Prediction of a sustained viral response in chronic hepatitis C patients who undergo induction therapy with double filtration plasmapheresis plus interferon-ß/ribavirin.

The aim of the present study was to determine predictors of a sustained virological response (SVR) with a regimen of double filtration plasmapheresis (DFPP) combined with interferon-ß plus ribavirin (IFN-ß/RBV) induction therapy prior to pegylated (PEG-IFN/RBV) standard of care (SOC) therapy for patients with chronic hepatitis C who had experienced SOC treatment failure. Predictors of a SVR were analyzed in chronic hepatitis C patients with genotype 1b hepatitis C virus (HCV), who had a high viral load. The patients had been unresponsive to previous IFN therapy and underwent induction therapy with IFN-ß/RBV plus DFPP, which was performed five times during the same period, followed by PEG-IFN/RBV. In total, 10 patients received the combination DFPP plus IFN-ß/RBV induction therapy prior to PEG-IFN/RBV therapy for the treatment of chronic hepatitis C. Two weeks after treatment initiation, a decrease in the HCV RNA levels of ≥2 log IU/ml occurred in 9/10 patients (90%), while a decrease of ≥4 log IU/ml was observed in 4/10 patients (40%). The HCV RNA levels at week 2 after treatment initiation in the SVR and non-SVR patients decreased by 5.0±0.8 and 2.9±1.1 log IU/ml, respectively. Despite no response to previous IFN therapy, three of the 10 patients (30%) experienced a SVR. The results indicated that a rapid virological response ensued following IFN-ß/RBV induction and DFPP supplementary therapy. Although the level of interleukin-28B is an important predictor of a SVR, a decrease in the HCV RNA volume of ≥4 log IU/ml at week 2 after the initial treatment is also an important predictor. Therefore, rapid virological reduction using DFPP, in addition to IFN-ß/RBV induction therapy, is an important predictor of a SVR.

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.

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.

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.

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.

CT-maximum intensity projection is a clinically useful modality for the detection of gastric varices.

AIM: To evaluate the efficacy of CT-maximum intensity projection (CT-MIP) in the detection of gastric varices and their inflowing and outflowing vessels in patients with gastric varices scheduled to undergo balloon-occluded retrograde transvenous obliteration (B-RTO). METHODS: Sixteen patients with endoscopically confirmed gastric varices were included in this study. All patients were evaluated with CT-MIP using three-dimensional reconstructions, before and after B-RTO. RESULTS: CT-MIP clearly depicted gastric varices in 16 patients (100%), the left gastric vein in 6 (32.5%), the posterior gastric vein in 12 (75.0%), the short gastric veins in 13 (81.3%), gastrorenal shunts in 16 (100%), the hemiazygos vein (HAZV) in 4 (25.0%), the pericardiophrenic vein (PCPV) in 9 (56.3%), and the left inferior phrenic vein in 9 patients (56.3%). Although flow direction itself cannot be determined from CT-MIP, this modality provided clear images of the inflowing and the outflowing vessels. Moreover, in one patient, short gastric veins were not seen on conventional angiographic portography images of the spleen, but were clearly revealed on CT-MIP. CONCLUSION: We suggest that CT-MIP should be considered as a routine method for detecting and diagnosing collateral veins in patients with gastric varices scheduled for B-RTO. Furthermore, CT-MIP is more useful than endoscopy in verifying the early therapeutic effects of B-RTO.