Achievements and challenges of the Sakigake designation system in Japan.

The Sakigake designation system (Sakigake) has been launched to encourage the pioneered development of innovative new medical products for the effective treatment of severe illness in Japan, which allows leveraging the several advantages in prioritized consultation, rapid review, premium drug pricing and extended data-protection period. We retrospectively analysed the Sakigake products including drugs and regenerative medical products to clarify the achievements and the future issues in this system. From April 2015 to August 2020 (the first 5-year trial period of Sakigake), 37 products were designated, and 10 of those were approved in Japan in which 7 new active substances achieved the first-in-world approvals. Oncology, neurology and cardiovascular disease were the major therapeutic areas, and those 3 accounted for 75.7% of all products. Sakigake achieved some first-in-world approvals by the Pharmaceuticals and Medical Devices Agency/the Ministry of Health, Labor and Welfare of innovative new medical products, although in some therapeutic areas, there remains room in stimulating drug development.

Rationales of delay and difference in regulatory review by Japan, the USA and Europe among new drugs first approved in Japan.

AIMS: To clarify the rationales of delay or difference in the review of new drug applications among regulatory authorities for new drugs, those first approved in the world being in Japan. METHODS: Among 80 new drugs first approved in Japan from 2008 to 2019, we identified those subsequently approved in the USA or Europe. Significant delays in approval time (boxplot outliers) and the rationales for the delays were assessed among the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). RESULTS: Of the 80 Japan-first approvals, 25 and 24 were approved in the USA and Europe, respectively, and their median approval times in Japan, the USA and Europe were 285, 334 and 477 days, respectively. Significant delays were identified for pirfenidone (1806 days, FDA), alogliptin benzoate (1856 days, FDA), insulin degludec (1457 days, FDA) and romosozumab (750 days, PMDA; 994 days, FDA; 748 days, EMA). Due to concerns about cardiovascular risk, alogliptin benzoate and insulin degludec were requested for additional clinical trials by the FDA, and romosozumab required a much longer review period than the standard approval time in all three regions. CONCLUSIONS: Among the new drugs significantly delayed in approval time in Japan, the USA or Europe, there were some differences in the requirements, the participating regions and the assessment of clinical trials. The regulatory views on the cardiovascular risk also differed among the three regions. These divergences may be associated with the differences in approval histories.

Manipulable Metal Catalyst for Nanographene Synthesis.

Performing bottom-up synthesis by using molecules adsorbed on a surface is an effective method to yield functional polycyclic aromatic hydrocarbons (PAHs) and nanocarbon materials. The intramolecular cyclodehydrogenation of hydrocarbons is a critical process in this synthesis; however, thus far, its elementary steps have not been elucidated thoroughly. In this study, we utilize the metal tip of a low-temperature noncontact atomic force microscope as a manipulable metal surface to locally activate dehydrogenation for PAH-forming cyclodehydrogenation. This method leads to the dissociation of a H atom of an intermediate to yield the cyclodehydrogenated product in a target-selective and reproducible manner. We demonstrate the metal-tip-catalyzed dehydrogenation for both benzenoid and nonbenzonoid PAHs, suggesting its universal applicability as a catalyst for nanographene synthesis.

Efficacy of combined bland embolization and chemoembolization for huge (≥10 cm) hepatocellular carcinoma.

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.

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

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

Electrostatic Repulsion-Induced Desorption of Dendritic Viologen-Arranged Molecules Anchored on a Gold Surface through a Gold-Thiolate Bond Leading to a Tunable Molecular Template.

We investigated the adsorption and desorption behavior of self-assembled monolayers (SAMs) on gold derived from dendritic viologen-arranged molecules with an ω-mercaptodecyl group (A n, n (dendritic generation) = 0-3) at the apex of the dendritic structure in polar solvents. The adsorption of the dendritic molecules occurred quickly and saturated within a few minutes in an acetonitrile/ethanol (1/1, v/v) mixture at a concentration of 2 mM. Atomic force microscopy images of the SAMs showed flat surfaces regardless of the dendritic generation because the peripheral viologen units were closely packed at the surface of the molecular layer. Individual A3 molecules immobilized on the substrate were observed by scanning tunneling microscopy measurements of a mixed SAM with decanethiol. The desorption behaviors of dendritic molecules from the A n-SAMs in several solvents such as water were also investigated. The spontaneous desorption of the A n-SAM occurred more rapidly than that of a conventional n-alkanethiol SAM. However, the desorption was inhibited by adding electrolytes such as NaNO3 due to the shielding effect on the electrostatic repulsion between the dendritic molecules. These results indicate that the surface density of the dendritic molecules can be controlled through the desorption.

Orientation and Electronic Structures of Multilayered Graphene Nanoribbons Produced by Two-Zone Chemical Vapor Deposition.

The orientation and electronic structure of multilayered graphene nanoribbons with an armchair-edge (AGNRs) were determined by low-temperature scanning tunneling microscopy in this study. The orientation of AGNRs was found to be an edge-on structure when positioned as a top layer, while previous reports showed a face-on structure for monolayered AGNRs on Au(111). According to density functional theory calculations, AGNRs in a top layer preferentially form as edge-on structures rather than face-on structures due to the balance of CH-π and π-π interactions between AGNRs. Scanning tunneling spectroscopy and density functional theory calculations revealed that the electronic structures of multilayered AGNRs are similar to those in a gas-phase due to the lack of interaction between AGNRs and the Au(111) substrate. The observation of AGNRs in mutilayers might suggest the conformation-assisted mechanism of dehydrogenation when there is no contact with the Au(111) substrate.

Clinical features and treatment outcomes of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV): A retrospective analysis of 235 patients from a nationwide survey in Japan.

OBJECTIVE: We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV). METHODS: This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text. RESULTS: Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and older (median age: 68 years); (3) predominantly myeloperoxidase (MPO)-ANCA-positive (60%), followed by proteinase 3 (PR3)-ANCA-positive (19%) and both ANCAs-negative (16%); (4) frequently observed accompanying facial palsy (36%) and hypertrophic pachymeningitis (28%); and (5) disease often involving lung (35%) and kidney (26%) lesions. Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse. The occurrence of hypertrophic pachymeningitis was associated with facial palsy (p < 0.05), both ANCAs-negative phenotype (p < 0.001), and headache (p < 0.001). The administration of corticosteroid together with an immunosuppressant was an independent predicting factor for lack of disease relapse (odds ratio [OR] = 1.90, p = 0.03) and an improvement in hearing loss (OR =2.58, p = 0.0002). CONCLUSION: Since OMAAV has novel clinical features, the disease may be categorized as a subentity for the classification of AAV.

Switch of the magnetic field effect on photon upconversion based on sensitized triplet-triplet annihilation.

Magnetic field effects (MFEs) on photon upconversion based on sensitized triplet-triplet annihilation (TTA-UC) are examined in platinum(ii) octaethylporphyrin/9,10-diphenylanthracene (DPA) systems at different DPA concentrations and laser power densities. Positive MFEs on TTA-UC are observed for the first time and are most likely attributable to aggregation of DPA.

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

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

Simple technique for gasless transumbilical single-incisional laparoscopic-assisted appendectomy.

PURPOSE: Single-incision laparoscopic surgery has recently received more attention. We developed a novel simple technique of gasless transumbilical single-incisional laparoscopic-assisted appendectomy (TUSILAA) and retrospectively analyzed our initial experience. METHODS: TUSILAA has been attempted in 50 consecutive patients with acute appendicitis. The vertical incision through the umbilicus was used for laparoscopic access and the abdominal wall was lifted by a Kent retractor set system. RESULTS: Our technique was successful in 45 out of 50 (90 %) patients. The median operating time was 59 min (range 35-140). The median length of postoperative hospital stay was 4 days (range 2-12). None of the cases were converted to open appendectomy. There were no perioperative surgical complications. CONCLUSIONS: Our novel technique, gasless TUSILAA, is safe and feasible with acceptable operative time and excellent cosmetic result. Furthermore, this procedure has the advantage of cost-effectiveness since any disposable instruments including trocars, staplers, or expensive devices are not required. Therefore, this could be used as the first-choice surgical procedure for selected patients with uncomplicated acute appendicitis.

On-Surface Fabrication toward Polar 2D Macromolecular Crystals.

Polar 2D macromolecular structures have attracted significant attention because of their ferroelectricity and ferro-magnetism. However, it is challenging to synthesize them experimentally because dipoles or spins of these macromolecules tend to cancel each other. So far, there has been no successful strategy for assembling macromolecules in a unidirectional manner, achieving stereoregular polymerization on metal surfaces, and creating polar 2D polymer crystals. Recent progress in molecular assembly, on-surface polymer synthesis, and direct control of molecules using electric field applications provides an opportunity to develop such strategies. In this regard, we first review past studies on chiral and achiral molecular assembly, on-surface polymer synthesis, and orientation control of polar molecules. Then, we discuss our newly developed approach called "vectorial on-surface synthesis", which is based on "dynamic chirality" of compass precursors, stereoselective polymerization, and favorable interchain interactions originating from CH-π interactions. Finally, we conclude with a prospective outlook.

Platinum Nanoparticles Bonded with Carbon Nanotubes for High-Performance Ampere-Level All-Water Splitting.

Platinum nanoparticles loaded on a nitrogen-doped carbon nanotubes exhibit a brilliant hydrogen evolution reaction (HER) in an alkaline solution, but their bifunctional hydrogen and oxygen evolution reaction (OER) has not been reported due to the lack of a strong Pt-C bond. In this work, platinum nanoparticles bonded in carbon nanotubes (Pt-NPs-bonded@CNT) with strong Pt-C bonds are designed toward ultralow overpotential water splitting ability in alkaline solution. Benefit from the strong interaction between platinum and high conductivity carbon nanotube substrates through the Pt-C bond also the platinum nanoparticles bonded in carbon nanotube can provide more stable active sites, as a result, the Pt-NPs-bonded@CNT exhibits excellent hydrogen evolution in acid and alkaline solution with ultralow overpotential of 0.19 and 0.23 V to reach 1000 mA cm-2, respectively. Besides, it shows superior oxygen evolution electrocatalysis in alkaline solution with a low overpotential of 1.69 V at 1000 mA cm-2. Furthermore, it also exhibits high stability over 110 h against the evolution of oxygen and hydrogen at 1000 mA cm-2. This strategy paves the way to the high performance of bifunctional electrocatalytic reaction with extraordinary stability originating from optimized electron density of metal active sites due to strong metal-substrate interaction.

Surface-Modified Ruthenium Nanorods for an Ampere-Level Bifunctional Hydrogen Evolution Reaction/Oxygen Evolution Reaction Electrocatalyst.

The practical applications of bifunctional ruthenium-based electrocatalysts with two active sites of Ru nanoparticles covered with RuO2 skins are limited. One reason is the presence of multiple equally distributed facets, some of which are inactive. In contrast, ruthenium nanorods with a high aspect ratio have multiple unequally distributed facets containing the dominance of active faces for efficient electrocatalysis. However, the synthesis of ruthenium nanorods has not been achieved due to difficulties in controlling the growth. Additionally, it is known that the adsorption capacity of intermediates can be impacted by the surface of the catalyst. Inspired by these backgrounds, the surface-modified (SM) ruthenium nanorods having a dominant active facet of hcp (100) through chemisorbed oxygen and OH groups (SMRu-NRs@NF) are rationally synthesized through the surfactant coordination method. SMRu-NRs@NF exhibits excellent hydrogen evolution in acid and alkaline solutions with an ultralow overpotential of 215 and 185 mV reaching 1000 mA cm-2, respectively. Moreover, it has also shown brilliant oxygen evolution electrocatalysis in alkaline solution with a low potential of 1.58 V to reach 1000 mA cm-2. It also exhibits high durability over 143 h for the evolution of oxygen and hydrogen at 1000 mA cm-2. Density functional theory studies confirmed that surface modification of a ruthenium nanorod with chemisorbed oxygen and OH groups can optimize the reaction energy barriers of hydrogen and oxygen intermediates. The surface-modified ruthenium nanorod strategy paves a path to develop the practical water splitting electrocatalyst.

Deceptive orbital confinement at edges and pores of carbon-based 1D and 2D nanoarchitectures.

The electronic structure defines the properties of graphene-based nanomaterials. Scanning tunneling microscopy/spectroscopy (STM/STS) experiments on graphene nanoribbons (GNRs), nanographenes, and nanoporous graphene (NPG) often determine an apparent electronic orbital confinement into the edges and nanopores, leading to dubious interpretations such as image potential states or super-atom molecular orbitals. We show that these measurements are subject to a wave function decay into the vacuum that masks the undisturbed electronic orbital shape. We use Au(111)-supported semiconducting gulf-type GNRs and NPGs as model systems fostering frontier orbitals that appear confined along the edges and nanopores in STS measurements. DFT calculations confirm that these states originate from valence and conduction bands. The deceptive electronic orbital confinement observed is caused by a loss of Fourier components, corresponding to states of high momentum. This effect can be generalized to other 1D and 2D carbon-based nanoarchitectures and is important for their use in catalysis and sensing applications.

Mutations profile of polycythemia vera and essential thrombocythemia among Japanese children.

BACKGROUND: Acquired somatic mutations of JAK2 have been reported to play a pivotal role in the pathogenesis of BCR-ABL1-negative myeloproliferative neoplasm (MPN). However, the molecular characteristics of childhood MPN remain to be elucidated. PATIENT AND METHODS: We investigated a group of pediatric patients diagnosed either with essential thrombocythemia (ET; N = 9) or polycythemia vera (PV; N = 4) according to WHO criteria (median age = 10 years; range 1.5-15 years) in whom direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, ASXL1, CBL, IDH1, and IDH2. More sensitive allele specific polymerase chain reaction was used for JAK2(V617F) genotyping. RESULTS: We found three patients harbor JAK2(V617F) mutation (2/9 ET and 1/4 PV). Bone marrow examination showed small and large megakaryocytes with dysplastic features in JAK2(V617F)-positive ET patients compared to those without JAK2(V617F). We identified a previously unrecognized missense mutation at codon 1230 in exon 12 of ASXL1 gene in ET and PV patients (1/9 ET and 1/4 PV). Otherwise, no genetic alterations could be detected in JAK2 exon 12, MPL, TET2, CBL, IDH1, and IDH2 in all ET and PV patients. CONCLUSION: Although JAK2 mutations in childhood ET and PV are not as frequent as reported in adult patients, JAK2 is the most frequently mutated gene in childhood MPN known so far. Owing to the presence of childhood MPN without any genetic alterations in JAK2, MPL, TET2, ASXL1, CBL, IDH1, and IDH2, new biological markers have to be found.

Unresectable pancreatic cancer: arterial embolization to achieve a single blood supply for intraarterial infusion of 5-fluorouracil and full-dose IV gemcitabine.

OBJECTIVE: Response rates to systemic chemotherapy for unresectable pancreatic cancer are low. The purposes of this phases 1 and 2 study of intraarterial therapy were to ascertain the recommended dose of intraarterial chemoinfusion and to evaluate the efficacy and safety of this therapy. SUBJECTS AND METHODS: Pancreatic arteries originating from the superior mesenteric artery (the anterior and posterior inferior pancreaticoduodenal and the dorsal pancreatic) were embolized to achieve a single blood supply from the celiac artery to manage pancreatic cancer, and a catheter-port system was placed. Intraarterial 5-fluorouracil (5-FU) and IV gemcitabine (fixed dose of 1000 mg/m(2)) were administered. In phase 1, doses of 5-FU were increased from 750 to 1000 mg/m(2). In phase 2, tumor response, toxicity, and survival time were assessed. RESULTS: A total of 20 patients were enrolled. In 19 patients (95%), the technique to unify the pancreatic blood supply was successful. No severe toxicity was observed with escalation of the 5-FU dose. The tumor response rate was 68.8%. The median overall survival time was 9.8 months and the progression-free survival time, 6.0 months. The grade 3 toxicities neutropenia (15.8%) and thrombocytopenia (5.3%) occurred. CONCLUSION: In intraarterial administration of 5-FU at a dose of 1000 mg/m(2) combined with full-dose systemic gemcitabine for unresectable pancreatic cancer, the toxicity rate was acceptable, and response rate and survival time improved over those for treatment with gemcitabine alone.

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

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

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

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

Recurrent brain abscess induced by pulmonary arteriovenous fistula.

Brain abscess associated with an arteriovenous fistula (AVF) is sometimes difficult to diagnose and tends to recur. We report a case of recurrent brain abscess due to a pulmonary AVF (PAVF). A 69-year-old woman with a mass in the left cerebral peduncle had taken a progressively worse and shown decorticate rigidity. After an intravenous antibiotic for fever of unknown origin was changed, her condition gradually improved. She was discharged with the help of a cane. Thirty-one months later, she suffered left hemiparesis. Magnetic resonance imaging revealed a cystic mass in the right lateral frontal lobe. At surgery, we confirmed pus in the cyst. A PAVF was detected and was treated with coil embolization. The left hemiparesis improved and the postoperative course was uneventful. Exhaustive study is absolutely necessary to detect the etiology of recurrent brain abscess and to achieve a cure.