A case of generalized pustular psoriasis caused by hydroxychloroquine in a patient with systemic lupus erythematosus.

Hydroxychloroquine (HCQ) has been used to treat systemic lupus erythematosus (SLE) in Japan since 2015. We herein report a case of SLE that developed generalized pustular psoriasis (GPP) following the administration of HCQ. Twenty-one days after the HCQ treatment, a pustular rash with itching appeared on the auricle, scalp, and forearm, and spread rapidly to the face and body trunk with a high fever and arthralgia. Skin biopsy showed pustule formation under the cornified layer, neutrophil infiltration, the destruction of keratinocytes, and spongiform pustules of Kogoj. The patient was diagnosed with GPP. HCQ was immediately discontinued, the dose of prednisolone (PSL) was increased, and granulocyte and monocyte adsorption apheresis was performed. Her symptoms subsequently disappeared. Since arthralgia relapsed after the tapering of PSL, cyclosporine was added. Although single nucleotide polymorphisms (c.28C>T and c.115+6T>C) in the interleukin (IL)-36RN gene, which encodes the IL-36 receptor antagonist, have frequently been reported in GPP, these mutations were not observed in the present case. The potential development of GPP needs to be considered when administering HCQ to patients with SLE.

[Postoperative chemotherapy with a novel oral anticancer drug composed of tegafur, gimeracil and oteracil potassium to curability C scirrhus type gastric cancer].

We report the a case of 60-year-old male whose final finding was curability C and stage IV scirrhus type gastric cancer because of N3, CY1 and DM (+) treated with a novel oral anticancer drug composed of tegafur (FT), Gimeracil (CDHP) and Oteracil Potassium (Oxo) in a molar ratio of 1:04:1 after operation. This drug was administered orally twice daily after meals at a dose of 80 mg/body/day. One cycle consisted of consecutive administration for 28 days and 14 days rest, and this treatment cycle was repeated twice. Postoperative abdominal CT showed swollen paraaortic lymph nodes regarded as metastasis. However, they were reduced after 1 cycle and remained so. The serum carcinoembryonic antigen (CEA) level had decreased after 1 cycle. The patient's performance status (PS) had also recovered without severe side effects. It was considered that this anticancer drug composed of FT, CDHP and Oxo was effective to scirrhus type gastric cancer and useful as an adjuvant chemotherapy in view of the patient's living quality.

Effect of sodium thiosulfate on cisplatin removal with complete hepatic venous isolation and extracorporeal charcoal hemoperfusion: a pharmacokinetic evaluation.

BACKGROUND: Complete hepatic venous isolation and extracorporeal charcoal hemoperfusion (HVI.CHP) can limit systemic exposure to high-dose chemotherapeutic agents when given by hepatic arterial infusion (HAI). The purpose of this study was to determine if the concomitant use of sodium thiosulfate (STS) could further expand the advantages of pharmacologic delivery of HVI.CHP for cisplatin (CDDP) during HAI chemotherapy. METHODS: CDDP (4mg/kg) was administered over 20 minutes via HAI under conditions of HVI.CHP in 14 mongrel dogs. HVI.CHP was performed for 30 minutes after initiation of HAI. During CDDP infusion, 7 dogs each received 400 mg/kg STS (a 100-fold molar ratio to CDDP) over 20 minutes via the prefilter (STS group) circuit line, while the remaining 7 dogs (controls) received no STS. Blood samples were taken serially from the prefilter circuit line (hepatic venous blood), postfilter line, and the left carotid artery (systemic blood). The free and total CDDP concentrations in these samples were determined by flameless atomic absorption spectrophotometry. RESULTS: During 20 minutes HAI of CDDP, the mean CDDP extraction ratios (ER) by CHP filter were always higher in the STS group than in the control group, regardless of the form (free or total) of CDDP. The differences between the STS and control groups in the extraction ratios of free and total CDDP were significant at all time points measured (P < .05). Consequently, systemic exposure to CDDP, as assessed by area under the time-concentration curve of total CDDP, was significantly lower in the STS group than in the control group (P < .05). CONCLUSIONS: These results indicated that concomitant STS infusion could further increase the effect of HVI.CHP on CDDP removal after HAI.

Successful rescue of severe recurrent hepatitis C with interferon and ribavirin in a liver transplant patient.

BACKGROUND: Rapid graft dysfunction caused by hepatitis C virus (HCV) reinfection, although uncommon, is a disastrous complication in liver transplant patients. Finding an effective therapy for this subgroup of patients with severe recurrent HCV is a priority. METHOD: We describe a successful rescue of a 46-year-old man with recurrent hepatitis C (HCV genotype 1b) using long-term interferon (IFN) and ribavirin. The patient had a very aggressive type of posttransplantation HCV infection, as judged by biochemical and histologic findings. RESULTS: Despite high pretreatment values of serum alanine aminotransferase (ALT; peak value of 901 IU/L) and HCV-RNA (2.3 x 10(6) copies/ml), the combination therapy with IFN and ribavirin produced a rapid normalization of the serum ALT values, accompanied by the clearance of serum HCV-RNA. Although HCV-RNA reappeared in the serum at 3 months, the patient had continued ALT normalization and histological improvement with follow-up of over 26 months to date after the initiation of the combination therapy. CONCLUSION: This observation suggests that IFN in combination with ribavirin may offer an effective therapeutic option for liver transplant patients with severe recurrent hepatitis C.

Stimulation of haematogenous liver metastases by ischaemia-reperfusion in rats.

OBJECTIVE: To find out whether hepatic ischaemia-reperfusion stimulates hepatic tumour metastases using a cell line of rat ascitic hepatoma (AH130). DESIGN: Prospective experimental study. SETTING: University laboratories, Japan. MATERIALS: 118 male Donryu rats. INTERVENTION: After laparotomy alone (group 1, n = 35) or laparotomy and 20-minutes ischaemia (group 2, n = 34) or laparotomy and 30-minutes ischaemia (group 3, n = 34) of the median and left hepatic lobes, the animals were given either an intraportal injection of 1 x 10(5) or an intravenous injection of 1 x 10(6) viable AH130 cells. MAIN OUTCOME MEASURES: 10 days after inoculation of tumour cells the number of nodules on the surface of the right lobe and of the median plus left lobes were separately counted for each liver. RESULTS: Irrespective of the route of tumour inoculation in group 1, there was no significant difference in the number of tumours/g liver between the right and the median plus left lobes. However, in groups 2 and 3, the number of tumours/g liver in the median plus left lobes was significantly higher than in the right lobe (p < 0.05). Furthermore, in the median plus left lobes, animals who had had 30 minutes of ischaemia had significantly more tumours than those in the other two groups (p < 0.01). CONCLUSION: Hepatic ischaemia-reperfusion may increase the risk of development of haematogenous liver metastases, by stimulating tumour cell-endothelial cell interactions.

[The long-term results of percutaneous isolated hepatic perfusion for patients with advanced hepatocellular carcinoma].

We studied the long-term outcome of percutaneous isolated hepatic perfusion (PIHP) for patients with hepatocellular carcinoma. This study included 31 patients with Stage IVA and 5 with IVB disease treated by PIHP until December, 1997. The mean age and tumor diameter were 55 and 7.7 cm, respectively. Twenty-two had portal vein invasion, 13 had hepatic vein invasion, and all patients had multiple intrahepatic metastases of more than 5 tumor foci. The PIHP with adriamycin or cisplatin was undertaken in a total of 50 treatments in these 36 patients. CR was observed in 6 and PR in 13 with an overall response rate of 59%, excluding 4 patients who were not evaluable. Five of 6 patients with CR remain free of disease at 7 to 54 months after the first treatment. The overall survival rate was 67% at 1 year and 32% at 5 years. The survival rates of Stage IVA patients (1-year = 71%, 5-year = 36%) were higher than Stage IVB patients (1-year = 20%, 5-year = 0%). The 5-year survival rates of patients with vascular invasion (Vp1-3 = 23%, Vv1-3 = 8%) were lower than those without it (Vp0 = 47%, Vv0 = 51%). These results indicated that PIHP achieved a 5-year survival rate of approximately 40% in patients with multiple advanced hepatocellular carcinoma in the absence of distant organ metastases and marked vascular invasion, and yielded complete long-term remission in some of these patients.

[Experimental study on TNF-alpha linked percutaneous isolated hepatic chemoperfusion (PIHP)].

Recently, isolated hepatic perfusion (IHP) with high-dose TNF-alpha for hepatic malignancies has again attracted attention as a locoregional chemotherapy. A novel system of hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) is a minimal invasive surgery for high-dose chemotherapy of the liver. This study was undertaken to determine whether this novel system could limit systemic exposure to TNF-alpha following hepatic arterial infusion (HAI) when combined with anti TNF-alpha antibody. Beagles were allocated into two groups; group I (n = 4), TNF-alpha + anti TNF-alpha antibody and group II (n = 5), TNF-alpha only (control). All animals received HAI of 50 micrograms/kg of recombinant human TNF-alpha over 20 min with complete hepatic venous isolation. In group I, 250 micrograms/kg of antibody was administered into the hepatic venous outflow line over 30 min after the initiation of HAI. The Cmax (ng/ml) of systemic TNF level was significantly lower in group I (125 +/- 57) than in group II (825 +/- 283) (p < 0.05). The AUC (mg.min/ml) of the systemic TNF level was significantly lower in group I (2.0 +/- 1.0) than in group II (34.5 +/- 9.5) (p < 0.01). By use of anti TNF antibody, systemic exposure to TNF was reduced efficiently. These results indicated that HVI.CHP may be applicable to the TNF-alpha linked chemoperfusion to the liver in combination with anti TNF-alpha antibody.

Regional pharmacokinetics of doxorubicin following hepatic arterial and portal venous administration: evaluation with hepatic venous isolation and charcoal hemoperfusion.

We evaluated the regional pharmacokinetics of doxorubicin after hepatic arterial infusion (HAI) and portal venous infusion (PVI) using a novel system for hepatic venous isolation and charcoal hemoperfusion (HVI-CHP). The HVI-CHP system was used to determine directly the doxorubicin plasma concentration in the hepatic vein and the hepatic venous flow rate, and simultaneously, to eliminate hepatic re-entry of the drug. Beagles received doxorubicin (1 mg/kg) through either the hepatic artery (HAI group, n = 6) or the portal vein (PVI group, n = 6). In both groups, hepatic venous blood was completely isolated and directed to the CHP filter. The filtered blood was returned through the left jugular vein. During HVI-CHP, the hepatic venous flow rate was monitored and plasma doxorubicin concentrations were serially measured in prefilter (= hepatic venous), postfilter, and systemic blood. The hepatic tissue uptake of doxorubicin was determined based on the blood flow rate and doxorubicin level in the hepatic vein. The hepatic extraction ratio of doxorubicin was defined as the percentage hepatic tissue uptake to the amount of drug administered. During drug infusion, similarly in either group, HVI-CHP produced a 66-87% reduction of the postfilter doxorubicin level as compared with the prefilter level. The prefilter drug level was significantly lower in HAI group than in PVI group (P < 0.01). Thus, the area under the time concentration curve for the prefilter drug level in the HAI group (6.90+/-0.96 microg min/ml) was significantly lower than that in the PVI group (18.10+/-2.90 microg min/ml, P < 0.01). Conversely, the hepatic extraction ratio in the HAI group (84.6+/-2.9%) was significantly higher than that in the PVI group (58.1+/-3.4%, P < 0.01). We conclude that in the beagle, doxorubicin is more effectively extracted by the liver when administered via the hepatic artery than when administered via the portal vein. These results indicate that HAI of doxorubicin is superior to PVI in terms of reduction of systemic drug exposure and systemic toxicity.

Percutaneous isolated liver chemoperfusion for treatment of unresectable malignant liver tumors: technique, pharmacokinetics, clinical results.

We have developed a single-catheter technique for percutaneous isolated liver chemoperfusion (PILP) with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) for the treatment of malignant liver tumors. We report here the surgical technique, pharmacokinetics, and effectiveness of PILP in multiple advanced liver tumors. Twenty-eight patients with hepatocellular carcinoma (HCC) and 18 with metastatic liver tumors underwent a total of 61 PILPs with HVI-CHP. HVI-CHP was accomplished mainly by the single-catheter technique using a novel four-lumen, two-balloon catheter; it was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. Under HVI-CHP, either doxorubicin 960-150 mg/m2) or cisplatin (150-200 mg/m2) was infused via the hepatic artery. The PILP was completed successfully in all 61 trials. Two of forty-six patients died early; one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Excluding these two deaths, the treatments were well tolerated. The major side effects were mild to moderate chemical hepatitis and reversible myelosuppression. Of the 27 evaluable HCC patients, 17 (63%) had an objective tumor response (5 complete and 12 partial responses). In 15 patients with colorectal hepatic metastases (CHM), 7 had a sharp decrease in serum carcinoembryonic antigen (CEA) levels (to < 50% of their pretreatment levels) after treatment. However, a single PILP had limited efficacy in terms of the durability of remission (< or = 6 months in most CHM patients, as assessed by CEA levels). These results indicate that PILP with HVI-CHP has high efficacy in most patients with multiple advanced liver tumors. In addition, the results suggest a role of multiple treatment courses of PILP in the induction of long-term remission, especially for patients responsive to the first treatment.

Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion.

OBJECTIVE: The aim of this study was to report the long-term results of percutaneous isolated liver chemoperfusion with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The results of conventional chemotherapy including regional and systemic chemotherapy in patients with HCC remain dismal, and long-term survivors after treatment are rare among patients with multiple advanced HCC. In an effort to improve this situation, we previously developed a novel system of percutaneous isolated liver chemoperfusion with HVI-CHP. METHODS: Doxorubicin (60 to 150 mg/m2) was administered via the hepatic artery, under conditions of extracorporeal drug elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished mainly by the single catheter technique using a newly developed 4-lumen-balloon catheter, which was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. RESULTS: Complete remission was achieved in five patients, of which four received repeated treatments (two or three times). Although 1 of 5 patients with complete remission died of pulmonary metastases at 8 months, the other 4 remain healthy and free of disease at 20, 24, 27, and 42 months after the first treatment. Partial responses were observed in 12 patients. Duration of response in responders (complete and partial) with repeated treatments was significantly longer than that with a single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method was 39.7% at 5 years. The treatments were well-tolerated, and the primary side effects were mild to moderate chemical hepatitis and reversible myelosuppression. CONCLUSIONS: The results suggest that percutaneous isolated liver chemoperfusion with HVI-CHP is an effective palliative treatment in the majority of patients and yields long-term complete remission in some patients with multiple advanced HCC.

Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein.

The inhibitory effects of SDZ PSC 833 (PSC833), a non-immunosuppressive cyclosporin derivative, on the P-glycoprotein (P-gp)-mediated transport of doxorubicin and vinblastine were compared with those of cyclosporin A (Cs-A). The transcellular transport of the anticancer drugs and PSC833 across a monolayer of LLC-GA5-COL150 cells, which overexpress human P-gp, was measured. Both PSC833 and Cs-A inhibited P-gp-mediated transport of doxorubicin and vinblastine in a concentration-dependent manner and increased the intracellular accumulation of doxorubicin and vinblastine in LLC-GA5-COL150 cells. The values of the 50%-inhibitory concentration (IC50) of PSC833 and Cs-A for doxorubicin transport were 0.29 and 3.66 microM, respectively, and those for vinblastine transport were 1.06 and 5.10 microM, respectively. The IC50 of PSC833 for doxorubicin transport was about 4-fold less than that for vinblastine transport, suggesting that the combination of PSC833 and doxorubicin might be effective. PSC833 itself was not transported by P-gp and had higher lipophilicity than Cs-A. These results indicated that the inhibitory effect of PSC833 on P-gp-mediated transport was 5- to 10-fold more potent than that of Cs-A, and this higher inhibitory effect of PSC833 may be related to the absence of PSC833 transport by P-gp and to the higher lipophilicity of PSC833.

Efficacy of repeated percutaneous isolated liver chemoperfusion in local control of unresectable hepatocellular carcinoma.

BACKGROUND/AIMS: Percutaneous isolated liver chemoperfusion (PILP) with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) enables high-dose intraarterial infusion of cytotoxic agents while reducing systemic toxicity. We report here the effect of repeated PILP with HVI-CHP on local control of unresectable hepatocellular carcinoma (HCC). METHODOLOGY: After placement of a hepatic arterial infusion (HAI) catheter, a 4-lumen-2-balloon catheter (24F) was introduced into the retrohepatic inferior vena cava through the femoral vein, and the balloons were inflated to accomplish HVI. During HAI of adriamycin (60-150 mg/m2), total hepatic venous outflow was captured via fenestrations of one major lumen between the balloons and pumped out into CHP filters. The filtered blood was returned to the right atrium through the end opening of another major lumen of the catheter. Of 30 patients, 8 had repeated PILP in a range of 2-4 treatments, and 22 had a single treatment. RESULTS: Eleven (52%) of 21 evaluable patients in the single PILP group and 7 out of 8 patients (88%) in the repeated PILP group had partial or complete response. Median durations of response in responding patients were 6 and 21 months in the single and the repeated PILP groups, respectively (p=0.02). The 1- and 2-year survival rates (single vs. repeated) were 57% vs 88%, and 29% vs 70%, respectively (p=0.05). CONCLUSIONS: Repeated PILP could be performed safely in patients with advanced HCC and significantly prolonged the duration of remission in patients with unresectable HCC.

[A case of multiple colonic liver metastases treated successfully with percutaneous isolated liver chemoperfusion using cisplatin].

We herein report a case of multiple colonic liver metastases treated with repeated percutaneous isolated liver chemoperfusion of cisplatin under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) as an inductive treatment. The patient was a 70-year-old man who underwent curative resections for metachronous rectal and descending colonic cancer in 1979 and 1995, respectively. During outpatient follow-up, he showed increases of serum CEA level. An abdominal CT study demonstrated multiple low-density lesions in the bilateral lobes of the liver, indicating colonic liver metastases. The patient had a total of 2 treatments with percutaneous isolated liver chemoperfusion of cisplatin (total dose, 500 mg) under HVI.CHP. His post-treatment course was uneventful without side effects, including leukopenia and renal dysfunction. Serum CEA levels showed a sharp decrease to 160 ng/ml 3 months after treatment from the pretreatment value of 1,064 ng/ml. CT scan 3 months after treatment revealed remarkable tumor regression along with liquefaction of liver tumors, showing a partial response. These results suggested that repeated percutaneous isolated liver chemoperfusion of cisplatin under HVI.CHP is a potent inductive treatment for patients with multiple colonic liver metastases.

[Efficacy of combined use of sodium thiosulfate in percutaneous isolated liver chemoperfusion of cisplatin under complete hepatic venous isolated and charcoal hemoperfusion].

We herein evaluated the efficacy of combined use of sodium thiosulfate (STS) in isolated liver chemoperfusion of cisplatin (CDDP) under complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 5), CDDP (4 mg/kg) + STS (4 g/body) and group II (n = 5), CDDP (4 mg/kg). In both groups, CDDP was intraarterially administered for 20 minutes under HVI.CHP. In addition, in group I, STS infusion was administered for 20 minutes via the outlet side of CHP filter. The adsorption rates of free and total CDDP of CHP filter were in a range of 50-80%, and the rates in group I were higher than in group II. At all sampling points, the AUC (microgram.min/ml) of free CDDP was not different between the two groups. However, the AUC of total CDDP at postfilter [group I: 35.3 +/- 2.7 (mean +/- SD); group II: 63.5 +/- 21.5] and systemic serum (group I: 24.9 +/- 8.6, group II: 43.5 +/- 13.5) was significantly lower in group I than in group II (p < 0.05). The cumulative amounts of urinary excretion of CDDP (microgram/kg) were 39.5 +/- 12.1 and 13.5 +/- 9.3 in groups I and II, respectively, showing a significant increase in group I (p < 0.01). These results indicated that the use of STS in percutaneous isolated liver chemoperfusion of CDDP under HVI.CHP could further reduce systemic toxicities of CDDP, by increasing CDDP filter extraction of CHP filter and urinary CDDP excretion.

Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors.

BACKGROUND: A single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique. PATIENTS AND METHODS: Sixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter. RESULTS: All patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P < 0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P < 0.01). CONCLUSIONS: The single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Pharmacokinetics of adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation.

We investigated the pharmacokinetics of cytotoxic anticancer agents administered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) or a laparotomy and total hepatectomy under venovenous bypass (anhepatic group, n = 12). Each dog received a bolus intravenous injection of either Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urine concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the plasma Adriamycin concentrations remained persistently higher in the anhepatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group (P < 0.01 vs controls). The renal clearance values did not significantly differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepatic group than in the controls. In a second set of experiments with cisplatin, the plasma platinum concentrations did not significantly differ between the two groups throughout the time course. However, the renal clearance of platinum in the anhepatic dogs showed a fourfold increase compared with that in the controls (P < 0.01). These pharmacokinetic data suggest that Adriamycin carries the risk of increased systemic toxicities, while cisplatin may be associated with increased renal toxicity when administered during the anhepatic period of liver transplantation.

[Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion].

It is difficult to administer an effective dose of cyclosporin A (CsA), a potent inhibitor of P-glycoprotein, to prevent multiple drug resistance due to its side effect. We herein evaluated the efficacy of concomitant use of this agent and complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 4), intraarterial infusion of only adriamycin (ADM) and group II (n = 4), intraarterial infusion of CsA and ADM. In both groups, ADM was intraarterially administered for 10 minutes under HVI.CHP. In addition, in group II, CsA infusion (0.3 mg/min.kg) was initiated 20 min prior to the start of ADM infusion and maintained for 30 min. The AUC (micrograms.min/ml) of ADM were 21.2 +/- 8.6 (mean +/- SD) and 28.4 +/- 10.3 in groups I and II, respectively, at prefilter (hepatic venous level) and 8.1 +/- 4.6 and 4.8 +/- 3.8, respectively, at postfilter, showing an effective drug elimination in both groups. The Cmax (micrograms/ml) were 14.1 +/- 2.2 at prefilter, 2.4 +/- 0.5 at postfilter, and 3.4 +/- 1.2 in systemic level. These results indicated that HVI.CHP allowed the high-dose CsA infusion required for P-gp inhibition in the liver and could reduce extraregional CsA leakage.

[Evaluation of a single catheter technique for percutaneous isolated liver perfusion].

We have established a single catheter technique of percutaneous isolated liver perfusion using a 4-lumen-2-balloon (4L - 2B) catheter for treatment of unresectable malignant liver tumors. Herein reported are the technique, safety and pharmacokinetics of the system in comparison with the original double-balloon technique. This study included 19 patients with malignant liver tumors treated by adriamycin at a dose of 100 mg/m2. Seven patients had the double-balloon technique (group D), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other 12 patients had single catheter technique (group S). In group S, hepatic effluent was solely isolated and directed to CHP filters. All patients except for one in group S showed good hemodynamic stability. The hepatic venous flow rate of group S was significantly higher than in group D (p < 0.05). Although the mean area under the time concentration curve at systemic serum was significantly lower in group S compared to group D, the rate of side effects was similar in both groups. A 4L. 2B single catheter allowed safe and repeated percutaneous isolated liver perfusion for technical simplification of the treatment.

[A case of advanced hepatoma cured by repeated percutaneous isolated liver perfusion using hepatic venous isolation and charcoal hemoperfusion].

We have reported the treatment results of percutaneous isolated liver perfusion using hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) for unresectable liver cancers. This is a case of multiple advanced hepatoma cured completely by repeated per cutaneous isolated liver perfusion. The patient was a 58-year-old woman who was referred to our hospital for a hepatic tumor detected by abdominal computed tomograpy (CT). On admission, she showed HBs antigen positive, mild anemia and liver dysfunction, and elevation of tumor markers. Abdominal CT demonstrated nodular tumors in segment 4. In addition, hepatic angiography additionally revealed multiple bilobar metastases. We treated this case with high-dose intraarterial adriamycin (150 mg/body) using HVI.CHP. There after, the patient received intermittent intraarterial low-dose epirubicin infusions (30 mg/body, 5 times) via an implantable catheter system. Furthermore, she was given a second high-dose of adriamycin (130 mg/body) under HVI.CHP 7 months after the first treatment. Despite repeated high-dose treatments, she had no severe side effects. The levels of tumor markers, including AFP and PIVKA-II, decreased to normal range, and all tumor nodules have disappeared in abdominal CT studies at present, 20 months after the initial treatment. In conclusion, our experience suggests that advanced hepatoma with multiple bilobar lesions, as in this case, would be cured by repeated percutaneous isolated liver perfusion using HVI.CHP.