Use of a Glass Membrane Pumping Emulsification Device Improves Systemic and Tumor Pharmacokinetics in Rabbit VX2 Liver Tumor in Transarterial Chemoembolization.

PURPOSE: To evaluate the phamacokinetics of epirubicin in conventional transarterial chemoembolization using a developed pumping emulsification device with a microporous glass membrane in VX2 rabbits. MATERIALS AND METHODS: Epirubicin solution (10 mg/mL) was mixed with ethiodized oil (1:2 ratio) using the device or 3-way stopcock. Forty-eight rabbits with VX2 liver tumor implanted 2 weeks prior to transarterial chemoembolization were divided into 2 groups: a device group (n = 24) and a 3-way-stopcock group (n = 24). Next, 0.5 mL of emulsion was injected into the hepatic artery, followed by embolization using 100-300-µm microspheres. The serum epirubicin concentrations (immediately after, 5 minutes after, and 10 minutes after) and the tumor epirubicin concentrations (20 minutes after and 48 hours after) were measured after transarterial chemoembolization. Histopathologic evaluation was performed with a fluorescence microscope. RESULTS: The area under the curve and maximum concentrations of epirubicin in plasma were 0.45 ± 0.18 µg min/mL and 0.13 ± 0.06 µg/mL, respectively, in the device group and 0.71 ± 0.45 µg min/mL and 0.22 ± 0.17 µg/mL, respectively, in the 3-way-stopcock group (P = .013 and P = .021, respectively). The mean epirubicin concentrations in VX2 tumors at 48 hours in the device group and the 3-way-stopcock group were 13.7 ± 6.71 and 7.72 ± 3.26 µg/g tissue, respectively (P = .013). The tumor necrosis ratios at 48 hours were 62 ± 11% in the device group and 51 ± 13% in the 3-way-stopcock group (P = .039). CONCLUSIONS: Conventional transarterial chemoembolization using the pumping emulsification device significantly improved the pharmacokinetics of epirubicin compared to the current standard technique using a 3-way stopcock.

Transarterial- chemoembolization remains an effective therapy for intermediate-stage hepatocellular carcinoma with preserved liver function.

AIM: To evaluate outcomes as well as prognostic factors of transarterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma (HCC) with preserved liver function to determine positioning of TACE. METHODS: Of 158 treatment-naïve patients with intermediate-stage HCC who received initial TACE from February 2007 to January 2016, 113 patients met the following inclusion criteria: no combined therapy within 4 weeks after initial TACE, and Child-Pugh score under 7. Response rate and overall survival were evaluated. The prognostic factors were investigated in univariate and multivariate analyses using Cox proportional hazards models. The deterioration of liver function after repeated TACE was also evaluated. RESULTS: The response rate was 92.7% (complete response, 63.3%; partial response, 29.4%). The median survival time was 45.2 months. Survival rates at 1, 2, and 3 years were 90.4%, 77.0%, and 60.8% respectively. Age ≥ 75 years (P = 0.022), serum α-fetoprotein level ≥ 200 ng/mL (P = .010), tumor number ≥ 11 (P = 0.008), and heterogeneous enhancement on dynamic computed tomography (P = 0.024) were poor prognostic factors. The deterioration rate of Child-Pugh score and albumin-bilirubin grade was 18.5% and 12.3%, respectively, after the first TACE, 15.6% and 5.1%, respectively, after the second TACE, and 14.5% and 11.1%, respectively, after the third TACE. CONCLUSION: Superselective TACE can achieve high tumor response rates with prolonged overall survival for patients with intermediate-stage HCC with preserved liver function. Age, serum α-fetoprotein level, tumor number ≥ 11, and heterogeneous enhancement on dynamic computed tomography indicated significantly poor prognosis.

Selective TACE with irinotecan-loaded 40 µm microspheres and FOLFIRI for colorectal liver metastases: phase I dose escalation pharmacokinetic study.

BACKGROUND: Efficacy of treatments for colorectal liver metastases after failure of first-line chemotherapy is limited. The aim of this study was to prospectively evaluate the feasibility, tolerability, and pharmacokinetics of selective transarterial chemoembolization (TACE) with irinotecan-loaded 40 µm microspheres combined with systemic FOLFIRI for colorectal liver metastases refractory to oxaliplatin regimen. METHODS: The dose escalation study was conducted in three patient groups with different amounts of irinotecan loaded (50, 75 and 100 mg per mL-microspheres). Selective catheterization was performed to embolize subsegments or segments of located tumors using TACE navigation system. FOLFIRI was administrated 7 days after TACE. Plasma concentration was measured before and time points after administration. RESULTS: Nine patients successfully underwent a total of 22 TACE procedures. Dose-limiting toxicity did not appear at any level. The overall response rate was 55.6%. The median progression free and overall survival were 8.1 and 18.2 months, respectively. The AUC and Cmax of plasma SN-38 per 1 mg injected irinotecan dose were significantly higher in irinotecan-loaded microspheres compared with FOLFIRI (P = 0.009 and P <  0.001, respectively). CONCLUSION: Selective TACE using 40 µm irinotecan-loaded microspheres combined with systemic FOLFIRI was feasible and safe even when a high dose of irinotecan was loaded. Irinotecan-loaded microspheres resulted in a higher plasma concentration and AUC of SN-38 than treatment with FOLFIRI. Further large scale trials to evaluate the efficacy are mandatory. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, Registration number; UMIN000015367 ; Registered date; 08,10,2014.

Development of pumping emulsification device with glass membrane to form ideal lipiodol emulsion in transarterial chemoembolization.

PURPOSE: To evaluate a pumping emulsification device that can improve the physiochemical properties and stability of lipiodol emulsion for conventional transarterial chemoembolization. MATERIALS AND METHODS: A pumping emulsification device constructed of a glass membrane with a hydrophobic surface with pore size of 50 µm in diameter was placed between two syringe adaptors. Epirubicin solutions were mixed with lipiodol with pumping exchanges using the emulsification device or a three-way cock. The ratios of epirubicin solution to lipiodol were 1:2 or 1:1. A total of 120 emulsions were created. RESULTS: The emulsification device showed significantly higher percentages of water-in-oil when compared with the three-way cock (97.9 % vs. 68.9 % in 1:2 ratio, and 82.1 % vs. 17.8 % in 1:1 ratio, p < .001). Droplet sizes in the emulsification device were more homogenous. Mean droplet sizes and viscosities in the emulsification device did not show any significant changes for 30 min after pumping, whereas in the three-way cock, the droplet sizes significantly enlarged and viscosities significantly decreased (p=.023 and p=.002). CONCLUSION: The emulsification device can form a high percentage of water-in-oil emulsion with stable droplets sizes and viscosities. This developed device is promising to increase therapeutic effects in conventional transarterial chemoembolization. KEY POINTS: • We developed new device for transarterial chemoembolization for liver cancer. • The device can improve the physiochemical properties of lipiodol emulsion. • The device can increase the therapeutic effects in conventional transarterial chemoembolization.

Techniques to Form a Suitable Lipiodol-Epirubicin Emulsion by Using 3-Way Stopcock Methods in Transarterial Chemoembolization for Liver Tumor.

PURPOSE: To compare physicochemical properties of emulsions of ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and epirubicin prepared using different techniques for conventional transarterial chemoembolization. MATERIALS AND METHODS: Lipiodol was mixed with epirubicin solution (8.33 mg/mL) by using a 3-way stopcock. The following technical parameters were compared: ratio of epirubicin solution to Lipiodol (1:2 vs 1:1), number of pumping exchanges through the stopcock (20 exchanges vs 10 exchanges), pumping speed (1 s/push vs 2 s/push), and first push syringe (epirubicin solution vs Lipiodol). RESULTS: The mean percentage of water-in-oil was 70.45 ± 1.51 in the 1:2 epirubicin-Lipiodol ratio and 16.03 ± 2.95 in the 1:1 ratio (P < .001). The first push syringe did not influence emulsion type. Median droplet sizes were significantly larger in the slower pumping speed (52.0 µm in 2 s vs 33.7 µm in 1 s; P < .001), whereas there was no significant difference in number of pumping exchanges. Droplet sizes enlarged during 30 minutes after pumping. Viscosity was lower in the 1:1 ratio and the slower pumping speed. Viscosity decreased during 30 minutes after pumping. CONCLUSIONS: The ratio of epirubicin to Lipiodol is a significant factor to form water-in-oil emulsions with higher viscosity. The percentage of water-in-oil is limited to 70% using current pumping techniques. The pumping speed strongly influences droplet size and viscosity.

Intraarterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rabbit Liver Tumor Model.

PURPOSE: To evaluate the pharmacokinetics of intraarterial (IA) administration of micellar nanoparticles incorporating SN-38 injection compared with intravenous (IV) administration in a rabbit liver tumor model. MATERIALS AND METHODS: In this animal care committee-approved study, 18 rabbits (mean weight, 3.89 kg; range, 3.20-4.70 kg) with VX2 liver tumors were divided into two groups (IA and IV). Micellar nanoparticles incorporating SN-38 (30 mg/kg) were injected through the left hepatic artery in the IA group and the right femoral vein in the IV group. NK012 and free SN-38 in the plasma, liver parenchyma, and tumors were measured within 24 hours. Histologic examinations were conducted at 2 and 24 hours. RESULTS: There were no significant differences in the serum area under the concentration-time curve (0-24 h) for free SN-38, at 1,500 and 1,310 µg∙min/mL in the IA and IV groups, respectively (P = .152). The IA group showed significantly higher free SN-38 concentrations in tumor tissues at all time points compared with the IV group (P = .002 at 3 min, P = .011 at 2 h, and P = .047 at 24 h). Histologic findings showed that significantly higher tumor necrosis ratios were observed in the IA group compared with the IV group at 24 hours (P = .028). CONCLUSIONS: Micellar nanoparticles could be a promising IA drug delivery system to achieve high tumor tissue concentrations of SN-38.

Coils versus gelatin particles with or without intraarterial antibiotics for partial splenic embolization: a comparative evaluation.

PURPOSE: To compare the efficacy, complications, and inflammatory levels in partial splenic embolization (PSE) with coils or gelatin sponge (GS) particles with or without intraarterial antibiotic agents. MATERIALS AND METHODS: Forty-four patients with hypersplenism treated by PSE were assessed. GS particles were used in 31 patients, and coils were used in 13 patients. In 17 of the 31 patients who received GS, GS suspended in antibiotic solution was injected via the splenic artery. In the other 14 patients, antibiotic agents were not used. In all 13 coil group patients, an antibiotic solution was intraarterially injected before embolization. Platelet counts were compared between the GS and coil groups. Complications and serum C-reactive protein (CRP) levels were compared among the three groups. RESULTS: There were no significant differences in platelet counts and platelet increased ratios at 6 months (10.0 × 10(4)/µL and 193% in the GS group vs 9.0 × 10(4)/µL and 221% in the coil group), and no significant differences in frequencies of complications. However, one splenic abscess occurred in a patient treated with GS without antibiotics, resulting in death. The mean serum CRP level in the GS with antibiotic group at 2 weeks was significantly lower than in the other two groups. CONCLUSIONS: The efficacy of PSE is similar with the use of coils versus GS particles. Prophylactic intraarterial antibiotic treatment could be useful in preventing inflammatory reactions after PSE.

Pharmacokinetics and antitumor efficacy of chemoembolization using 40 µm irinotecan-loaded microspheres in a rabbit liver tumor model.

PURPOSE: To evaluate the pharmacokinetics and antitumor efficacy of 40 µm irinotecan-loaded drug-eluting microspheres (Embozene TANDEM Microspheres; CeloNova BioSciences, Inc, San Antonio, Texas) (TANDEM-IRI). MATERIALS AND METHODS: The following three groups included eight VX2 rabbits each: group 1, full-loaded (50 mg irinotecan/1 mL TANDEM)/high-dose injection (1 mg irinotecan/kg); group 2, full-loaded (50 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg); and group 3, half-loaded (25 mg irinotecan/1 mL TANDEM)/low-dose injection (0.5 mg irinotecan/kg). Irinotecan and SN-38 in the plasma and tumors were measured within 72 hours. Histologic examinations were conducted on days 1, 3, and 7. RESULTS: Serum irinotecan levels remained near the maximum concentration for 180 minutes after transarterial chemoembolization; in group 1, levels were 351.4 ng/mL at 30 minutes, 329.0 ng/mL at 60 minutes, and 333.5 ng/mL at 180 minutes. The area under the curve for 0-24 hours of irinotecan in group 1 was approximately two times higher than the same value in groups 2 and 3. High irinotecan and SN-38 concentrations in the tumors were measured at 24 hours and 72 hours. After transarterial chemoembolization, levels of liver enzymes aspartate aminotransferase and alkaline phosphatase were significantly higher in group 1 compared with groups 2 and 3. Histologic findings showed microspheres had deeply penetrated into tumors. Significantly higher tumor necrosis ratios were observed in groups 1 (86.6%-90.0%) and 3 (90.0%-100%) compared with group 2 (63.3%-70%) (P = .031 and P = .016). CONCLUSIONS: Slow drug release with high drug concentration in tumors can be provided with 40 µm TANDEM-IRI. When complete arterial embolization is performed, the dose of irinotecan loaded on 40 µm TANDEM microspheres can be reduced while maintaining efficacy.

Percutaneous Trans-jejunum Pancreatojejunostomy Reconstruction for Intractable Pancreatic Fistula after Pancreatoduodenectomy.

We present an interventional radiology technique for percutaneous trans-jejunal pancreatojejunostomy reconstruction for intractable pancreatic fistula. A 70-year-old man with pancreatic cancer who had undergone pancreatoduodenectomy underwent percutaneous drainage for leakage from the anastomosis of the pancreatic duct to the jejunum. The leakage continued and the hole at the anastomosis site in the jejunum closed completely after 5 months. We performed percutaneous jejunostomy; the previously placed drainage catheter was then replaced with a balloon catheter, which was punctured by a 19-gauge needle from inside the jejunum through the percutaneous jejunostomy tube. The seeking catheter was inserted into the pancreatic duct. Finally, a side-holed 6-Fr straight catheter was successfully placed in the pancreatic duct through the percutaneous jejunostomy route.

[A case of radiofrequency ablation with hepatic venous balloon occlusion and transient hepatic arterial embolization using degradable starch microspheres for a large well-differentiated hepatocellular carcinoma].

A 70-year-old man with liver cirrhosis due to hepatitis C viral infection had a single well-differentiated hepatocellular carcinoma(HCC) of 5-cm diameter in the right superior anterior segment of the liver. Surgery could not be performed because of his poor liver function. Furthermore, it was difficult to treat this tumor with transcatheter arterial chemoembolization because the tumor exhibited hypovascularity. Radiofrequency ablation (RFA) alone was also not an option because the tumor was too large to manage with a simple RFA procedure. This solitary tumor was adjacent to the right and middle hepatic veins. Finally, we planned to treat this tumor with RFA and temporary vessel occlusion as follows: RFA was performed with a 5-cm expandable type RITA model 90 electrode under temporary occlusions of the right anterior hepatic artery with degradable starch microspheres, and of the right and middle hepatic veins by balloon catheters, to reduce the heat sink effect and obtain a larger coagulation size. We successfully treated this HCC with RFA combined with temporary vessel occlusion, and the patient has not obtained local recurrence at 18 months of the procedure.

[Initial experience of transcatheter arterial chemolipiodolization with miriplatin for recurrent hepatocellular carcinoma].

OBJECTIVE: Miriplatin(MP) is a promising newly developed anticancer agent for transcatheter arterial chemoinfusion in patients with hepatocellular carcinoma(HCC), particularly those previously not treated with chemotherapy. The aim of this study was to assess the efficacy and safety of transarterial chemolipiodolization with MP for recurrent HCC in patients previously treated with chemotherapy. MATERIALS AND METHODS: From January 2010 to March 2011, 17 patients with recurrent HCC were treated with MP via a transcatheter arterial approach. The dose of MP per treatment session was up to 140 mg. We repeated this treatment protocol until tumor progression occurred. We assessed the therapeutic results and the adverse events. RESULTS: MP was infused at a dose of 60-140 mg in the initial treatment session; the mean treatment session number was 1.8; and the total dose of MP was 60-400 mg (median, 120 mg). Response rate and disease control rate after the initial treatment were 17.6% and 47.1%,respectively. Response rate and disease control rate after the total treatment session were 17.6% and 29.4%,respectively. Median tumor-free survival was 86 days. We encountered a severe adverse event in 1 patient who died due to his concomitant disease( diabetic nephropathy and radiation hepatitis) 38 days after this protocol. CONCLUSION: The therapeutic result of MP was unsatisfactory, but adverse events due to MP infusion, including renal and/or liver damage, were minor.

Arterial Embolization Using Microspheres for Hypervascular Liver Metastases Refractory to Standard Treatments: A Multicenter Prospective Clinical Trial.

PURPOSE: To evaluate the clinical utility of bland arterial embolization using microspheres in patients with hypervascular liver metastases refractory to standard treatments. MATERIALS AND METHODS: Primary endpoints of this prospective single-arm non-comparative study were objective response and disease control rates (ORR and DCR), based on the modified Response Evaluation Criteria in Solid Tumors at 4 weeks after embolization. Secondary endpoints were ORR according to primary tumor, overall survival, progression-free survival (PFS), and safety. RESULTS: Twenty-five patients with a median age of 66 years (range, 40-95 years) were enrolled in this study. The median maximum diameter of liver metastasis was 3.7 cm (range, 2.0-15.2 cm). Primary lesions were colorectal cancer in 12 patients (48%, 12/25), other cancer in 7 (28%, 7/25), neuroendocrine tumor in 4 (16%, 4/25), and sarcoma in 2 (8%, 2/25). ORR and DCR were 52% (13/25) and 72% (18/25) in all patients, 42% (5/12) and 75% (9/12) in colorectal cancer patients, and 62% (8/13) and 69% (9/13) in other malignant tumor patients (p = 0.43, p > 0.99). Median survival time was 19 months in all patients, 19 months in colorectal cancer patients, and 8 months (p = 0.16) in other malignant tumor patients. Median PFS time was 4 months in all patients, 4 months in colorectal cancer patients, and 6 months (p = 0.0085) in other malignant tumor patients. There were no grade-3 or -4 adverse events. CONCLUSION: Microsphere embolization appears to be an effective and safe treatment for hypervascular liver metastases refractory to standard treatments.

Efficacy of a Glass Membrane Emulsification Device to Form Mixture of Cisplatin Powder with Lipiodol on Transarterial Therapy for Hepatocellular Carcinoma.

PURPOSE: To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock. MATERIALS AND METHODS: Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion). RESULT: The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52 min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8 min (P = 0.046-0.050). Suspension showed the longest release time; however, the viscosity was lowest. CONCLUSION: The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.

[Locally advanced pancreatic cancer successfully treated by arterial infusion chemotherapy combined with stereotactic radiotherapy--a case report].

We report a 60-year-old female with locally advanced pancreatic cancer successfully treated with stereotactic radiotherapy after arterial chemoinfusion. Using the indwelling catheter-port system with the unification of the pancreatic blood supply, we initially conducted an arterial infusion of weekly high-dose 5-FU (1,000 mg/m2/qw) combined with systemic gemcitabine (1,000 mg/m2/qw). As a result, the tumor was remarkably decreased. However, a part of the tumor where the drug had not been distributed remained in no reduction. Therefore, we added the stereotactic radiotherapy (50 Gy) targeted on the limited residual tumor and combined with concurrent systemic gemcitabine (1,000 mg/m2/qw). The residual tumors have been controlled well without distant metastases, and the patient is alive today 36 months after our initial treatment.

Improved Local Tumor Control and Survival Rates by Obtaining a 3D-Safety Margin in Superselective Transarterial Chemoembolization for Small Hepatocellular Carcinoma.

OBJECTIVE: To investigate technical factors affecting local tumor control of small hepatocellular carcinoma (HCC) treated by superselective conventional transarterial chemoembolization (cTACE) using lipiodol and to compare prognoses between groups with and without these factors. MATERIALS AND METHODS: Sixty-three consecutive patients with 73 HCC nodules (diameter, 1-3 cm) treated by cTACE were retrospectively analyzed. A positive or a negative 3D-safety margin was defined as a ≥ 1-mm area of lipiodol accumulation or as a diameter of lipiodol accumulation < 1 mm in liver parenchyma surrounding the tumor using plain CT images obtained within a week after TACE. Uni- and multivariate analyses were performed to identify technical factors determining local tumor control rate. Subgroup analysis of survival rates in treatment-naïve patients was performed according to the detected factors. RESULTS: In univariate analyses, three-dimensional (3D)-safety margin and portal vein visualization were associated with local tumor control rates. In multivariate analysis, only positive 3D-safety margin remained a significant contributor (p = 0.001). Two-year cumulative local disease-free survival rates with positive and negative 3D-safety margin were 82.8% and 19.3%, respectively (p = 0.001). In subgroup survival analysis of the 36 newly diagnosed patients, the 1-, 2-, 3-, 4-, and 5-year cumulative OS rates for patients with and without positive margins were 100% versus 100%, 96.4% versus 75.0%, 81.8% versus 62.5%, 74.4% versus 41.7%, and 47.0% versus 0%, respectively (median survival time; 57.6 months vs. 37.1, p = 0.047). CONCLUSION: Obtaining a 3D-safety margin can suppress local tumor recurrence and prolong survival in superselective cTACE for small HCC.

Drug Release Property of Lipiodol Emulsion Formed by Glass Membrane Emulsification Device for Transarterial Chemoembolization.

PURPOSE: To evaluate physiochemical characteristics of emulsions formed by a modified emulsification device and to compare in vitro drug release properties of ethiodized oil (Lipiodol)-drug solution emulsion formed by the device and a 3-way-stopcock for conventional transarterial chemoembolization. MATERIALS AND METHODS: A V-shaped pumping emulsification device with a 100-µm-micropore glass membrane was developed to reduce the resistance of pumping. Epirubicin solution was mixed with Lipiodol (ratio 1:2) with pumping exchanges through the device. The percentage of water-in-oil (W/O) and droplet size distribution and viscosity were evaluated. The in vitro drug release properties were compared between using the device and a 3-way-stopcock. RESULTS: Percentage of W/O was 98.45 ± 0.03%. The median droplet size was 22.58 ± 1.70 µm, and the viscosity was 143.70 ± 12.36 cP. The released epirubicin at 0 min was 1.73 ± 1.05% in the device, whereas 41.02 ± 7.27% in a 3-way-stopcock (P < 0.001). The half-life of release (t50%) of the device was significantly longer than that of a 3-way-stopcock (175 ± 25 vs. 8 ± 6 min, P < 0.001). CONCLUSION: The V-shaped emulsification device with a 100-µm-micropore glass membrane can form nearly 100% W/O emulsion with homogenous droplet sizes. Emulsion formed by the device showed a slower epirubicin release property compared with that of a 3-way-stopcock.

Development of Repeatable Microcatheter Access Port for Intra-arterial Therapy of Liver Cancer.

PURPOSE: To develop an implantable port in which a microcatheter can be inserted for a combination therapy of repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer. MATERIALS AND METHODS: The design of a currently used implantable port was modified. A funnel part was constructed in the port. The septum was punctured by a 20-gauge indwelling needle, and 2.0-Fr non-tapered microcatheter was inserted into the port. In the in vitro studies, the advance of a microcatheter out of the funnel part was evaluated via seven different septum puncture sites. A 5-Fr indwelling catheter connected to the port was placed in a vascular model, and a microcatheter catheterization was evaluated. In an in vivo study, the port-catheter system was implanted in the hepatic artery in a pig. A microcatheter was percutaneously inserted through the port into the hepatic arterial branches, and embolization was performed. RESULTS: In the in vitro studies, the microcatheter was smoothly advanced out of the port and catheterizations into the hepatic arteries were successful via all septum puncture sites. In the in vivo study, repeated selective embolization through the port was successfully conducted on 7, 14 and 21 days after the implantation. CONCLUSION: The developed implantable port can be used for repeated catheter insertion into the hepatic artery. The combination of repeated TACE and HAIC could be possible using this device.

Safety and Prognosis of Transarterial Chemoembolization for Octogenarians with Hepatocellular Carcinoma.

PURPOSE: The global population of the aged is escalating. The need of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients older than 80 years is on the rise. The aim of this study was to retrospectively evaluate the safety and the prognosis of TACE in octogenarians with HCC. MATERIALS AND METHODS: From January 2007 to January 2018, 86 octogenarians with HCC initially treated with TACE, who were treatment naïve or had a recurrence after surgery and/or radiofrequency ablation, were enrolled in this study. The adverse events were evaluated. The overall survival (OS) after TACE and causes of death were investigated. The prognostic factors for OS were analyzed using Cox proportional hazard models. RESULTS: Grade 4 adverse events (according to the Common Terminology Criteria for Adverse Event version 4.0) of AST, ALT and tumor rupture were found in 8, 4 and 1 patients, respectively. There were no treatment-related deaths. The 1-, 3- and 5-year overall survival rates were 84.1%, 61.1% and 27.6%, respectively. The overall median survival time was 38.3 months (HR 2.854, 95% CI 32.7-43.8). 56.9% causes of death were HCC or liver dysfunction. Multivariate analysis revealed that performance status (ECOG: 0) was an independent prognostic significant factor (95% CI 1.103-4.573; P = .026). CONCLUSIONS: TACE is safe and could improve survival of octogenarians with HCC. Performance status is an important prognosis factor predicting the OS.

Superabsorbent Polymer Microspheres Prepared with Hypertonic Saline to Reduce Microsphere Expansion.

PURPOSE: To analyze size changes of superabsorbent polymer (SAP) microspheres with the reduced expansion technique, and to evaluate pharmacological advantages of transarterial chemoembolization using cisplatin-loaded SAP microspheres with the reduced expansion technique. MATERIALS AND METHODS: In an in vitro study, diluted contrast materials containing different concentrations of sodium ions were examined to expand SAP microspheres and determined the reduced expansion technique. Size distributions of cisplatin-loaded SAP microspheres were analyzed. In an in vivo study, TACE was performed using cisplatin-loaded SAP microspheres with the reduced expansion and control techniques in 18 VX2 rabbits. RESULTS: The degree of expansion was reduced to the greatest extent by using a mixture of non-ionic contrast material and 10% NaCl at a 4:1 ratio. The mean diameter of the reduced expansion of cisplatin-loaded SAP microspheres was 188.4 µm, while that of the control expansion was 404.9 µm. The plasma platinum concentrations of the reduced expansion group at 5 min after TACE were significantly higher than those of the control expansion group (2.19 ± 0.77 vs. 0.75 ± 0.08 µg/mL, P = .01). The tumor platinum concentrations of the reduced expansion group at 1 h were significantly higher than those of the control expansion group (10.76 ± 2.57 vs. 1.57 ± 0.14 µg/g, P = .044). CONCLUSION: The expanding level of SAP microspheres can be reduced by using hypertonic saline. Cisplatin-loaded SAP microspheres with the reduced expansion technique have the advantages of achieving higher cisplatin tissue concentration in TACE for liver tumors.

Preoperative identification of subthalamic nucleus for deep brain stimulation using three-dimensional phase sensitive inversion recovery technique.

PURPOSE: We assessed the feasibility of utilizing three-dimensional (3D) phase sensitive inversion recovery (IR) images for preoperatively determining deep brain stimulator position. METHODS: We measured geometric distortion with a grid phantom and evaluated images of 3 volunteers to determine optimum imaging parameters for 3D phase sensitive IR. RESULTS: Geometric distortion measured less than 1.0%. Respective inversion and recovery times, which provided high T(1) contrast between the subthalamic nucleus and adjacent tissue, were 200 and 4000 ms. In studies of 3 volunteers and 2 patients, the subthalamic nucleus was clearly depicted in 3D phase sensitive IR images. The measured coordinates of the subthalamic nucleus agreed well with those calculated by conventional estimation from midpoint of the anterior and posterior commissure. CONCLUSION: Three-dimensional phase sensitive inversion recovery was useful in visualizing the subthalamic nucleus for effective deep brain stimulation.