmapheresis (DFPP) plus interferon (IFN)-ß induction therapy was preliminarily investigated in re-treated patients with chronic genotype 1b hepatitis C and high viral load (patients with relapse or non-response to previous IFN therapies). In eight patients with chronic hepatitis C, DFPP was performed five times over 2 weeks during IFN-ß therapy, and 3 MU of IFN-ß was administered twice a day for 2 weeks. Combination therapies with ribavirin and pegylated IFN-α2b (PEG-IFN-α2b) or pegylated IFN-α2a (PEG-IFN-α2a) were subsequently used. After 4 weeks, hepatitis C virus (HCV)-RNA tended to be more greatly decreased with DFPP combination therapy than with previous IFN therapy (4.5 ± 2.0 log(10) IU/mL vs. 2.9 ± 1.2 log(10) IU/mL). Rates of both rapid virological response and complete early virological response were significantly higher with DFPP and IFN-ß induction therapy than with previous IFN therapy. DFPP plus IFN-ß induction therapy produced a great reduction of viral load during the early stage of treatment and achieved a high early virological response, suggesting that this combination therapy may be useful as a new treatment modality for chronic hepatitis C patients in difficult-to-treat states. This combination may contribute to sustained virological response (SVR). The effects of DFPP on SVR and its significance remain to be clarified.

Failure to achieve 2-log10 viral decrease in first four weeks of peg-IFNalpha-2b plus ribavirin therapy for chronic hepatitis C with genotype 1b and high viral titer is useful in predicting non-response: evaluation of response-guided therapy.

BACKGROUND/AIMS: To clarify clinical parameters predicting sustained viral response (SVR) during 48 weeks pegylated-interferon (peg-IFN)alpha-2b plus ribavirin therapy for Japanese patients with chronic hepatitis C [CH(C)] genotype 1b and high viral titers. METHODOLOGY: One hundred and fifty-one (151) patients receiving peg-IFNalpha-2b plus ribavirin therapy for 48 weeks were enrolled. SVR and clinical parameters were evaluated. The relationship between virological parameters (substitutions in the core and NS5A) and the degree of early viral decrease was also studied. RESULTS: Seventy (46.4%) patients achieved SVR (per protocol analysis). Negative predictive value (NPV) of <2-log10 decrease after 4 weeks of therapy for SVR was 78.0%; similar to that for failing to achieve early viral response (EVR) at 12 weeks (82.2%). CONCLUSIONS: Failure to achieve 2- log10 decrease in the first 4 weeks may be an important predictor of non-SVR during 48 weeks of peg-IFNalpha-2b plus ribavirin therapy; thus, therapeutic plans should be reassessed at that point.

Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma.

BACKGROUND: The effectiveness of additional chemotherapy in preventing intrahepatic distant tumor recurrence of hepatocellular carcinoma (HCC) has not been fully established. The authors compared the efficacy of 2 platinum-based chemotherapeutic agents in combination with radical local treatment for preventing intrahepatic distant recurrence (IDR). METHODS: Seventy-eight patients with stage I/II HCC aged 45 to 85 years underwent transcatheter arterial chemoembolization and/or radiofrequency ablation after they received hepatic arterial infusion (HAI) of platinum compounds. The HAI consisted of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) in 25 patients and cis-diamminedichloroplatinum (II) (cisplatin) in 53 patients. Multivariate analysis was used to identify independent factors that were associated with IDR. RESULTS: Cumulative IDR rates at 1 year, 2 years, and 3 years were 21.7%, 52.2% and 75.7%, respectively, in the carboplatin group and 8.1%, 22.7%, and 36.9%, respectively, in the cisplatin group. The cisplatin group had a significantly lower IDR rate compared with the carboplatin group. The selection of a platinum agent was 1 of the independent factors for IDR in a multivariate Cox proportional hazards model. CONCLUSIONS: HAI chemotherapy with cisplatin before radical local treatment was effective in patients with HCC. The authors concluded that radical local treatment with concurrent HAI using cisplatin may contribute to a longer progression-free period, which could be predicted with intrahepatic imaging in patients with stage I/II HCC.

Characterization of elevated alanine aminotransferase levels during pegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C.

AIM: Elevation of alanine aminotransferase (ALT) levels during pegylated-interferon (peg-IFN) plus ribavirin therapy in patients with chronic hepatitis C [CHC] is a problem that cannot be disregarded. The aim of this study is to assess the frequency and to characterize clinical parameters of this phenomenon. METHODS: Two hundred and thirty-five (235) CHC patients with genotype 1b receiving peg-IFN α-2b plus ribavirin therapy were analyzed. Clinical parameters that may be associated with abnormal ALT values during treatment and therapy outcomes were evaluated statistically. One hundred and sixteen (116) patients treated with peg-IFN α-2a plus ribavirin were also included for partial analysis. RESULTS: Abnormal ALT values during treatment were observed in 23.0% of patients. It was observed in 14.5% of those with sustained virological response (SVR) and 17.8% of those with relapse, in whom viral clearance was observed during therapy. Multivariate logistic regression analysis revealed that pretreatment ALT values, therapy outcome, and body mass index (BMI) were significant factors related to abnormal ALT values during treatment. Abnormal ALT values during treatment became normal in SVR patients at 6 months after the completion of treatment, but not in NR (non-response) patients. Mean ALT values were significantly higher at some time points during treatment in patients treated with α-2a when compared to those treated with α-2b. CONCLUSION: Abnormal ALT values during peg-IFN plus ribavirin treatment are observed relatively frequently, even in patients without detectable HCV RNA. Direct or indirect involvement of drugs is considered as one possible cause.

Gemcitabine in arterial injection chemotherapy for pancreatic cancer does not cause catheter obstruction or any other complication.

BACKGROUND/AIMS: Intra-arterial injection therapy is performed to ensure more localized administration; however, this approach has led to more cases of catheter obstruction during the course of treatment for pancreatic cancer than in any other type of cancer. Therefore, the purpose of this study was to verify the resistance of catheters to gemcitabine. METHODOLOGY: The catheters were prepared by injecting gemcitabine into the lumen, which was subsequently closed by clipping both ends. After incubation, the gemcitabine in the lumen of the catheter was removed, the breaking strength was measured by pulling 1 side of the catheter at a speed of 500 mm/min to test the tensile strength. To verify the surface of the lumen, the lumen was observed with an electron microscope. RESULTS: Soaking the lumen revealed no significant differences in breaking strength due to abusive treatment conditions. Electron microscopy revealed residual microscopic amounts of gemcitabine in the lumen but with no marked deterioration or alteration in the quality of the tube surface. CONCLUSIONS: Gemcitabine had no chemical effect on the intra-arterial injection catheter. It is possible that a thrombotic tendency in pancreatic cancer patients may be responsible for the high frequency of catheter occlusion in patients with this disease.

Usefulness of Y-shaped sheaths in CT angiography for examination of liver tumors.

AIM: To conduct a single-stage, combined computed tomography (CT) arterial portography (CTAP) and CT arteriography (CTA) imaging operation, we used Y-shaped sheaths with 2 valves, which allowed the insertion of 2 catheters simultaneously. METHODS: Of 1254 patients who underwent abdominal angiography for transarterial embolization and/or intraarterial chemotherapy in our department from May 2002 to November 2009, 664 patients in whom Y-shaped sheaths with 2 valves were used underwent CT angiography using a combination of CTA and CTAP. The Seldinger method was used to insert a 10 cm Y-shaped short sheath with 2 valves into the femoral artery. Under radiographic guidance, a 3.2 French (Fr) catheter was placed in the celiac artery or proper hepatic artery, and a second 3.2 Fr catheter was then placed distal to the inferior pancreaticoduodenal artery of the superior mesenteric artery. CTAP was then performed followed by CTA 10 min later. Photographs were taken during the early and late phases of the procedure. RESULTS: Insertion of 3.2 Fr catheters was not possible in 6 of 664 (0.9%) patients with strong curvature of the femoral artery and 4 of 664 (0.6%) patients with strong curvature of the abdominal aorta. In addition, performing CTAP and CTA as a single-stage combined intervention was not possible in 14 of 664 (2.1%) patients whose right hepatic artery originated from the superior mesenteric artery and in 8 of 664 (1.2%) patients whose left hepatic artery branched from the left gastric artery. There were no sheath-related complications such as those related to arterial dissection or hemostasis. CONCLUSION: Although transfers to and from the CT room were necessary for anatomically variant patients, CT angiography using the Y-shaped sheath for combined CTAP and CTA was considered useful.

[Multiple liver metastases due to sigmoid colon cancer successfully treated by degradable starch microspheres (DSM)-TAE, radiofrequency ablation therapy, and Uzel/UFT].

A69-year-old man was diagnosed with sigmoid colon cancer and underwent resection of the sigmoid colon. He was later diagnosed with multiple liver metastases 11 months after resection of the sigmoid colon cancer. He was treated by intraarterial chemoembolization using degradable starch microspheres (DSM) and radiofrequency ablation therapy. As a systemic therapy, combined oral administration of tegafur/uracil (UFT) and Leucovorin(Uzel) was started (UFT 450 mg/day, Leucovorin 75 mg/day, 4 weeks of therapy followed by a 1-week treatment break). Two months after 4 courses, the liver metastases had markedly diminished and CEA was within the normal range. The metastases had almost disappeared and tumor markers decreased to within normal limits. This treatment was very safe and effective. Such a strategic multidisciplinary treatment can lead to a better prognosis for colorectal cancer with liver metastases.

Oral branched-chain amino acids administration improves impaired liver dysfunction after radiofrequency ablation therapy for hepatocellular carcinoma.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is a new modality for hepatocellular carcinoma (HCC). However, the effects of RFA on hepatic reserve have not yet been thoroughly studied. In the present study, it was evaluated the effect of branched chain amino acid (BCAA) administration after RFA. METHODOLOGY: Fifty-seven patients with initial, single HCC lesions measuring not more than 30mm in whom RFA was selected in first-line therapy were enrolled. Twenty-eight patients with the Child-Pugh B/C grade who received RFA therapy were divided into two groups: 11 who received a BCAA-enriched nutrient mixture, and 17 who did not. Changes in serum albumin were evaluated before RFA and 1, 6 and 12 months after RFA. RESULTS: Multivariate analysis showed that the Child-Pugh grading is the most important factor related to intrahepatic distant recurrence following by RFA. Serum albumin levels decreased 1 month after RFA. Although a tendency toward recovery was noted 6 months after RFA, a decreasing tendency was noted again one year after RFA compared to the pre-RFA baseline. However, a tendency toward improvement was noted in Child-Pugh B grade patients who received BCAA mixture. CONCLUSIONS: BCAA mixture made it possible to maintain serum albumin levels and hepatic reserve.

Therapeutic efficacy of continuous arterial infusion of the protease inhibitor and the antibiotics and via celiac and superior mesenteric artery for severe acute pancreatitis--pilot study.

BACKGROUND/AIMS: Severe acute pancreatitis is poor prognosis. Continuous regional arterial infusion of protease inhibitors and antibiotics were developed in Japan. We evaluated whether arterial infusion both celiac artery and superior mesenteric artery for this disease would reduce mortality. METHODOLOGY: Seventeen patients were treated arterial infusion of protease inhibitor and antibiotics via both celiac artery and superior mesenteric artery. Changes of Acute Physiology and Chronic Health Evaluation II score and mortality were evaluated. RESULTS: Arterial infusion via two routes reduced the mortality rate and improved Acute Physiology and Chronic Health Evaluation II score. The overall mortality rate was 11.8%. The mortality rate in patients in whom were treated within 3days after the onset was significantly lower than that in patients in whom were treated without 3days after the onset. CONCLUSIONS: Arterial infusion via superior mesenteric artery might prevent both bacterial translocation and non-occlusive mesenteric ischemia. Continuous arterial infusion both celiac artery and superior mesenteric artery might be effective for reducing mortality and preventing the development of pancreatitis, especially when initiated within 3 days after the onset. Further prospective randomized studies using a larger number of patients are required.

Successful treatment of multiple lung metastases of hepatocellular carcinoma by combined chemotherapy with docetaxel, cisplatin and tegafur/uracil.

We report the successful treatment of multiple lung metastases after hepatic resection for hepatocellular carcinoma (HCC) with combined docetaxel, cisplatin (CDDP), and enteric-coated tegafur/uracil (UFT-E). A 68-year-old man was diagnosed with multiple lung metastases of HCC 7 mo after partial hepatectomy for HCC. Oral UFT-E was given daily and docetaxel and CDDP were given intra-arterially (administered just before the bronchial arteries) every 2 wk via a subcutaneous injection port. One month after starting chemotherapy, levels of tumor marker, protein induced by vitamin K absence II (PIVKA-II), decreased rapidly, and after a further month, chest X-ray and computed tomography revealed the complete disappearance of multiple liver metastases. Two years after the combined chemotherapy, HCC recurred in the liver and was treated but no pulmonary recurrence occurred. In the absence of a standardized highly effective therapy, this combined chemotherapy with docetaxel, CDDP and UFT-E may be an attractive option for multiple lung metastases of HCC.

Successful treatment with lamivudine may correlate with reduction of serum ferritin levels in the patients with chronic hepatitis and liver cirrhosis type B.

PURPOSE: To study the changes in serum ferritin levels in lamivudine (LAM)-treated patients with chronic hepatitis and liver cirrhosis type B and determine whether successful treatment with LAM results in a reduction of serum ferritin levels. METHODS: Thirty patients with chronic hepatitis B virus (HBV) infection were followed prospectively during their treatment with LAM for 12 months. Serum HBV DNA, ferritin levels, and emergence of YMDD mutants were monitored. A case of severe liver cirrhosis with hepatic hemosiderosis that was treated successfully with LAM also is shown as a representative case. RESULTS: Serum alanine aminotransferase and ferritin levels decreased significantly more in the patients treated with LAM without YMDD mutants (n = 23) than those with mutants (n = 7). Hepatic hemosiderosis along with serum iron markers improved greatly in the representative patient. CONCLUSION: Successful treatment with LAM may reduce serum ferritin levels and improve hepatic siderosis in a subset of patients with chronic HBV infection.

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: a pilot study.

AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil. RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) mo. One patient showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the two patients showed partial response (PR), response rate (CR + PR/All cases 30%). The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable. CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.