Minimizing Systemic Leakage of Cisplatin during Percutaneous Isolated Pancreas Perfusion Chemotherapy: A Pilot Study.

PURPOSE: To evaluate the feasibility of percutaneous isolated pancreas perfusion (PIPP) by using a pig model. MATERIALS AND METHODS: All 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. RESULTS: Angiography and dye injection confirmed the patency of the PIPP system. Histopathologic examinations showed no abnormalities in the pancreas or other organs at a 40 mL/min infusion rate of cisplatin. However, edematous changes in the pancreas were observed at higher infusion rates. The pharmacologic effectiveness did not differ significantly among groups; therefore, the optimal infusion rate of 40 mL/min was selected. The median pancreatic-to-systemic exposure ratios were 71.8 for Cmax and 54.8 for the area under the curve. All laboratory data remained normal or returned to pretreatment levels within 1 week. CONCLUSION: PIPP at a 40 mL/min infusion rate appears to be safe and feasible for perfusion of the pancreas.

Retrograde-outflow percutaneous isolated hepatic perfusion using cisplatin: A pilot study on pharmacokinetics and feasibility.

OBJECTIVES: This study aimed to evaluate the feasibility and underlying pharmacokinetics of the retrograde-outflow technique for percutaneous isolated hepatic perfusion (PIHP). METHODS: 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. RESULTS: 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. CONCLUSIONS: The retrograde-outflow technique appears to enable safe and feasible PIHP therapy. KEY POINTS: • 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.

Pancreatic perfusion data and post-pancreaticoduodenectomy outcomes.

BACKGROUND: Precise risk assessment for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) may be facilitated using imaging modalities. Computed tomography perfusion (CTP) of the pancreas may represent histologic findings. This study aimed to evaluate the utility of CTP data for the risk of POPF after PD, in relation to histologic findings. METHODS: Twenty patients who underwent preoperative pancreatic CTP measurement using 320-detector row CT before PD were investigated. Clinicopathologic findings, including CTP data, were analyzed to assess the occurrence of POPF. In addition, the correlation between CTP data and histologic findings was evaluated. RESULTS: POPF occurred in 11 cases (grade A, 6; grade B, 5; and grade C, 0). In CTP data, both high arterial flow (AF) and short mean transit time (MTT) were related to POPF occurrence (P = 0.001, P = 0.001). AF was negatively correlated with fibrosis in the pancreatic parenchyma (r = -0.680), whereas MTT was positively correlated with fibrosis (r = 0.725). AF >80 mL/min/100 mL and MTT <16 s showed high sensitivity, specificity, positive predictive value, and negative predictive value (80.0%, 100.0%, 100.0%, and 83.3%, respectively) for the occurrence of POPF. CONCLUSIONS: CTP data for the pancreas were found to be correlated with the occurrence of POPF after PD. Alterations in the blood flow to the remnant pancreas may reflect histological changes, including fibrosis in the pancreatic stump, and influence the outcome after PD. CTP may thus facilitate objective and quantitative risk assessment of POPF after PD.

Evaluation of a near-infrared-type contrast medium extravasation detection system using a swine model.

PURPOSE: To refine the development and evaluate the near-infrared (NIR) extravasation detection system and its ability to detect extravasation during a contrast-enhanced computed tomography (CT) examination. MATERIALS AND METHODS: The NIR extravasation detection system projects the NIR light through the surface of the human skin then, using its sensory system, will monitor the changes in the amount of NIR that reflected, which varies based on absorption properties.Seven female pigs were used to evaluate the contrast media extravasation detection system, using a 20-gauge intravenous catheter, when injected at a rate of 1 mL/s into 4 different locations just under the skin in the thigh section. Using 3-dimensional CT images, we evaluated the extravasations between time and volume, depth and volume, and finally depth and time to detect. RESULTS: We confirmed that the NIR light, 950-nm wavelength, used by the extravasation detection system is well absorbed by contrast media, making changes easy to detect. The average time to detect an extravasation was 2.05 seconds at a depth of 2.0 mm below the skin with a volume of 1.3 mL, 2.57 seconds at a depth between 2.1 and 5 mm below the skin and a volume of 3.47 mL, 10.5 seconds for depths greater than 5.1 mm and a volume of 11.1 mL. The detection accuracy was significantly deteriorated when the depth exceeded 5.0 mm (Tukey-Kramer, P < 0.05) CONCLUSIONS: The extravasation system detection system that is using NIR has a high level of detection sensitivity. The sensitivity enables the system to detect extravasation at depths less than 2 mm with a volume of 1.5 mL and at depths less than 5 mm with a volume of 3.5 mL. The extravasation detection system could be suitable for use during examinations.

Strontium-89 (Sr-89) chloride in the treatment of various cancer patients with multiple bone metastases.

BACKGROUND: Although the use of Sr-89 chloride in the treatment of patients with prostate and breast cancer has been widely reported, little information is available about its use for other malignancies. Here, we retrospectively analyzed the clinical profile of Sr-89 chloride in various patients with painful bone metastases. METHODS: Entry criteria were a pathologically proven malignancy, clinically diagnosed multiple bone metastases, and adequate organ function. Sr-89 chloride (Metastron) was given by single intravenous infusion at 2 MBq/kg over 2 min. Self-reported outcome measures were used as a response index, including pain diary data on a 0-10 numeric rating scale (NRS). RESULTS: Fifty-four consecutive patients with painful bone metastases were treated with Sr-89 chloride at the National Cancer Center Hospital East between March 2009 and July 2011, consisting of 26 with breast/prostate cancer and 28 with other malignancies (lung 8, head and neck 6, colorectal 6, others 8). Thirteen (24 %) patients experienced a transient increase in pain, which was categorized as a flare-up response. Grade 3-4 anemia was observed in 6 patients, 3 of whom required blood transfusion. Regarding efficacy, response rates and complete response rates were 71.2 % and 34.6 %, respectively, and time to response from the initiation of treatment was 36 days (range, 13-217). No significant difference in response rates was seen between patients with breast/prostate cancer and other cancers (breast/prostate 69.2 %, other 73.1 %; p = 0.76). CONCLUSIONS: As in patients with breast and prostate cancer, Sr-89 chloride is a promising agent for the treatment of painful bone metastases in patients with various other malignancies.

Evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinoma with dual-energy CT.

PURPOSE: To evaluate the clinical usefulness of dual-energy computed tomography (CT) with weighted-average (WA) images and iodine overlay (IO) images in the evaluation of laryngeal cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma (SCC). MATERIALS AND METHODS: The institutional review board approved this retrospective study, and written comprehensive consent was obtained from all patients. Seventy-two consecutive patients underwent 128-section dual-source dual-energy CT to stage laryngeal (n=27) or hypopharyngeal (n=45) cancer. Three observers who were blinded to the patients' clinical histories and histopathologic findings evaluated cartilage invasion on WA images alone or in combination with IO images (nonossified cartilages were selectively evaluated on IO images) by using a five-point scale. Thirty of the 72 patients (42%) underwent surgery, and findings from histopathologic examination in those patients were used as the standard of reference for the evaluation of diagnostic performance with receiver operating characteristic (ROC) curve analysis and in terms of sensitivity and specificity. Interobserver reproducibility was calculated with κ statistics. RESULTS: For thyroid cartilage, the area under the ROC curve (AUC) of the WA plus IO images was marginally larger than that for WA images alone (AUC=0.957 vs 0.870, respectively; P=.075). The specificity of WA plus IO images was significantly superior to that of WA images alone (96% vs 70%, respectively; P=.031), with no compromise to the sensitivity (86% for both). For thyroid and cricoid cartilages, the interobserver reproducibility was higher for diagnoses made with WA plus IO images (κ=0.68-0.72 and 0.64-0.79, respectively) than for those made with WA images alone (κ=0.29-0.56 and 0.20-0.64, respectively). CONCLUSION: Combined analysis of WA and IO images obtained with dual-energy CT improves the diagnostic performance and interobserver reproducibility of evaluations of laryngeal cartilage invasion by SCC.

Phase I/II study of radiologic hepatic arterial infusion of fluorouracil plus systemic irinotecan for unresectable hepatic metastases from colorectal cancer: Japan Clinical Oncology Group Trial 0208-DI.

PURPOSE: Treatment of patients who have metastatic colorectal cancer (CRC) by using a combination of hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy has resulted in promising clinical outcomes. Additionally, image-guided HAIC is reported to be less invasive and distribute drugs more accurately than surgical HAIC. The purpose of this study was to assess the combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan in a multicenter phase I/II study. MATERIALS AND METHODS: Twenty-five patients with unresectable liver metastases from CRC were fitted with hepatic arterial catheter and port systems by using image-guided methods. Intraarterial fluorouracil (1,000 mg/m(2)) was administered on days 1, 8, and 15 of each treatment cycle. The dose of systemic irinotecan on days 1 and 15 was escalated from 75 mg/m(2). RESULTS: No dose-limiting toxicity was encountered during phase I, and the recommended dose of irinotecan was set at 150 mg/m(2). Grade 3 or higher adverse events included hyperglycemia (15%), elevated γ-glutamyl transpeptidase levels (15%), and neutropenia (9%). The response rate and median survival time were 72% and 49.8 months (95% CI, 27.5-78.1 mo), respectively. CONCLUSIONS: The combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan yielded favorable safety, response rate, and survival results. This combination should be evaluated in a large study.

Transcatheter arterial infusion chemotherapy with a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma refractory to transcatheter arterial chemoembolization.

OBJECTIVE: The aim of this study was to assess the safety and efficacy of transcatheter arterial infusion chemotherapy using a fine-powder formulation of cisplatin for patients with advanced hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. METHODS: We retrospectively examined the data of 84 consecutive patients with transcatheter arterial chemoembolization-refractory hepatocellular carcinoma who underwent transcatheter arterial infusion chemotherapy with a fine-powder formulation of cisplatin. Cisplatin was administered at the dose of 65 mg/m(2) into the feeding artery of the hepatocellular carcinoma. The treatment was repeated every 4-6 weeks, until the appearance of evidence of tumor progression or of unacceptable toxicity. RESULTS: Of the 84 patients, one patient (1.2%) showed complete response and two patients (2.4%) showed partial response, representing an overall response rate of 3.6% (95% confidence interval, 0.7-10.1). Of the remaining, 38 patients (45.2%) showed stable disease and 41 (48.8%) showed progressive disease. The median overall survival, 1-year survival rate and median progression-free survival in the entire subject population were 7.1 months, 27% and 1.7 months, respectively. Major Grade 3 or 4 adverse events included thrombocytopenia in 12 patients (14%) and elevation of the serum aspartate aminotransferase in 33 patients (39%). The gastrointestinal toxicities were mild and reversible. CONCLUSIONS: Transcatheter arterial infusion chemotherapy using a fine-powder formulation of cisplatin appears to have only modest activity, although the toxicity was also only mild, in patients with transcatheter arterial chemoembolization-refractory hepatocellular carcinoma.

Clinical value of whole-body FDG-PET for recurrent gastric cancer: a multicenter study.

OBJECTIVE: The purpose of this multicenter study was to evaluate the clinical usefulness of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) for suspected recurrent gastric cancer. METHODS: We performed a retrospective review of 92 consecutive patients who underwent PET [either integrated PET/computed tomography (CT) or manual fusion of dedicated PET and CT] scans for post-treatment surveillance of gastric cancer between June 2006 and December 2007. Of these patients, 46 patients were suspected of recurrence by other imaging modalities (Group A), 19 patients were suspected of recurrence by tumor markers without definite findings (Group B) and the remaining 27 patients underwent a PET scan without evidence of recurrence (Group C). The diagnostic performance and prevalence of the clinical impact of FDG-PET were analyzed. RESULTS: Recurrence of gastric cancer was confirmed in 31 patients (67%) in Group A, in 11 patients (58%) in Group B and in 2 patients (7%) in Group C. In addition, colon cancer (n = 3), lung cancer (n = 1) and pulmonary carcinoid (n = 1) were identified in five patients (5%). In patient-basis, the sensitivity, specificity and diagnostic accuracy of PET for recurrence were 81%, 87% and 83%, respectively, in Group A, 73%, 88% and 79%, respectively, in Group B and 50%, 88% and 85%, respectively, in Group C. Therapeutic management was influenced by PET results in 22 patients (48%) in Group A, in 8 patients (42%) in Group B and in 2 patients (7%) in Group C, including cases in which PET was helpful for detecting second primary cancer. CONCLUSIONS: PET with FDG yielded useful information in patients with suspected recurrent gastric cancer, especially when recurrence was suspected in the clinical setting.

Tubular gel fabrication and cell encapsulation in laminar flow stream formed by microfabricated nozzle array.

We have used a laminar flow stream formed by a microfabricated nozzle array to prepare cell-encapsulated alginate gel micro-tubes, in which cells formed a cylindrical multi-cellular aggregate after cultivation for two weeks.

Consistent liver metastases in a rat model by portal injection of microencapsulated cancer cells.

Consistent liver metastases in animal models is generally observed only with certain cancer cell lines. With the aim of improving on existing animal models of liver metastases, we hypothesized that cancer cells encased in 300 microm microcapsules, mimicking micrometastatic foci, might be effective seeds of liver metastases. A total of 3,000 microcapsules, containing 700 to 1,500 viable cells/capsule in logarithmic growth phase of three human pancreatic cancer cell lines (SUIT-2, AsPC-1, and BxPC-3), were transplanted in nude rats by portal injection. The rate of liver metastases was 100% (12 of 12), 100% (6 of 6), and 83% (5 of 6) for SUIT-2, AsPC-1, and BxPC-3 microcapsules, respectively. In contrast, the administration of an identical number of single cancer cells (2.1-4.5 x 10(6)) did not lead to liver metastases. Metastases was strictly limited to the liver, was quite stable, and could be proportionately tailored by varying the number of cancer microcapsules administered. Microscopic observation showed that two-thirds of the cancer microcapsules were lodged in the peripheral small (20-50 microm) portal veins, although one-third of the cancer microcapsules were trapped in the central wide (200-400 microm) portal vein. Capsules began to burst at day 3, with recognizable metastases produced at day 7, resulting in overt metastases production at days 28 to 42. The present cancer microcapsule method may be useful for obtaining liver metastases in animal models, especially for cell lines that will not form liver metastases with conventional single cell injection methods and/or for experiments requiring the consistent formation of liver metastases.

Evaluating the Feasibility of Isolated Pancreatic Perfusion for Chemotherapy Using Computed Tomography: An Experimental Study in Pig Models.

PURPOSE: Percutaneous isolated pancreatic perfusion (PIPP) is performed along with interventional radiology techniques to obtain high drug concentration by occluding the arterial inlet and venous outlet of the pancreas. The experimental study aimed to evaluate the contrast distribution in PIPP under different flow rates with or without anterior mesenteric artery (AMA) occlusion. MATERIALS AND METHODS: This study was approved by a local animal experiment ethics committee. Nine pigs were divided into Groups 1, 2, and 3, by infusion rates of 12, 24, and 36 mL/min. Groups 4 and 5 (3 pigs each) and Group 6 (2 pigs) underwent PIPP at the same respective infusion rates with and without AMA occlusion. Computed tomography (CT) arteriography was performed during PIPP with nonionic contrast media. The enhanced volume was calculated by adding the enhanced area in each slice using 1.25-mm axial images. The percent enhanced volume to the whole pancreas (%eV) was used to simulate drug distribution; the result was compared among groups. RESULTS: Without AMA occlusion, a larger %eV was obtained with high infusion rates (P = 0.039). The median %eV in Groups 1, 2, and 3 were 57.7, 74.2, and 90.5%, respectively. With AMA occlusion, CT demonstrated duodenal enhancement at an infusion rate of 36 mL/min, and the median %eV in Groups 4, 5, and 6 were 92.8, 95.4, and 98.5%, respectively. A significantly larger %eV was obtained after AMA occlusion (P = 0.031). CONCLUSION: A higher infusion rate or AMA occlusion increases the enhanced volume in PIPP in pig models. LEVEL OF EVIDENCE: No level of evidence.

Size control of calcium alginate beads containing living cells using micro-nozzle array.

Size-controlled small (i.e. less than 300 microm) polyelectrolyte complex gel beads are urgently desired for wide-spread application, including use in medical, pharmaceutical, and bioengineering fields. However, it was impossible to obtain smaller beads less than 300 microm with conventional apparatuses. We developed a novel microfluidics device that utilizes silicon micro-nozzle (MN) array, enabling to produce 50-200 microm calcium alginate beads with a narrow size distribution. Alginate aqueous solution was extruded through a precisely fabricated thin (30 microm x 30 microm) and short (500 microm) MN and was sheared by the viscous drag force of oil flow to form alginate droplets. Alginate droplets were immediately reacted with CaCl2 droplets at the downstream of oil flow to form calcium alginate gel beads. This device enabled us to successfully encapsulate living cells into 162 microm calcium alginate beads with maintaining viability, which was confirmed by the expression of marker protein.

Reduction of drug leakage by negative-balance isolated pelvic perfusion: correlation between leakage and in-out flow rate in a pig model.

PURPOSE: Isolated pelvic perfusion (IPP) therapy exposes target tissues to high doses of anticancer drugs with low systemic concentrations, but the major drawback is drug leakage into the systemic circulation, which often thwarts the increased drug concentration. In this study, the efficacy of altering the in-out flow rate during IPP in order to decrease the leakage was assessed in adult pigs. METHODS: The abdominal aorta and the infrarenal vena cava were occluded with two balloon catheters, blood in the extracorporeal circuit was circulated with twin rotary pumps, and the IPP was performed with platinum. Three sets of in-out flow rates were used, and the degree of drug leakage into the systemic circulation was evaluated. The volume of blood withdrawn was equal to the volume returned (300 ml/min; group A), 5% higher (group B), or 10% higher (group C). The platinum concentrations in the pelvic circulation, systemic circulation, and urine were measured and compared. RESULTS: The average and maximum plasma platinum concentrations in the pelvic circulation did not significantly differ among the three groups. The plasma platinum concentrations in the systemic venous circulation of the three groups significantly (P<0.01) decreased as the volume withdrawn during IPP increased. The percentage of platinum eliminated in the urine during IPP was significantly (P<0.01) lower in group B and C than in group A. CONCLUSIONS: Setting the volume withdrawn higher than the volume returned decreased leakage into the systemic circulation under isolated pelvic perfusion.

Pulmonary involvement of malignant melanoma: thin-section CT findings with pathologic correlation.

OBJECTIVES: The purpose of this study was to characterize the thin-section computed tomography (CT) findings of primary and secondary pulmonary malignant melanoma and to correlate them with the histopathologic features. MATERIALS AND METHODS: Patients were identified from a pathologic registration system database through a query for patients with diagnosed primary or secondary pulmonary melanoma who had undergone surgical resection. A total of 19 pulmonary malignant melanomas, including one primary and 18 secondary involvements, from 10 patients were enrolled into this study. The patients consisted of 3 men and 6 women, with a mean age of 55 years (range, 28 to 71 years). Thin-section CT findings evaluated by consensus between two radiologists were compared with the histopathologic specimens. RESULTS: Tumor size ranged from 4 to 62 mm (mean, 19 mm) on thin-section CT images. Four characteristic patterns including solitary or multiple solid nodule, endobronchial lesion, cavitary nodule, and nodule with ground-glass attenuation were disclosed by correlation between thin-section CT and pathologic findings. The most common thin-section CT finding was a solid nodule with a well-defined, smooth margin (n=14). Endobronchial lesions were seen in one primary and one secondary involvement (n=2). Less common CT findings were cavitary nodule (n=1) and nodule with ground-glass attenuation (n=1). CONCLUSION: Primary and secondary pulmonary malignant melanomas show various patterns of involvement on thin-section CT.

Pulmonary lymphangioleiomyomatosis in a male patient with tuberous sclerosis complex.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease of unknown etiology that occurs almost exclusively in women of reproductive age. High-resolution computed tomography (HRCT) reveals the striking feature of diffuse cystic changes throughout the lung parenchyma. The correct diagnosis may be delayed by several years after the onset of symptoms because of the rarity of the disease and the need for chest CT scans to identify the lung involvement. We describe a case of pulmonary LAM in a male patient associated with tuberous sclerosis complex (TSC), in whom the early stage of disease could be depicted by chest HRCT scans.

Hepatic hemangioma presenting atypical radiologic findings: a case report.

A 69-year-old woman was referred to our hospital due to a liver tumor that was incidentally noted on ultrasound (US). US revealed a pedunculated mass of 5 cm in diameter, with a heterogeneous echo pattern. On arterial phase dynamic contrast-enhanced computed tomography (CT), a tiny enhancing dot in the upper aspect of the mass was seen; whereas, the main portion of the lesion appeared as hypoattenuating. The tumor was of low intensity on T1-weighted magnetic resonance (MR) images, and showed slightly heterogeneous high intensity on T2-weighted MR images. The most characteristic feature of the tumor was its exophytic appearance. On post-gadolinium hepatic arterial dominant-phase MR images, the tumor showed nodular enhancement centrally, with progressive spread of enhancement on later images. Angiography showed dilatation of the right posterior inferior branch of the hepatic artery and C-shaped opacification. Since we could not rule out malignancy for these nonspecific radiologic findings, a partial resection of the liver was carried out, resulting in a pathological diagnosis of hepatic hemangioma. This hemangioma had marked hyalinization and fibrosis, causing a heterogeneous appearance on MR images. The tumor presented an exophytic appearance, which caused some diagnostic confusion.

Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus.

Transcatheter arterial chemoembolization (TACE) is used in the treatment of hepatocellular carcinoma; however, it has limited effect on portal vein tumor thrombus (PVTT). The purpose of this study was to assess the feasibility and efficacy of radiotherapy targeting the PVTT after TACE for the tumor in the hepatic parenchyma. TACE was performed using epirubicin hydrochloride, iodized poppy seed oil, and gelatin sponge particles. Radiotherapy was performed targeting the PVTT to a total dose of 50 Gy in 25 fractions during 5 weeks. Twenty consecutive patients were treated with this combined treatment. Sixteen of 20 patients could complete the planned radiotherapy. Partial response was observed in 10, no change in 4, and progression in 6. The response rate was 50% (95% CI 28-72%). The 1-year overall survival rate was 25% (95% CI 6-44%), and the median survival time was 5.3 months. It was difficult to determine the late toxicities because of disease progression and additional TACE, and only one patient died without disease progression. Radiotherapy after TACE is feasible for patients with hepatocellular carcinoma and PVTT. The survival figure, however, is still dismal, and further investigation is needed to establish the best combination of treatment modalities.

Pilot study of transcatheter arterial chemoembolization with degradable starch microspheres in patients with hepatocellular carcinoma.

We prospectively evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) with microembolization material, degradable starch microspheres (DSMs), and epirubicin, for treatment of multifocal hepatocellular carcinoma (HCC). Seventeen patients with multifocal HCC were treated. At the first treatment, DSMs were injected alone to determine the dose for embolization of the hepatic artery in each patient. After 4 weeks, TACE was performed every 4 to 6 weeks with a mixture of DSMs and epirubicin at a dose of 40 mg/m2. A necrotic area of more than 50% was produced in 6 patients by DSMs alone, and in 11 patients by TACE. The overall response rate was 52.9% (2 complete and 7 partial responses). The duration of the responses ranged from 4 to 21 months (median: 9 months). Common toxicities were transient abdominal pain, nausea/vomiting, fever, and leukopenia. In four patients, grade III or IV toxicity was observed as gamma-glutamyl transpeptidase elevation. TACE with DSMs had tumor necrosis efficacy with acceptable toxicity. The median survival time was 21.7 months, and the 2-year survival rate was 45.3%. Further investigation of the effects of DSM treatment on survival should be carried out.

Effect of interfacial tension on the dynamic behavior of droplet formation during microchannel emulsification.

Microchannel (MC) emulsification is a novel technique for producing monodisperse emulsions. In this study, we investigated the effect of interfacial tension on the dynamic behavior of droplet formation with various surfactant concentrations. Interfacial tension did not affect the resultant droplet diameter in lower flow velocity ranges, but it did affect the time-scale parameters. These results were interpreted using the droplet formation mechanism reported in our previous study. At surfactant concentrations below 0.3%, the emulsification behavior was differed from that at higher surfactant concentrations. An analysis of diffusional transfer indicated that dynamic interfacial tension affects the emulsification behavior at lower surfactant concentrations. Dynamic interfacial tension that exceeded the equilibrium value led to a shorter detachment time. This resulted in stable droplet formation of monodispersed emulsions by spontaneous transformation, even at flow velocities above the predicted critical flow velocity. A previous study predicted that the droplet formation would become unstable and polydispersed larger droplets would form over critical flow velocity. Wetting of the MC with the dispersed phase at lower surfactant concentrations induced formation of larger polydispersed droplets at high flow velocities.