Satoru Murata

To evaluate the relationship between the location of hepatocellular carcinoma (HCC) and the efficacy of transarterial chemoembolization (TACE). We evaluated 115 patients (127 nodules), excluding recurrent nodules, treated with TACE between January 2011 and June 2014. TACE efficacy was evaluated according to mRECIST. The HCC location coefficient was calculated as the distance from the central portal portion to the HCC center (mm)/liver diameter (mm) on multiplanar reconstruction images rendered (MPR) to visualize bifurcation of the right and left branches of the portal vein and HCC center. The HCC location coefficient was compared between complete response (CR) and non-CR groups in Child-Pugh grade A and B patients. The median location coefficient of HCC among all nodules, the right lobe, and the medial segment was significantly higher in the CR group than in the non-CR group in the Child-Pugh grade A patients (0.82 vs 0.62, P < 0.001; 0.71 vs 0.59, P < 0.01; 0.81 vs 0.49, P < 0.05, respectively). However, there was no significant difference in the median location coefficient of the HCC in the lateral segment between in the CR and in the non-CR groups (0.67 vs 0.65, P > 0.05). On the other hand, in the Child-Pugh grade B patients, the HCC median location coefficient in each lobe and segment was not significantly different between in the CR and in the non-CR groups. Improved TACE efficacy may be obtained for HCC in the peripheral zone of the right lobe and the medial segment in Child-Pugh grade A patients.

To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. • Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. • Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. • Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma.

To evaluate the feasibility of a novel embolization technique, the Amplatzer vascular plug (AVP) anchoring technique, to stabilize the delivery system for microcoil embolization. Three patients were enrolled in this study, including two cases of internal iliac artery aneurysms and one case of internal iliac arterial occlusion prior to endovascular aortic repair. An AVP was used in each case for embolization of one target artery, and the AVP was left in place. The AVP detachment wire was then used as an anchor to stabilize the delivery system for microcoil embolization to embolize the second target artery adjacent to the first target artery. The microcatheter for the microcoils was inserted parallel to the AVP detachment wire in the guiding sheath or catheter used for the AVP. The AVP anchoring technique was achieved and the microcatheter was easily advanced to the second target artery in all three cases. The AVP anchoring technique was found to be feasible to advance the microcatheter into the neighboring artery of an AVP-embolized artery.

The percutaneous isolated pancreas perfusion technique at an infusion rate of 40 mL/min appears to be safe and feasible for perfusion of the pancreas with 1.5 mg of cisplatin per kilogram of body weight. PurposeTo evaluate the feasibility of percutaneous isolated pancreas perfusion (PIPP) by using a pig model.Materials and MethodsAll experiments were approved by the institutional Animal Experiment Ethics Committee. Fifteen pigs were assigned to five groups, and PIPP was performed. Angiographic and dye injection studies were performed to confirm the patency of the PIPP system (group 1). Blood that contained cisplatin (1.5 mg per kilogram of body weight) in an extracorporeal circuit was circulated through the pancreas at three infusion rates (40, 60, and 80 mL/min) to determine the optimal infusion rate in terms of safety and pharmacologic effectiveness (groups 2, 3, and 4, respectively). Chronological laboratory data and histologic findings were assessed in group 5, which received the optimal infusion rate. Maximum platinum concentration (Cmax) and area under the platinum concentration–time curve were compared by using the Kruskal-Wallis and Mann-Whitney U tests.ResultsAngiography and dye injection confirm...

Second-line therapy has limited activity in patients with recurrent or persistent uterine cervical cancer that has progressed after chemoradiation and palliative chemotherapy. The purpose of this study was to evaluate the efficacy of negative-balance isolated pelvic perfusion (NIPP) in patients with pretreated recurrent/persistent uterine cervical cancer. Between April 2004 and May 2013, a total of 26 patients with recurrent or persistent uterine cervical cancer previously treated with platinum-based systemic chemotherapy and/or chemoradiotherapy received NIPP therapy at our institution, consisting of a 30-min isolated pelvic perfusion with cisplatin and fluorouracil, followed by isolated pelvic dialysis. Primary endpoints were response rate (RR) and progression-free survival (PFS), while secondary endpoints were overall survival (OS) and safety. Platinum pharmacokinetics were also evaluated. The RR was 57.7 % (complete response, five patients; partial response, ten patients). The median PFS and OS after NIPP therapy were 11.0 (95 % confidence interval [CI] 6.6–15.4) and 25.1 (95 % CI 17.1–33.1) months, respectively. PFS was significantly better in patients without intestinal involvement (p = 0.016) or dissemination (p NIPP appears to be an effective and feasible method for patients with pretreated recurrent or persistent cervical cancer.

This study aimed to evaluate the feasibility and underlying pharmacokinetics of the retrograde-outflow technique for percutaneous isolated hepatic perfusion (PIHP). Retrograde-outflow PIHP was performed in 12 male pigs (weight, 37–44 kg) by redirecting hepatic outflow through the portal vein. Blood with cisplatin (2.5 mg/kg) in an extracorporeal circuit was circulated through the liver under isolation using rotary pumps with balloon catheters. Hepatic angiographic examinations were conducted during perfusion, and histopathological examinations of the organs were conducted after perfusion. The maximum platinum concentration (C _max), area under the concentration-time curve (AUC), and chronologic laboratory data were measured. Retrograde-outflow isolated hepatic angiography confirmed that contrast media flowed into the portal veins in all 12 pigs. The hepatic veins and inferior vena cava were not opacified. Hepatic C _max (86.3 mg/l) was 39-fold greater than systemic C _max (2.2 mg/l), and hepatic AUC (1330.8 min · mg/l) was 30-fold greater than systemic AUC (44.6 min · mg/l). Histopathological examinations revealed no ischaemic changes or other abnormalities in the liver, duodenum, small intestine, or colon. Within 1 week of the procedure, chronologic laboratory data (n = 3) normalized or returned to pre-therapy levels. The retrograde-outflow technique appears to enable safe and feasible PIHP therapy. • The portal vein acted as an outflow tract under retrograde-outflow PIHP. • Plasma hepatic-to-systemic exposure ratio was 39.2 for the maximum platinum concentration. • Plasma hepatic-to-systemic exposure ratio was 29.8 for the AUC. • The retrograde-outflow technique appears to enable safe and feasible PIHP.

Background: Drug leakage and lack of a drug-removal system have prevented clinical application of isolated pelvic perfusion (IPP). These barriers were overcome with negative-balance IPP (NIPP) in experimental pig models. Here, a phase 1 clinical study of NIPP was performed in patients with incurable symptomatic rectal cancer. Purpose: To establish a safe regimen of high-dose regional chemotherapy with NIPP using cisplatin in patients with incurable rectal cancer. Material and Methods: Between June 2004 and January 2007, NIPP therapy was performed for 23 patients (11 women, 12 men; mean age, 58 years). NIPP was routinely performed twice over a 4-week interval. Dose-limiting toxicities (DLTs) were defined using a 5 + 3 design, and cisplatin doses were escalated from 170 mg/m², with a fixed 5-fluorouracil dose of 1000 mg/m². The grade of adverse events (AEs) at the first and second sessions of NIPP therapy, pharmacokinetics, and antitumor response were evaluated. Results: No DLTs were observed during the first session of NIPP. However, at the second session, two patients experienced the DLT of neuropathy after administration of 200 mg/m² cisplatin. Therefore, 190 mg/m² cisplatin was indicated as the maximum tolerated dose (MTD). The plasma pelvic-to-systemic exposure ratio was 18.4 based on the maximum concentration and 19.0 based on the concentration-time curve. Solid tumor responses included complete response in two patients, partial response in five patients, stable disease in 15 patients, and progressive disease in one patient. Conclusion: NIPP may offer the safe delivery of high-dose regional chemotherapy (MTD of 190 mg/m² cisplatin) with negligible AEs and effective control of tumor growth in patients with incurable rectal cancer.

Background Orthograde percutaneous isolated hepatic perfusion (IHP) techniques using balloon occlusion catheters are relatively simple and facilitate repeated therapy, but they result in higher rates of leakage from the perfusion circuit into the systemic circulation. Therefore, a feasible protocol for percutaneous IHP with less leakage is required. Purpose To investigate hemodynamic changes in rat liver and tumor during retrograde-outflow isolated hepatic perfusion (R-IHP) with aspiration from the portal vein (PV). Material and Methods Animal experiments were approved by the Animal Experiment Ethics Committee of Lund University. Eighteen rats underwent R-IHP after laparotomy and catheterization of the PV and hepatic artery (HA). The HA, inferior vena cava (IVC), and PV were ligated, and flow through the suprahepatic IVC was controlled with a suture loop. The rats were divided into two groups to examine blood flow during R-IHP. Four rats (group 1) underwent arteriography via the HA with and without R-IHP, and 14 rats (group 2) were inoculated with tumor and examined by in vivo fluorescence microscopy of liver and tumor during R-IHP. Results In group 1, hepatic arteriography during R-IHP confirmed arterioportal communication in all four rats, with the PV acting as an outflow tract. In vivo fluorescence microscopy in group 2 showed strong enhancement of tumors, and no blood supply from the portal venules to the tumors was seen in any of the 14 rats. Blood flow in the major portion of the hepatic lobules was stopped and the percentage of enhanced area was significantly lower in the normal hepatic lobules than in the tumors (P < 0.0001). Conclusion We confirmed reversal of blood flow concomitant with good perfusion of the liver tumor and with reduced perfusion of normal liver parenchyma during R-IHP.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification system for the clinical management of patients with HCC and suggests that patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE). Interventional treatments such as TACE, balloon-occluded TACE, drug-eluting bead embolization, radioembolization, and combined therapies including TACE and radiofrequency ablation, continue to evolve, resulting in improved patient prognosis. However, patients with advanced-stage HCC typically receive only chemotherapy with sorafenib, a multi-kinase inhibitor, or palliative and conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. However, these patients require therapy that is more effective than sorafenib or conservative treatment. Several researchers try to perform more effective therapies, such as combined therapies (TACE with radiotherapy and sorafenib with TACE), modified TACE for HCC with arterioportal or arteriohepatic vein shunts, TACE based on hepatic hemodynamics, and isolated hepatic perfusion. This review summarizes the published data and data on important ongoing studies concerning interventional treatments for unresectable HCC and discusses the technical improvements in these interventions, particularly for advanced-stage HCC.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer‐related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation) can improve survival in HCC patients diagnosed at an early stage and offer potential long‐term curative effects. Patients with intermediate‐stage HCC benefit from transcatheter arterial chemoembolization (TACE), and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced‐stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced‐stage HCC.