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.

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.

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.

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.

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.

Primary staging of laryngeal and hypopharyngeal cancer: CT, MR imaging and dual-energy CT.

Laryngeal and hypopharyngeal cancer, in particular T4a disease associated with cartilage invasion and extralaryngeal spread, needs to be evaluated accurately because treatment can impact heavily on a patient's quality of life. Reliable imaging tools are therefore indispensible. CT offers high spatial and temporal resolution and remains the preferred imaging modality. Although cartilage invasion can be diagnosed with acceptable accuracy by applying defined criteria for combinations of erosion, lysis and transmural extralaryngeal spread, iodine-enhanced tumors and non-ossified cartilage are sometimes difficult to distinguish. MR offers high contrast resolution for images without motion artifacts, although inflammatory changes in cartilage sometimes resemble cartilage invasion. With dual-energy CT, combined iodine overlay images and weighted average images can be used for evaluation of cartilage invasion, since iodine enhancement is evident in tumor tissue but not in cartilage. Extralaryngeal spread can be evaluated from CT, MR or dual-energy CT images and the routes of tumor spread into the extralaryngeal soft tissue must be considered; (1) via the thyrohyoid membrane along the superior laryngeal neurovascular bundle, (2) via the inferior pharyngeal constrictor muscle, and (3) via the cricothyroid membrane. Radiologists need to understand the advantages and limitations of each imaging modality for staging of laryngeal and hypopharyngeal cancer.

Efficacy of sorafenib in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization.

BACKGROUND: The efficacy of sorafenib for hepatocellular carcinoma (HCC) patients refractory to transcatheter arterial chemoembolization (TACE) has not yet been clarified. We investigated the efficacy of sorafenib in HCC patients who were refractory to TACE (sorafenib group) and retrospectively compared the results with those of patients treated with hepatic arterial infusion chemotherapy using cisplatin (cisplatin group). METHODS: We evaluated the anti-tumor effect, the time to progression, and the overall survival in 48 patients in the sorafenib group and 66 patients in the cisplatin group. RESULTS: The disease control rate to sorafenib was 60.4 %, the median time to progression was 3.9 months, and the median survival time was 16.4 months in patients who were refractory to TACE. When compared with the cisplatin group, significant differences in the patient characteristics were not observed between the two groups with the exception of patient age; however, the disease control rate (cisplatin group 28.8 %, P = 0.001), time to progression (cisplatin group: median 2.0 months, hazard ratio 0.44, P < 0.01), and overall survival (cisplatin group: median 8.6 months, hazard ratio 0.57, P < 0.001) were significantly superior in the sorafenib group. The multivariate analysis also showed the sorafenib treatment to be the most significant factor contributing to prolongation of time to progression and overall survival. CONCLUSIONS: Sorafenib showed favorable treatment results in patients refractory to TACE. When compared with hepatic arterial infusion chemotherapy using cisplatin, sorafenib demonstrated a significantly higher disease control rate, a longer time to progression and increased overall survival.

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.

Blood vessel-based liver segmentation using the portal phase of an abdominal CT dataset.

PURPOSE: Blood vessel (BV) information can be used to guide body organ segmentation on computed tomography (CT) imaging. The proposed method uses abdominal BVs (ABVs) to segment the liver through the portal phase of an abdominal CT dataset. This method aims to address the wide variability in liver shape and size, separate liver from other organs of similar intensity, and segment hepatic low-intensity tumors (LITs). METHODS: Thin ABVs are enhanced using three-dimensional (3D) opening. ABVs are extracted and classified into hepatic BVs (HBVs) and nonhepatic BVs (non-HBVs) with a small number of interactions, and HBVs and non-HBVs are used for constraining automatic liver segmentation. HBVs are used to individually segment the core region of the liver. To separate the liver from other organs, this core region and non-HBVs are used to construct an initial 3D boundary surface. To segment LITs, the core region is classified into non-LIT- and LIT-parts by fitting the histogram of the core region using a variational Bayesian Gaussian mixture model. Each part of the core region is extended based on its corresponding component of the mixture, and extension is completed when it reaches a variation in intensity or the constructed boundary surface, which is reconfirmed to fit robustly between the liver and neighboring organs of similar intensity. A solid-angle technique is used to refine main BVs at the entrances to the inferior vena cava and the portal vein. RESULTS: The proposed method was applied to 80 datasets: 30 Medical Image Computing and Computer Assisted Intervention (MICCAI) and 50 non-MICCAI; 30 datasets of non-MICCAI data include tumors. Our results for MICCAI-test data were evaluated by sliver07 (http://www.sliver07.org/) organizers with an overall score of 85.7, which ranks best on the site as of July 2013. These results (average ± standard deviation) include the five error measures of the 2007 MICCAI workshop for liver segmentation as follows. Results for volume overlap error, relative volume difference, average symmetric surface distance, root mean square symmetric surface distance, and maximum symmetric surface distance were 4.33 ± 0.73, 0.28 ± 0.87, 0.63 ± 0.16, 1.19 ± 0.28, and 14.01 ± 2.88, respectively; and when applying our method to non-MICCAI data, results were 3.21 ± 0.75, 0.06 ± 1.29, 0.45 ± 0.17, 0.98 ± 0.26, and 12.69 ± 3.89, respectively. These results demonstrate high performance of the method when applied to different CT datasets. CONCLUSIONS: BVs can be used to address the wide variability in liver shape and size, as BVs provide unique details for the structure of each studied liver. Constructing a boundary surface using HBVs and non-HBVs can separate liver from its neighboring organs of similar intensity. By fitting the histogram of the core region using a variational Bayesian Gaussian mixture model, LITs are segmented and measuring the volumetry of non-LIT- and LIT-parts becomes possible. Further examination of the proposed method on a large number of datasets is required for clinical applications, and development of the method for full automation may be possible and useful in the clinic.

A multi-institutional phase II trial of hepatic arterial infusion chemotherapy with cisplatin for advanced hepatocellular carcinoma with portal vein tumor thrombosis.

PURPOSE: The objective of this study was to evaluate the response rate, survival, and adverse effects of hepatic arterial infusion chemotherapy (HAIC) using cisplatin in patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHODS: Twenty-five patients of advanced HCC with PVTT in the main or first branch, having no prior history of chemotherapy, measurable lesions, adequate liver and renal function, and adequate bone marrow reserve, were enrolled. Cisplatin was administered at the dose of 65 mg/m(2) via the proper hepatic artery. Treatment was repeated every 4-6 weeks for a maximum of six courses until the appearance of evidence of tumor progression or unacceptable toxicity. RESULTS: The median number of treatments was 3 (range 1-6). Among the 25 enrolled patients, complete response was achieved in 1 (4 %) patient and partial response in 6 (24 %), corresponding to a response rate of 28 % (95 % CI 12-49 %). The median progression-free and overall survival times and the 1-, 2-, and 3-year survival rates in the enrolled patients were 3.6 and 7.6 months and 40.3, 36.0, 20 %, respectively. Four of the seven patients who showed complete or partial response survived for more than 3 years. The main grade 3/4 non-hematological adverse events of this treatment were elevation of the serum aspartate aminotransferase (44 %) and alanine aminotransferase (24 %). CONCLUSION: HAIC with cisplatin exerts moderate activity with mild toxicity in advanced HCC patients with PVTT. Especially, markedly prolonged survival can be expected in patients who respond to this treatment.

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.

Transarterial chemoembolization using cisplatin powder in a rabbit model of liver cancer.

The purpose of this study was to investigate the pharmacological advantages of transarterial chemoembolization (TACE) with cisplatin powder for hypervascular hepatic tumors in animal experiments. VX2 tumors were transplanted to the livers of nine rabbits. Cisplatin (1 mg/kg) was infused into the proper hepatic artery. In the cisplatin-HAI group, cisplatin solution was infused. In the cisplatin-GS-TACE group, after infusion of cisplatin solution, gelatin sponge particles were used for embolization. In the cisplatin-Lp-TACE group, after infusion of a cisplatin powder and lipiodol (10 mg/ml) suspension, gelatin sponge particles were used for embolization. Before and after administration, platinum concentrations in plasma were measured. Using liver specimens that were excised 60 min after infusion, platinum concentrations in tumorous and nontumorous liver tissues were measured. The mean platinum concentration in tumorous tissue was 0.88 microg/ml for the cisplatin-HAI group, 1.23 microg/ml for the cisplatin-GS-TACE group, and 12.65 microg/ml for the cisplatin-Lp-TACE group. The platinum concentration for the cisplatin-Lp-TACE group was significantly higher than that for the cisplatin-HAI group (p = 0.004) and the cisplatin-GS-TAE group (p = 0.004). The mean platinum concentration in nontumorous liver tissue was 0.98 microg/ml for the cisplatin-HAI group, 1.13 microg/ml for the cisplatin-GS-TACE group, and 1.09 microg/ml for the cisplatin-Lp-TACE group; no significant differences were seen. At both 5 and 10 min after infusion, the platinum concentrations for the cisplatin-Lp-TACE group were lower than those for the other two groups. The present results suggest that TACE using cisplatin powder/lipiodol suspension and gelatin sponge for hypervascular hepatic tumors has a number of pharmacological advantages.

Microfabricated airflow nozzle for microencapsulation of living cells into 150 micrometer microcapsules.

Microencapsulation of genetically engineered cells has attracted much attention as an alternative nonviral strategy to gene therapy. Though smaller microcapsules (i.e. less than 300 microm) theoretically have various advantages, technical limitations made it difficult to prove this notion. We have developed a novel microfabricated device, namely a micro-airflow-nozzle (MAN), to produce 100 to 300 microm alginate microcapsules with a narrow size distribution. The MAN is composed of a nozzle with a 60 microm internal diameter for an alginate solution channel and airflow channels next to the nozzle. An alginate solution extruded through the nozzle was sheared by the airflow. The resulting alginate droplets fell directly into a CaCl2 solution, and calcium alginate beads were formed. The device enabled us to successfully encapsulate living cells into 150 microm microcapsules, as well as control microcapsule size by simply changing the airflow rate. The encapsulated cells had a higher growth rate and greater secretion activity of marker protein in 150 microm microcapsules compared to larger microcapsules prepared by conventional methods because of their high diffusion efficiency and effective scaffold surface area. The advantages of smaller microcapsules offer new prospects for the advancement of microencapsulation technology.

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.

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.

Incidence of multiple primary malignancies in a cohort of adult patients with soft tissue sarcoma.

OBJECTIVE: Some studies to date have suggested the development of multiple primary malignancies in patients with soft tissue sarcoma. The current study was performed to quantify the risk of development of multiple primary malignancies in adult patients with soft tissue sarcoma. METHODS: A total of 406 consecutive patients who were diagnosed with soft tissue sarcoma were identified in the study analysis. The cumulative incidence of multiple malignancies was calculated by comparing Kaplan-Meier curves and log-rank tests from each histological type. A Cox proportional hazards model was used to estimate the influence on the hazard ratio (HR) of each variable. RESULTS: A total of 35 patients with soft tissue sarcoma (9%), having preceding (n = 15) and subsequent (n = 20) malignancies other than soft tissue sarcoma were documented. The 5- and 10-year estimated cumulative incidence of multiple primary malignancies were 7.6 and 12.3%, respectively. The hazard risk of multiple primary malignancies adjusted for potential confounding variables was significantly associated with age at diagnosis (HR = 1.51, P = 0.0019). The risk of multiple primary malignancies was also increased in patients with myxofibrosarcoma adjusted by the potential confounding variables (HR = 2.34, P = 0.048). The 5- and 10-year estimated cumulative incidence of multiple primary malignancies in patients with myxofibrosarcoma were both 16.9%. CONCLUSION: The results of our study confirm that the risk of multiple malignancies appears to be impacted by age at the time of diagnosis of the first tumor and by the histological type of myxofibrosarcoma.