[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.

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.

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.

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.

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.

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.

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.

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.

[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.

Angiotensin-II administration is useful for the detection of liver metastasis from pancreatic cancer during pharmacoangiographic computed tomography.

AIM: To improve the preoperative diagnosis of liver metastasis from pancreatic cancer, we estimated computed tomography during arterial angiography (CTA) with/without administration of angiotensin-II (AT- II). METHODS: Thirty-five patients with pancreatic cancer were examined in this study. After conventional CTA was performed, pharmacoangiographic CTA was performed with a 1-3 microgram/5 mL solution of angiotensin II injected through a catheter into the celiac artery during spiral computed tomography. We prospectively analyzed the relative region of interest (ROI) ratio of tumor to liver with/without AT-II. RESULTS: In all patients, the relative ratio of each computed tomography (CT) number in the ROI was larger at pharmacoangiographic CT than at conventional angiographic CT. Administration of angiotensin-II enhanced the metastatic liver tumor as compared with normal tissue. Intratumoral blood flow increased in all patients with malignant tumors due to the pressure effect of AT-II. Furthermore, the metastatic lesions in the liver of three patients were represented by only pharmacoangiographic CT, not by conventional CT and conventional CT angiography. In even peripheral and central areas of metastatic liver tumor, the lesions were enhanced after administration of AT-II. CONCLUSION: These results support that high detection rate of liver metastasis revealed by pharmacoangiographic CT suggests the improvement of diagnosis on preoperative staging. Moreover, chemotherapy under AT-II induced hypertension may have a better effect on the treatment of metastatic liver tumors.

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.

Clinical efficacy of intra-arterial pharmacokinetic chemotherapy with 5-fluorouracil, CDDP, gemcitabine, and angiotensin-II in patients with advanced pancreatic cancer.

BACKGROUND/AIMS: To deliver anticancer drugs more selectively into cancer tissues and to improve survival time, we have developed a new method of intra-arterial chemotherapy for unresectable pancreatic cancer. METHODOLOGY: From April 2002 to June 2006, twenty patients with pancreatic cancer with liver metastases were given intra-arterial infusions consisting of gemcitabine, 5-FU, and cisplatin mixed with angiotensin-II with the intent of increasing the blood flow into the tumor tissue but decreasing that to the non-tumor tissues. Simultaneously, tegafur/uracil was administered. A tumor marker and computed tomography (CT) findings were used to evaluate the efficacy of this chemotherapy. RESULTS: The median survival was 365 days, and 6-months and 1-year survival rates were 80.0% and 44.7%, respectively. In 12 of 20 cases, the tumor marker level was decreased after this chemotherapy. In 10 of 20 cases, computed tomography showed a decrease in the tumor size. In 6 patients, back pain was the chief complaint and was reduced to a self-controlled level in 20 patients. No major complications were encountered. CONCLUSIONS: Compared with the previously reported data in traditional chemotherapies, our method of intra-arterial chemotherapy appears to be quite useful not only for prolonging patient survival but also for improving the quality of life. Intra-arterial regional chemotherapy including changes in distribution of blood flow induced by angiotensin-II appears to be an effective palliative treatment for advanced pancreatic cancer.

[A resected case of fibrolamellar hepatocellular carcinoma with chronic hepatitis (type B)].

We report a case of a 34-year-old woman who tested positive for HBs Ag with fibrolamellar hepatocellular carcinoma of the liver. The sister of this patient, who was also positive for HBs Ag, died of hepatocellular carcinoma (HCC). The patient showed elevation of alpha-fetoprotein. Abdominal CT scan showed a tumor in the posterior segment of the liver and hepatic angiography revealed marked neovascularity in the tumor. Partial resection of the liver was performed, and the histological diagnosis was fibrolamellar hepatocellular carcinoma. The patient is now tumor free and doing well 20 months after the operation.

[A case of splenic inflammatory pseudotumor].

A 59-year-old man was admitted to our hospital because of continuous C-reactive protein elevation. Abdominal computed tomography scan revealed a low density mass on the surface of the spleen. Magnetic resonance imaging showed low intensity at peripheral area and slightly high intensity in the central area of the mass lesion on T1 and T2-weighted image. Splenectomy was performed since we could not rule out the possibility of malignant neoplasm only by diagnostic imaging. The pathological diagnosis of the tumor was inflammatory pseudotumor. Splenectomy is considered to be significant from the standpoints of both diagnosis and therapy in cases in which diagnostic imaging is difficult to interpret.

Comparison of a new aspiration needle device and the Quick-Core biopsy needle for transjugular liver biopsy.

AIM: To evaluate sample adequacy, safety, and needle passes of a new biopsy needle device compared to the Quick-Core biopsy needle for transjugular liver biopsy in patients affected by liver disease. METHODS: Thirty consecutive liver-disease patients who had major coagulation abnormalities and/or relevant ascites underwent transjugular liver biopsy using either a new needle device (18 patients) or the Quick-Core biopsy needle (12 patients). The length of the specimens was measured before fixation. A pathologist reviewed the histological slides for sample adequacy and pathologic diagnoses. The two methods'specimen adequacy and complication rates were assessed. RESULTS: Liver biopsies were technically successful in all 30 (100%) patients, with diagnostic histological core specimens obtained in 30 of 30 (100%) patients, for an overall success rate of 100%. With the new device, 18 specimens were obtained, with an average of 1.1 passes per patient. Using the Quick-Core biopsy needle, 12 specimens were obtained, with an average of 1.8 passes per patient. Specimen length was significantly longer with the new needle device than with the Quick-Core biopsy needle (P < 0.05). The biopsy tissue was not fragmented in any of the specimens with the new aspiration needle device, but tissue was fragmented in 3 of 12 (25.0%) specimens obtained using the Quick-Core biopsy needle. Complications included cardiac arrhythmia in 3 (10.0%) patients, and transient abdominal pain in 4 (13.3%) patients. There were no cases of subcapsular hematoma, hemoperitoneum, or sepsis, and there was no death secondary to the procedure. In particular, no early or delayed major procedure-related complications were observed in any patient. CONCLUSION: Transjugular liver biopsy is a safe and effective procedure, and there was significant difference in the adequacy of the specimens obtained using the new needle device compared to the Quick-Core biopsy needle. Using the new biopsy needle device, the specimens showed no tissue fragmentation and no increment in major procedure-related complications was observed.

Absence of pretreatment markers that predict the emergence of YMDD mutants during lamivudine treatment--the results of a prospective multi-center study.

BACKGROUND/AIMS: The emergence of YMDD mutants in patients who are treated with lamivudine may determine the clinical prognosis. However, currently there are no clinical or virological factors that predict specifically the emergence of the mutants. METHODOLOGY: To define these factors, we analyzed 69 patients with chronic hepatitis B infection who were treated with lamivudine (LAM) and followed prospectively for at least 12 months. RESULTS: Of the 69 patients, 12 (17.4%) developed YMDD mutants up to 12 months after the start of LAM. The incidence of YMDD mutants was slightly higher in those who were younger, had higher HBV DNA titers, lower ALT levels, genotype C, and mutations in the core promoter before treatment. However, we could not find any significant factors that correlated with the appearance of the mutants. CONCLUSIONS: Currently, using conventional virological assays, it is difficult to predict the development of mutants before LAM treatment. Management of flare-ups of hepatitis, due to the appearance of mutants, should always be envisaged when LAM treatment is started.

[Gemcitabine versus combined chemotherapy with 5-fluorouracil and cisplatin in advanced pancreatic cancer].

Gemcitabine hydrochloride (GEM) is a first-line therapeutic agent for advanced pancreatic cancer, but there is no established second-line treatment after GEM failure. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 19 patients compared with GEM in 32 patients, respectively. Tumor response rates were 10.5% and 15.6% for FP therapy and GEM, respectively. The median survival time in the FP therapy and GEM was 137 days and 241 days, respectively. Although clinical benefit was similar in both types of therapy, median survival time was more favorable for GEM, especially for Stage IVb. Nausea and vomiting were the most commonly observed toxicity in the FP therapy group. Our data indicate that FP therapy is not considered to be a useful second-line agent in patients with GEM pretreated pancreatic cancer.