Imaging of Regional Differences of Muscle Oxygenation during Exercise Using Spatially Resolved NIRS.

The development of imaging systems using near-infrared spectroscopy (NIRS) has enabled noninvasive measurement of regional changes in muscle oxygenation. A spatially resolved NIRS (SR-NIRS) imaging instrument was utilized for real-time measurement of spatial-temporal changes in muscle oxygenation during exercises. Changes in muscle oxygenation and localized O2consumption in the quadriceps muscle were measured during sustained isometric knee extension without and with leg-press to the ground exercises. In the former exercise, the level of tissue oxygen saturation (TOS) of the rectus femoris (RF) muscle was found to be lower than that of vastus lateralis (VL) and vastus medialis (VM) muscles. The highest localized O2consumption rate, VO2, reflecting the localization in distribution of muscle metabolism, was detected in the RF muscle at the initial stage of exercise. As exercise progressed, VO2of the RF muscle decreased whereas that of the VL and VM muscles increased. In contrast, TOS decreased to about the same level for the VL, RF and VM muscles in the latter exercise. Also, VO2of all three muscles decreased as exercise progressed. Initial results demonstrated that the SR-NIRS instrument enables measurement of regional differences in muscle oxygenation in the quadriceps muscle during different exercises.

[A case of multiple hepatocellular carcinoma complicated with N3 regional lymph node metastases preventing tumor progression by gradual introduction of lymph node excision and high-dose chemotherapy using percutaneous isolated hepatic perfusion].

We experienced a case of multiple hepatocellular carcinoma (HCC) complicated with N3 regional lymph node metastases. The gradual introduction of lymph node excision and high-dose chemotherapy using percutaneous isolated hepatic perfusion (PIHP) was effective in preventing progress of the tumor. The patient was a 63-year-old male who underwent a thorough medical examination because of elevated AFP at a local hospital. He was referred to our hospital. The preoperative laboratory results showed the elevation of AFP (729 ng/ml) and PIVKA-II (2,110 mAU/ml). CT scan of the liver revealed tumors in segment 4, 5 and 6, and lymph node metastases from the pancreas to the hepato-duodenal ligament. The enlarged lymph nodes were excised and the tumor in segment 5 was resected for pathological examination. Adriamycin was administered in doses of 100 mg/m2 and 80 mg/m2 using PIHP two and three months after the operation. According to the results of laboratory studies conducted 14 months after the operation, AFP was 12 ng/ml and PIVKA-II was within the normal range. CT scan of the liver showed the liquefaction degeneration of the remaining HCC. Although surgery is not generally indicated in a patient with multiple HCC complicated with N3 regional lymph node metastases, it should be considered in combination with PIHP in those with resectable extrahepatic lesion.

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases.

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100-120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5-15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia < 2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intra-arterial chemotherapy in patients with unresectable hepatic tumors.

Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma.

BACKGROUND: We recently developed a novel system of direct hemoperfusion under hepatic venous isolation in an attempt to achieve high-dose intraarterial chemotherapy for patients with malignant liver tumors. We report here the results of treatment of these patients with advanced hepatocellular carcinoma. METHODS: Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15 patients, under conditions of extracorporeal drug elimination by direct hemoperfusion under hepatic venous isolation. Hepatic venous isolation was accomplished mainly by the double-balloon technique with an occlusion catheter and a balloon catheter. The isolated hepatic venous blood was filtered by direct hemoperfusion and pumped to the left axillary vein. RESULTS: During 5 minutes of adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion filters were 91% +/- 9% (mean +/- SD). The amount of drug removed by the system was 26.4% +/- 16.0% of the amount of drug administered. Two patients died, one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Other side effects included hemolysis related to the system of hemoperfusion (87%), chemical hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor responses, with a median duration of response of 6.2 months. CONCLUSIONS: This approach offers an effective therapeutic option for patients with advanced hepatocellular carcinoma.

[The experimental studies on concomitant occlusion of the superior mesenteric artery during intraarterial chemotherapy of the liver].

We investigated the effect of temporary occlusion of the superior mesenteric artery (SMAO) on the hepatic tissue concentration of anticancer drugs in hepatic artery infusion. Adriamycin (ADR: 1 mg/kg weight) was continuously administered into the hepatic artery for five minutes in dogs. Depending on the use and method of vascular occlusion, animals were allocated into five groups and hepatic tissue ADR levels were determined: Group I, SMAO; Group II, no vascular occlusion; Group III, occlusion of the common hepatic artery (CHAO); Group IV, combined SMAO and CHAO; Group V, occlusion of the portal vein. The hepatic tissue ADR level at 10 minutes was significantly higher in Group I than those in Group II and III. The tissue ADR level in Group IV and V tended to be slightly higher than in Group I, although there is no statistically significant difference. These results indicate that SMAO may provide a useful means of increasing local drug level during regional chemotherapy of the liver.

Direct hemoperfusion under infrahepatic inferior vena caval isolation for the intraarterial chemotherapy of pelvic tumors.

A new simple technique consisting of direct hemoperfusion under infrahepatic inferior vena caval isolation for intraarterial chemotherapy of pelvic tumors is herein described. The inferior vena cava is occluded at the infrahepatic level by means of balloon inflation using a balloon-tipped catheter (16F), which is placed through the right greater saphenous vein. The isolated infrahepatic vena caval blood is withdrawn by a centrifugal pump through a catheter (16F) in the contralateral greater saphenous vein and is filtered by direct hemoperfusion during intraarterial infusion of anticancer drugs. Venous reentry is provided by the central lumen of the balloon-tipped catheter. This procedure was used sequentially on two different occasions to treat a patient with an extensive pelvic tumor. Good hemodynamic stability and a reduction of the systemic drug toxicities were confirmed in both trials. Therefore, we believe that this technique is technically feasible and highly effective in reducing systemic toxicities during high-dose intraarterial chemotherapy for pelvic tumors.

Effect of cold aerobic perfusion on nonparenchymal cell viability of rat livers.

We investigated the effect of oxygen supply on hepatic cellular viability during cold perfusion storage of rat livers. A perfluoro-N-methyldecahydroisoquinoline (FMIQ) emulsion is used as an oxygen carrier. The composition of the perfusate containing 20 w/v% FMIQ is essentially the same as the University of Wisconsin (UW) solution except for the exclusion of hydroxyethyl starch. Rat livers were perfused at 4 degrees C for up to 24 h with either UW solution (group I, oxygenated; group II, unoxygenated) or FMIQ solution (group III, oxygenated; group IV, unoxygenated). After perfusion storage, the livers were reperfused with warm (37 degrees C) oxygenated or cold (4 degrees C) unoxygenated Krebs-Henseleit bicarbonate buffer, and nuclear trypan blue uptake was measured as the index of cell death. With warm oxygenated reperfusion, there remained less than 2% noviable parenchymal cells up to 24 h, regardless of perfusate or oxygenation. In UW-perfused livers, the proportion of nonviable nonprenchymal cells (NPC) increased progressively regardless of oxygenation, the values in groups I and II in the periportal field at 24 h being 39.9 +/- 4.7% (mean +/- SD) and 36.5 +/- 4.2%, respectively. By contrast, in FMIQ-perfused livers, dye uptake by NPC was significantly reduced with oxygenation (16.9 +/- 5.7% and 39.4% +/- 9.1% at 24 h in groups III and IV; P < 0.001). With cold unoxygenated reperfusion, livers in groups I, II, and IV showed a significant decrease of nonviable NPC, while those in group III showed no significant changes. These data indicate that oxygen supply during perfusion storage of the liver may ameliorate lethal injury to NPC precipitated during reperfusion.

Intraarterial infusion of high-dose adriamycin for unresectable hepatocellular carcinoma using direct hemoperfusion under hepatic venous isolation.

A 67-year-old man with an extensive hepatocellular carcinoma (HCC) was treated successfully with intraarterial infusion of high-dose adriamycin (ADR), 150 mg/m2, five minutes continuous infusion using an extra-corporeal system consisting of direct hemoperfusion (DHP) under hepatic venous isolation (HVI). During drug infusion, hepatic effluent was isolated and adsorbed by the DHP for 30 mins. Plasma ADR levels in the radial artery reached a peak of 2.00 micrograms/ml at five mins after the initiation of drug infusion. Peak values at the inlet and outlet of the DHP were 19.71 micrograms/ml and 1.75 micrograms/ml, respectively, indicating substantial drug adsorption by the DHP. The estimated drug removal rate was 31.1%. This treatment led to a marked regression of tumors with tolerable systemic toxicities. Although the patient subsequently died 9 months after treatment of progression of disease, this treatment resulted in a remission of significant duration.

[A comparative study of tumor responses of hepatocellular carcinoma and colorectal hepatic metastasis to cytotoxic anticancer drug].

We investigated the characteristics of tumor responses of hepatocellular carcinoma (HCC, n = 14) and colorectal hepatic metastasis (CHM, n = 10) to high dose hepatic arterial chemotherapy using direct hemoperfusion under hepatic venous isolation. Adriamycin was given at doses ranging from 100 to 150 mg/m2. During drug infusion, two patients with HCC and three with CHM were treated by balloon-occluded arterial infusion (BOAI). Computerized tomographic findings after treatment were compared between the two diseases. In addition, response characteristics in each disease were investigated in relation to tumor factors such as size, capsule formation, vascularity and macroscopic type. Eight (57%) out of 14 patients with HCC showed either size reduction (n = 5) or liquefaction (n = 3), while the remaining six patients showed no apparent changes. On the other hand, seven (70%) of 10 patients with CHM showed liquefaction without any evidence of tumor size reduction. Regardless of the disease, all patients treated with BOAI had liquefaction as a sign of tumor responses. Based on these observations, it is concluded that response characteristics may differ depending on tumor factors such as vascularity and the nature of the treatment as represented by BOAI.

[Comparison of hepatic tissue extraction rates of cytotoxic anticancer drugs during hepatic arterial chemotherapy--evaluation using direct hemoperfusion under hepatic venous isolation].

Hepatic extraction rates (ER) of anticancer drugs during hepatic arterial infusion were investigated with the aid of direct hemoperfusion (DHP) under hepatic venous isolation (HVI). Using mongrel dogs (n = 6), adriamycin (ADR), mitomycin C (MMC) and cisplatin (CDDP) were simultaneously administered to the hepatic artery at each dosage of 1 mg/kg in 10 minutes under HVI.DHP. Hepatic venous flow and plasma concentrations of each drug at the carotid artery, the inlet and outlet sides of DHP were periodically determined during HVI.DHP. Based on these data, drug adsorption and removal rates were estimated. In addition, hepatic tissue uptakes of each drug were calculated from the amounts of drug administered and leaked in the hepatic effluent. Subsequently, the percentage of tissue uptake of each drug to the amount of drug administered was determined as ER of each drug. Drug adsorption rates during the first 10 minutes after infusion showed no significant difference among three drugs. Drug removal rate of CDDP tended to be higher than those of other two drugs. ER of CDDP (54.8 +/- 18.3%) were significantly lower (p < 0.01) as compared to ADR (84.4 +/- 16.2%) and MMC (83.1 +/- 15.7%). These results indicate that ER of each drug should be taken into consideration to determine appropriate drug for hepatic arterial chemotherapy.