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Introduction: To assess the efficacy of combined therapy involving bland transarterial embolization using gelatin sponge particles (bland GS-TAE) followed by transarterial chemoembolization using lipiodol mixed with anticancer agents and GS particles (Lip-TACE) to reduce the adverse events and increase the therapeutic effect of Lip-TACE in the treatment of huge (≥10 cm) hepatocellular carcinoma (HCC)., Material and Methods: Twenty-one consecutive patients with huge HCCs ( ≥ 10 cm in diameter) were enrolled in this study. First, bland GS-TAE was performed to reduce the tumor volume, and then Lip-TACE was performed to control the remaining tumor at intervals of around three weeks. Tumor response, survival, and adverse events of this combined therapy were assessed., Results: The tumor response was assessed three months after combined TACE, with complete response in 38.1% and partial response in 57.1% of cases. Severe adverse events were seen in two patients, acute cholecystitis and tumor rupture. The median survival time was 2.7 years, and the one-, two-, three-, and five-year overall survival rates were 76.2%, 66.7%, 42.9%, and 25.0%, respectively., Conclusion: Combined therapy involving bland GS-TAE followed by Lip-TACE can be performed safety and may improve survival in patients with huge HCCs.

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 C max 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.

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.

Background: Evidence of eribulin therapy for metastatic breast cancer (MBC) in clinical practice is not well documented., Methods: We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital., Results: The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m 2 , and 75%, respectively. One patient achieved a complete response, (CR) six a partial response (PR), eight stable disease (SD) and 14 patients exhibited progressive disease. The objective response rate (ORR: CR + PR) was 24.1%, and the clinical benefit rate (CBR: CR + PR + SD) was 51.7%. The median progression-free survival was 90 days (95% confidence interval [CI] 67-126) and median overall survival was 264 days (95% CI 198-357). In patients who previously received 2-4 regimens, the ORR was 28.5% and the CBR was 57.1%. In patients who received 5-12 regimens, the ORR was 20% and the CBR was 45%. Chemotherapy was administered to 20 patients (69%) after eribulin administration, and the median overall survival rate of cases that achieved greater than a PR was 1088 days. The most frequent treatment-related grade 3/4 adverse events were neutropenia (55.2%), and febrile neutropenia (20.1%). Grade 3 peripheral neuropathy occurred in 13.8% of patients, but was not exacerbated even if present before treatment., Conclusion: Eribulin is effective for MBC patients who have received multiple chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior therapy., (© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

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., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Outpatients undergoing chemotherapy receive oral anticancer drugs, supportive care medicine, and drugs for complications from health insurance pharmacies(ie, drugstores). Therefore, drugstore personnel and patients were surveyed using a questionnaire to ascertain the current conditions of information sharing between drugstores and hospitals. Only 31% of the patients surveyed responded that they received cancer chemotherapy via the drugstores, while a few of them understood the need for information sharing with the drugstore. We also found that the drugstores required a considerable amount of patient information including prescribed therapeutic drugs, treatment regimens, disease conditions, and test value. Therefore, we held a study session and clinical conference to facilitate the creation of an information-sharing system. In conclusion, it is imperative for drugstores and hospitals to cooperate and establish a strategy for information sharing in the future.

Objectives: To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma., Methods: Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression., Results: Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001)., Conclusion: Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma., Key Points: • Relative change in ADC value can predict survival in unresectable pancreatic cancer. • ADC change could determine a chemosensitivity of pancreatic cancer. • ADC values should be measured by excluding cystic, necrotic areas and vessels.

Hepatic arterial infusion chemotherapy (HAIC) combined with sorafenib is considered to be a promising therapeutic strategy for patients with advanced hepatocellular carcinoma. However, this combination therapy carries the risk of hepatic arterial thrombosis (HAT), which interrupts the continuation of HAIC, due to the side-effects of sorafenib. This case demonstrates a complication of HAT which occurred during HAIC combined with sorafenib. HAT was detected early by angiography via an implantable port-catheter system and was successfully treated with catheter-directed thrombolysis.

Purpose: To clarify the efficacy of transcatheter hepatic sub-subsegmental, subsegmental, and segmental arterial chemoembolization using lipiodol (subseg/seg lip-TACE) for hepatocellular carcinoma (HCC), long-term outcomes of patients who had been treated using subseg/seg lip-TACE alone were retrospectively examined., Materials and Methods: Subjects comprised 199 patients with HCC (T1/2/≥3=30/108/61; Child-Pugh A/B/C=115/52/32; Japan Integrated Staging [JIS] score≤1/2/≥3=88/64/47) who underwent subseg/seg lip-TACE using lipiodol mixed with an anticancer drug followed by injection of gelatin sponge particles. Each patient was followed-up every 3 months, and repeat subseg/seg lip-TACE and/or conventional lip-TACE was performed in cases showing recurrence. One-, 3-, 5-, 7-, and 10-year cumulative survival rates were calculated. Subgroup analyses were performed by stratifying the population according to T-factor, Child-Pugh classification, and JIS score., Results: Median duration of follow-up was 3.8 years (range 0.2 to 16.4). Median overall survival was 3.8 years. One-, 3-, 5-, 7- and 10-year survival rates were 91.5, 66.1, 38.8, 20.3, and 9.4% for all patients, and 95.5, 76.9, 51.9, 27.9 and 20.4% for patients with JIS≤1, respectively. Significant survival differences were found across two subgroups of staging systems (T2 vs. T3≤[P=0.0012] and JIS score≤1 vs. 2 [P=0.0036])., Conclusion: This study demonstrated that subseg/seg lip-TACE is a feasible treatment for obtaining prolonged survival in patients with localized HCC showing rich vasculature. Outcomes are influenced by both tumor stage and liver function, as seen in the best prolonged survival in patients with JIS score≤1.

A 69-year-old Japanese woman with multiple brain metastases secondary to non-small-cell lung cancer was treated with radiosurgery, and subsequently started oral gefitinib. Three years later, she presented with erythematous erosive alopecia with pustules on the scalp. A biopsy specimen showed a dense perifollicular infiltration composed of lymphocytes, neutrophils and abundant plasma cells. Methicillin-resistant Staphylococcus aureus was cultured from the lesions; however, treatment with antibiotics was not effective. We diagnosed an eruption resembling erosive pustular dermatosis of the scalp. Although oral steroids did not improve the lesions, the pustules and erythema of the scalp rapidly improved within a few weeks after discontinuation of gefitinib. There have been only 11 case reports of alopecia associated with epidermal growth factor receptor (EGFR) inhibitors including our case. It is noteworthy that all cases were female, and most cases involved the parietal scalp. Moreover, the reduction or discontinuation of the EGFR inhibitors was needed in all cases with erythematous alopecia, which remained as scarring alopecia., (Copyright © 2012 S. Karger AG, Basel.)

Background/purpose: It has been reported recently that adjuvant gemcitabine prolonged postoperative disease-free survival in patients with resectable pancreatic cancer. However, the efficacy was limited and further studies are required to improve the prognosis. In particular, postoperative hepatic recurrence often occurs even after gemcitabine treatment., Methods: We are currently trying to evaluate the efficacy of postoperative combination therapy of high-dose 5-fluorouracil (5-FU) arterial infusion with systemic gemcitabine. Patients received weekly high-dose 5-FU through the hepatic artery using a port-catheter system (1000 mg/m(2) for 5 h) plus concurrent systemic gemcitabine (1000 mg/m(2))., Results: Thirty-one patients were enrolled and 29 patients (94%) completed the scheduled adjuvant chemotherapy. The toxicity was acceptable and this regimen was well feasible as an outpatient treatment. At the time of analysis, 21 patients (68%) had recurrence. Local recurrence was most frequently observed, in 43% of the patients with recurrence. On the other hand, hepatic recurrence developed in only 2 patients (10%). The 1-year disease-free rate and overall survival rate were 62.9 and 100%, respectively., Conclusion: Our novel adjuvant strategy had a significant beneficial effect on early hepatic recurrence and may have the potential to prolong the overall survival of pancreatic cancer patients.

Objective: Arterial infusion chemotherapy for unresectable pancreatic cancer may be an attractive strategy. We are currently developing a new interventional radiology technique to unify the pancreatic blood supply for chemoinfusion. In this article, we evaluated the feasibility, therapeutic potential, and limitations of this technique., Materials and Methods: Twenty-eight patients with advanced pancreatic cancer were retrospectively reviewed. After the superior mesenteric artery was embolized, the drug distribution to the tumor was evaluated by a unified CT angiography system., Results: In all patients, tumors had dual arterial blood supplies from both the celiac and superior mesenteric arteries. Unification of pancreatic blood supply was successful in 14 patients (50%). The whole pancreatic tumor was exclusively supplied by the celiac artery in these patients. In the remaining 14 patients, a part of the tumor was still supplied by the superior mesenteric artery even after embolization. In most failed cases, the tumor had invaded to the root of the small-bowel mesentery or transverse mesocolon. By contrast, unification of the pancreatic blood supply could be achieved in cases invading to the stomach and duodenum. The whole liver was also successfully supplied by arterial infusion from the celiac artery after embolization., Conclusion: Our novel technique for arterial infusion chemotherapy is simple, feasible, and well tolerated. Furthermore, arterial chemoinfusion may be a breakthrough in selected patients with unresectable pancreatic cancer.

Purpose: To identify the drug infusion vessel for use in obtaining the best drug distribution in arterial infusion chemotherapy for advanced pancreatic cancer., Materials and Methods: In 16 cases of advanced pancreatic cancer (pancreatic head, n = 12; pancreatic body and/or tail, n = 4), computed tomography during arterial injection of contrast material was performed at the time of angiography. The sites of catheter placement were celiac artery, superior mesenteric artery, and their branches, such as gastroduodenal artery, inferior pancreatico-duodenal artery, or dorsal pancreatic artery., Results: In the cases of pancreatic head cancer, all except one with hepatomesenteric vascular variation were supplied by the celiac artery and superior mesenteric artery (dual supply). In the cases of pancreatic body and/or tail cancer, two were supplied by celiac artery alone and two showed dual supply. In the cases of pancreatic head cancer, when the areas supplied by the main trunk were compared with those supplied by its branches, three of nine cases on the celiac artery side and four cases on the superior mesenteric artery side showed that the areas were not consistent, with a partial defect observed in the areas supplied by branches of the superior mesenteric artery. In the cases of pancreatic body and/or tail cancer, on both sides, one of two cases was not consistent., Conclusions: To achieve optimal drug distribution in arterial infusion chemotherapy for advanced pancreatic cancer, drug infusion via both the celiac artery and superior mesenteric artery is required in the majority of cases. In many cases, optimal drug distribution is not attainable with drug infusion via a branch; therefore, drug infusion should be administered via the main trunk.

Simple Summary: Recently, favorable outcomes have been reported for hepatocellular carcinoma treated with transarterial chemoembolization (TACE) combined with lenvatinib (LEN-TACE). However, the optimal treatment protocol remains unclear. In this study, we performed a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE). The objective was to assess changes in tumor hemodynamics following the 4-day lenvatinib administration and to evaluate the outcomes of this combined therapy. A significant decrease in intra-tumor flow after lenvatinib was observed, with a 100% technical success rate and no severe adverse events. Complete response rates (CR) at 1 month were 75%, and the 12-month progression-free survival (PFS) rate was 75.0%. The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction radio by lenvatinib prior to TACE (r = −0.55). The short-term LEN-TACE is feasible and safe, demonstrating promising results, including a high CR rate and prolonged PFS. Aim: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. Methods: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4–12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. Results: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = −0.55). The 12-month progression-free survival (PFS) rate was 75.0%. Conclusions: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy. Methods: Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients ( n = 6). Complete response and complete protection were evaluated as secondary endpoints. Results: The accumulation ratios for C and AUC after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2 % [25/26]; CP rate, 92.3 % [24/26]). In the delayed phase (24-192 h post-chemotherapy), the complete response and complete protection rates were 76.9 % (20/26) and 61.5 % (16/26), respectively. Treatment was well tolerated. Conclusions: This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy. [ABSTRACT FROM AUTHOR]