Publications by authors named "Noriyuki Watanabe"

61 Publications

Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus.

Biochem Biophys Res Commun 2021 Aug 12;567:1-8. Epub 2021 Jun 12.

Department of Virology II, National Institute of Infectious Diseases, 162-8640, Tokyo, Japan. Electronic address:

Natural product-derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compounds threo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted from Crataegus cuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds #106 and #110 specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound #106 also inhibited the replication and production of hepatitis A virus. Our findings suggest that C. cuneate is a new source for novel anti-hepatitis virus drug development.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.022DOI Listing
August 2021

Infected aortic aneurysm caused by Streptococcus pyogenes: A case report.

J Infect Chemother 2021 Apr 1;27(4):647-649. Epub 2020 Dec 1.

Department of Laboratory Medicine, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address:

We reported the case with infected abdominal aortic aneurysm (AAA) caused by Streptococcus (S.) pyogenes. A seventy-seven-year-old man, who had the history of uncontrolled diabetes mellitus (DM), complained fever and abdominal pain. Abdominal computed tomography scan revealed the aneurysm above common iliac artery with false lumen. On admission, laboratory tests found marked elevation of inflammatory biomarkers. Thereby the infected AAA was suspected and blood culture was taken. The administration of meropenem (MEPM) and daptomycin (DAP) was started. Next day he underwent abdominal aortic replacement with prosthetic graft and debridement because of persistent abdominal pain and the enlargement of aneurysm. S. pyogenes in blood culture samples was identified by Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry. Same result was obtained from the tissue samples of the resected AAA. Then the diagnosis of infected AAA caused by S. pyogenes was made. Since isolated S. pyogenes showed the susceptibility to antibiotics tested including penicillin, antibiotics were changed to ampicillin (ABPC) for the de-escalation of antibiotics. He had kept the administration of ABPC for 4 weeks and transferred to another hospital for the further treatment of DM. The aneurysms by S. pyogenes are extremely rare, but we should note that S. pyogenes could induce the aneurysms.
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http://dx.doi.org/10.1016/j.jiac.2020.11.008DOI Listing
April 2021

MCPIP1 reduces HBV-RNA by targeting its epsilon structure.

Sci Rep 2020 11 27;10(1):20763. Epub 2020 Nov 27.

Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan.

Hepatitis B virus (HBV) is the major causative factor of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. We previously demonstrated that a proinflammatory cytokine IL-1β reduced the level of HBV RNA. However, the mechanism underlying IL-1β-mediated viral RNA reduction remains incompletely understood. In this study, we report that immune regulator Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) can reduce HBV RNA in hepatocytes. MCPIP1 expression level was higher in the liver tissue of HBV-infected patients and mice. Overexpression of MCPIP1 decreased HBV RNA, whereas ablating MCPIP1 in vitro enhanced HBV production. The domains responsible for RNase activity or oligomerization, were required for MCPIP1-mediated viral RNA reduction. The epsilon structure of HBV RNA was important for its antiviral activity and cleaved by MCPIP1 in the cell-free system. Lastly, knocking out MCPIP1 attenuated the anti-HBV effect of IL-1β, suggesting that MCPIP1 is required for IL-1β-mediated HBV RNA reduction. Overall, these results suggest that MCPIP1 may be involved in the antiviral effect downstream of IL-1β.
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http://dx.doi.org/10.1038/s41598-020-77166-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699622PMC
November 2020

Thoracic aortic mycotic aneurysm due to Staphylococcus argenteus: A case report.

J Infect Chemother 2020 Nov 21;26(11):1213-1215. Epub 2020 Aug 21.

Department of Cardiovascular Surgery, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.

Staphylococcus argenteus was subdivided as a novel species from Staphylococcus aureus in 2014. We herein report a case of mycotic aneurysm caused by S. argenteus. A 59-year-old woman with diabetes and schizophrenia visited at the emergency room because of falling. Chest computed tomography revealed a left humerus fracture and a thoracic aortic aneurysm. With her elevated WBC count and CRP level, she was suspected to have a mycotic aneurysm. After being transferred to our hospital, vascular graft replacement surgery was performed. Isolates of blood cultures and surgical specimens were identified as S. argenteus by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MAS MALDI Biotyper Ver. 8.0). Although S. argenteus lacks staphyloxanthin, a carotenoid pigment, it is coagulase positive. In addition to traditional and automated biochemical identification systems, even MALDI-TOF MAS may misidentify the organism as S. aureus depending on its version. S. argenteus should be considered when coagulase-negative Staphylococcus like colonies are obtained from samples of S. aureus infection. To our knowledge, this is the first case of aortic mycotic aneurysm caused by S. argenteus in Japan. Although S. argenteus is considered less virulent than Staphylococcus aureus, we should closely monitor the prevalence and the clinical impact of this pathogen on community-acquired infections and health care-associated infections.
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http://dx.doi.org/10.1016/j.jiac.2020.05.003DOI Listing
November 2020

High fibrin/fibrinogen degradation product value as a risk factor for progressive remote traumatic intracranial haemorrhage following neurosurgery.

Br J Neurosurg 2020 Jun 12:1-4. Epub 2020 Jun 12.

Department of Neurosurgery, University of Tsukuba, Tsukuba, Japan.

Remote traumatic intracranial haemorrhage (RTIH) may develop after neurosurgery. Recognition of the risk factors for RTIH before surgery might be of great value. The purpose of this study was to verify if the fibrin/fibrinogen degradation product (FDP) value may be a risk factor for RTIH. This was a retrospective study of the data of 56 patients with traumatic intracranial hematomas shown on initial computed tomography (CT) who were treated with craniotomy or decompressive craniectomy and underwent a follow-up CT at a single centre over a period of approximately 10.5 years. We divided the patients into 2 groups: those who developed RTIH (Positive: P-group) and those who did not (Negative: N-group). We compared the 2 groups in terms of not only the laboratory data before surgery, but also patient age, sex, antiplatelet/antithrombotic medications received, cause of injury, and GCS score on arrival. RTIH was observed in 22 patients (P-group, 39.3%). The FDP value was the only significant risk factor identified in this study ( = 0.00076). The cut-off value was estimated on the basis of the area under the receiver operating characteristic (ROC) curve. The cut-off FDP value was 120 µg/mL (63.6% sensitivity and 85.3% specificity). FDP levels over 120 µg/mL were determined to be a risk factor for progressive RTIH after neurosurgery. We suggest the FDP level be checked before surgery for traumatic intracranial haemorrhage and follow-up CT be done as soon as possible after the surgery if the serum FDP level is over 120 µg/mL.
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http://dx.doi.org/10.1080/02688697.2020.1775788DOI Listing
June 2020

[A Case of Medullary Carcinoma of the Colon with Poor Prognosis].

Gan To Kagaku Ryoho 2020 Apr;47(4):637-639

Dept. of Surgery, Suita Municipal Hospital.

An 87-year-oldwoman was referredowing to lightheadedness. Severe anemia(Hb 3.9 g/dL)was detected, and colonoscopy revealeda circumferential elevatedlesion at the transverse colon(Group 5, por). The patient was diagnosed with colon cancer(cT4a, N0, M0, Stage Ⅱ), andright hemicolectomy was performed. Immunochemical analysis showedthat the lesion was MLH1- andPMS2- and confirmed a diagnosis of medullary carcinoma. Although the patient was discharged 48 days after surgery without any incident, she was readmitted because of lower leg edema. Liver metastasis and peritoneal dissemination were suspectedon performing computedtomography, andthe patient died3 5 days after readmission. Medullary carcinoma has molecular pathological features such as methylation of the promoter region andassociatedattenuation of MLH1 protein expression, as well as microsatellite instability. The prognosis for medullary carcinoma is relatively good comparedto that for poorly differentiatedad enocarcinoma, though the present case hada poor prognosis. Herein, we report a literature review.
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April 2020

[Pregnancy-Associated Stage Ⅳ Gastric Cancer with No Recurrence for a Long Time-A Case Report].

Gan To Kagaku Ryoho 2019 Dec;46(13):2565-2567

Dept. of Surgery, Suita Municipal Hospital.

A 28-year-oldwoman visiteda clinic with a complaint of epigastralgia 3 months after delivery. She was diagnosedwith gastritis andtreatedwith medication. Two months later, in January 2006, she was admittedto our hospital with a complaint of dysphagia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer in the lesser curvature of the cardia, and abdominal CT scan showed wall thickening of the upper gastric body. No apparent distant metastases were found. The patient underwent total gastrectomy with D2 lymph node dissection in February 2006. Although there was no peritoneal dissemination, the patient testedpositive in peritoneal lavage cytology. The postoperative pathological diagnosis was gastric cancer pT4aN2M1(P0CY1H0), Stage Ⅳ. She was discharged on postoperative day 22. S-1 monotherapy(100mg/day, day 1- 28q6wks)was performedfor 1 year on an outpatient basis. For 13 years and1 0 months after the surgery, no apparent recurrences of gastric cancer have been observed. In gastric cancers associated with pregnancy, it is difficult to distinguish between perinatal symptoms andsymptoms of gastric disease. Therefore, endoscopic examination shouldbe performedfor perinatal patients presenting with persistent gastrointestinal symptoms.
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December 2019

[Curative Resection for Liver Metastasis Ten Years after Surgery for Rectosigmoid Cancer-A Case Report].

Gan To Kagaku Ryoho 2019 Dec;46(13):2372-2374

Dept. of Surgery, Suita Municipal Hospital.

Here, we report the case of a 73-year-oldfemale patient, who previously underwent high anterior resection for rectosigmoidcancer at the age of 63. Her scheduled5 years of follow-up after colorectal surgery hadbeen finished, but she kept undergoing endoscopic mucosal resection for colorectal polyps every 1 or 2 years since then. Blood examination 10 years 6 months after surgery for rectosigmoidcancer revealedthat the value of her serum CEA was 5.5 ng/mL, which was slightly higher than the normal range. Contrast-enhancedCT showedan irregular-shapedtumor with a diameter of 3 cm in which the contrast of the peripheral area was mainly emphasized. When combining the results of MRI and PET-CT examinations, the liver tumor was clinically diagnosed as either intrahepatic cholangiocarcinoma or metastatic liver cancer. Since the first choice of therapy was tumor resection for both diagnoses, S8 subsegmental hepatectomy was performed 10 years 8 months after surgery for rectosigmoidcancer. HE staining of the resectedspecimen showedwell or moderately differentiatedad enocarcinoma, andits immunostaining findings were as follows: CDX-2: positive, CK20: positive, CK7: negative. It was pathologically diagnosed as liver metastasis from rectal cancer. It is rare for colorectal cancer to have metachronous liver metastasis more than 10 years after surgery. However, in any case where a tumor marker for colorectal cancer increases, it is necessary to examine carefully with the possibility of any metastasis in mind.
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December 2019

Bloodstream infection by multidrug-resistant Streptococcus oralis in a leukemic patient with febrile neutropenia after hematopoietic stem cell transplantation.

Transpl Infect Dis 2020 Apr 20;22(2):e13246. Epub 2020 Jan 20.

Department of Laboratory Medicine, Saitama Medical University International Medical Center, Saitama, Japan.

We reported the case of a patient with leukemia who developed febrile neutropenia after hematopoietic stem cell transplantation. Blood culture results revealed the presence of Streptococcus oralis, while antimicrobial susceptibility testing showed the resistance to penicillin and cephem. Furthermore, isolates were not susceptible to either meropenem or daptomycin but not to vancomycin. S oralis is known to belong to Streptococcus mitis group and be a causative agent of bacteremia in the neutropenic patients, but multidrug resistance of S oralis is rare. Our findings suggest that we might pay attention to the emergence of the microorganisms acquiring multidrug resistance in neutropenic patients.
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http://dx.doi.org/10.1111/tid.13246DOI Listing
April 2020

Malignant transformation of pleomorphic xanthoastrocytoma and differential diagnosis: case report.

BMC Neurol 2020 Jan 15;20(1):21. Epub 2020 Jan 15.

Departments of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.

Background: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic glioma, characterized by large pleomorphic and frequently multinucleated cells, spindle and lipidized cells, a dense pericellular reticulin network, and numerous eosinophilic granular bodies according to the grade II glial tumor standards of the World Health Organization's (WHO) 2016 guidelines. PXA rarely transforms into anaplastic PXA or glioblastoma (GBM) and anaplastic PXA, classified as WHO grade III, has a more aggressive clinical behavior with poorer prognosis than PXA.

Case Presentation: Here we describe an unusual case of PXA in a 19-year-old woman, first admitted with headache and a mass in the left temporal lobe in 2005 that was removed. Twelve years later, she returned with left temporal headache, diplopia and tinnitus. A local tumor recurrence was found, and a second resection was performed. The specimen showed highly malignant findings, such as necrosis, microvascular proliferation, and multiple mitoses. The integrated diagnosis was made as high grade glioma, probably derived from PXA. Immunohistochemical (IHC) stains were positive for oligo2, and approximately 21% positive for Ki-67, while negative for CD34, IDH1 R132H. INI1 and ATRX were retained. As the histological classification was glioblastoma, the patient received GBM-appropriate chemotherapy and radiation therapy and outpatient follow-ups have demonstrated no obvious symptoms for 1 year after surgery. Additional molecular analyses found BRAF V600E mutations in both resections, supporting the idea that the recurrent tumor had derived from PXA.

Conclusions: This case highlights the complexities of differential diagnosis based on the World Health Organization's 2016 guidelines. More integrated criteria to differentiate anaplastic PXA from GBM and epithelioid GBM, combined with genetic screening results, might be needed.
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http://dx.doi.org/10.1186/s12883-020-1601-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961389PMC
January 2020

Establishment of infectious genotype 4 cell culture-derived hepatitis C virus.

J Gen Virol 2020 02 20;101(2):188-197. Epub 2019 Dec 20.

Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.

To establish infectious genotype 4a (GT4a) cell culture-derived hepatitis C virus (HCVcc), we constructed full-length ED43 and 12 mutants possessing single or double mutations that increase ED43 replicon replication, and performed cell culture after RNA transfection. Sequential long-term culture of full-length ED43 RNA-transfected cells showed increased viral production in two ED43 mutants named ED43 QK/SI and TR/SI among the tested clones. These ED43 mutants possessed a common mutation, R1405G, in the NS3 helicase region and another mutation, D2413G or V2414A, in the NS5a-NS5b cleavage site. Furthermore, serial reinfection of naïve Huh7.5.1 cells accelerated peak HCV production at an earlier time point after every infection. After the fourth infection, we found a common mutation, R1405G, and six additional mutations in both ED43 QK/SI and TR/SI mutants. All seven mutations supported continuous viral production for more than 40 days in both ED43 QS-7M (QK/SI with seven mutations) and ED43 TS-7M (TR/SI with seven mutations). In addition, ED43 TS-7M did not require additional mutations for continuous virus culture up to 124 days. Both ED43 QS-7M and TS-7M were sensitive to the neutralizing E2 antibodies HCV1 and AR3A and the direct-acting antivirals, simeprevir, ledipasvir and sofosbuvir. In conclusion, we established an infectious ED43 strain containing adaptive mutations, which is important for the analysis of HCV genotype-specific pathogenesis, development of pan-genotypic agents and analysis of drug resistance.
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http://dx.doi.org/10.1099/jgv.0.001378DOI Listing
February 2020

Laparoscopic colectomy after transcatheter aortic valve implantation in an elderly patient with obstructive descending colon cancer and severe aortic stenosis: a case report.

Surg Case Rep 2019 Jun 24;5(1):102. Epub 2019 Jun 24.

Department of Surgery, Suita Municipal Hospital, Kishibeshinmachi 5-7, Suita, Osaka, 564-8567, Japan.

Background: The demand for laparoscopic colectomy is increasing due to greater number of elderly colon cancer patients, and it is important to evaluate existing comorbidities to ensure perioperative safety. Aortic stenosis (AS) is one of the most common heart diseases in the elderly, and elderly cancer patients with severe AS may be considered ineligible for optimal cancer treatment if they cannot endure surgical aortic valve replacement (SAVR). Recently, transcatheter aortic valve implantation (TAVI) has become a valid option in patients who are high risk for SAVR. We herein present the first case of an elderly cancer patient with severe AS who underwent laparoscopic colectomy after TAVI.

Case Presentation: An 87-year-old woman with a history of multiple cardiovascular diseases was diagnosed with obstructive descending colon cancer and initially underwent colonic stenting. However, as preoperative echocardiography revealed severe AS, she underwent TAVI prior to the colectomy to reduce perioperative risk. TAVI was chosen instead of SAVR due to high SAVR mortality risk, and laparoscopic colectomy was performed 22 days after TAVI. Her postoperative course was uneventful, and she was discharged 14 days later without any deterioration in general condition. No recurrence was observed at more than 1 year, even without adjuvant therapy.

Conclusion: TAVI facilitated subsequent laparoscopic colectomy in an elderly cancer patient with severe AS. Our case report shows that TAVI may enable further cancer treatment even in patients with severe AS, who may otherwise be considered not suitable for such treatments.
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http://dx.doi.org/10.1186/s40792-019-0662-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591332PMC
June 2019

[A Case of Hepatocellular Carcinoma Complicated with Idiopathic Thrombocytopenic Purpura].

Gan To Kagaku Ryoho 2019 Apr;46(4):799-801

Dept. of Surgery, Suita Municipal Hospital.

The patient was a 72-year-oldwoman. She had been diagnosed with idiopathic thrombocytopenic purpura(ITP), hepatitis B, and diabetes mellitus. She was admitted to our hospital because of anemia andvomiting of blood vomiting and was diagnosed with hepatocellular carcinoma at S6. A splenectomy was performed, with a temporary improvement of her platelet count. We tried to control the platelet count with medication and performed transcatheter arterial embolization(TACE)3 times. However, the tumor size decreased only slightly anda new tumor was observed on S2. Therefore, we increased the patient's platelet count to 109×10 4/mL and performed a partial hepatectomy of 4 lesions. The postoperative complications included intraabdominal abscess, but there was no bleeding and the patient was discharged on POD 114. Platelet count is often difficult to maintain in patients diagnosed with ITP. We report our experiences and also provide a discussion of a case of operated hepatocellular carcinoma complicated with refractory ITP.
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April 2019

[Role of Palliative Chemotherapy for Peritonitis Carcinomatosa of Inoperable Advanced Gastric Cancer].

Gan To Kagaku Ryoho 2019 Apr;46(4):763-765

Dept. of Surgery, Suita Municipal Hospital.

We report a case of peritoneal dissemination of gastric cancer in which the QOL was maintained with a less-than-optimum dose of anticancer agent. A 64-year-old man underwent total gastrectomy for corpus gastric cancer without distant metastasis performedas an open-laparotomy. Peritoneum disseminations were observed in the left sub-diaphragmatic space and back side of the mesocolon, andthe tumor passedd irectly to the superior mesenteric vein of transverse mesocolon. As a first- line chemotherapy, G-SOX therapy(S-1 80mg/day/body and oxaliplatin 100mg/m2)was administered for 15 courses. After these courses, the disease was categorized as PD. Next, RAM/PTX(ramucirumab 8mg/kg andpaclitaxel 80mg/m2) were administered as second-line chemotherapy. However, the PTX, especially causedprolongedad verse effects such as G4- leveledbloodtoxicity andsevere general fatigue. Therefore, we administereda lower dose of PTX than the original optimal minimum dose. This lower dose chemotherapy resulted in effective changes such as decreased pain and general fatigue and resolution of the bloodtoxicity. As a result, the patient's QOL improved, and his condition has been maintained as SD for 2 years after the operation. For these reasons, this ordinary chemotherapy may be used as a palliative chemotherapy.
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April 2019

Hepatic gas gangrene caused by Clostridium novyi.

Anaerobe 2019 Jun 4;57:90-92. Epub 2019 Apr 4.

Department of Laboratory Medicine, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address:

We report the case of a patient with advanced gastric cancer and multiple liver metastases, who presented with bacteremia and hepatic gas gangrene caused by Clostridium novyi (C. novyi). The gas gangrene caused abscesses to form within metastatic lesions. This case highlights the antitumor effects of C. novyi in human.
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http://dx.doi.org/10.1016/j.anaerobe.2019.03.018DOI Listing
June 2019

[A Case of a Duodenal GIST Observed as a Non-Functional Pancreatic Neuroendocrine Tumor].

Gan To Kagaku Ryoho 2019 Mar;46(3):589-591

Dept. of Surgery, Suita Municipal Hospital.

A 67-year-oldman was referredto our hospital because his CEA level was increasing. In March 2007, abdominal computed tomography(CT)showedthe presence of a tumor(30mm in diameter)in the pancreatic head. Upon close inspection, the patient was diagnosed with a non-functional pancreatic neuroendocrine tumor and was observed. In September 2016, the patient showedhyperglycemia, liver dysfunction, andelevation of tumor markers. CT revealeda tumor(42mm in diameter) in the pancreatic head. It hadincreasedmore than before. We diagnosedhim with a gastrointestinal stromal tumor(GIST)of the duodenum based on endoscopic ultrasound-guided fine-needle aspiration biopsy and performed pancreaticoduodenectomy. Immunohistochemical staining showedpositive c-kit, andmore than 10%positive MIB-1. Currently, the patient is alive after the surgery.
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March 2019

Transvenous Embolization of Dural Arteriovenous Fistula of the Anterior Condylar Confluence via the Intercavernous Sinus Assisted by Bone Subtraction Computed Tomography Angiography.

World Neurosurg 2019 06 9;126:151-155. Epub 2019 Mar 9.

Department of Neurosurgery, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Background: Dural arteriovenous fistulae (dAVFs) of the anatomically complex anterior condylar confluence (ACC) are often examined by computed tomography (CT) angiography and conventional angiography before treatment. Contrasted vessels often overlap with skull bones in enhanced CT scan and make it difficult to detect the shunt point of the dAVF. Bone subtraction CT angiography (BSCTA) can overcome this limitation and allow for superior imaging of dAVFs that may help to find an alternative access for catheterization.

Case Description: An 80-year-old woman suffered from right ear tinnitus, headache, and an audible bruit. Preoperative imaging showed a dAVF of the ACC. It was fed by the bilateral ascending pharyngeal artery, drained to the internal jugular vein (IJV) via the inferior petrosal sinus, and had an intraosseous shunt pouch. We therefore performed transvenous embolization (TVE) via the intercavernous sinus because the angle between the anterior condylar vein and the IJV was too sharp to catheterize vessels through the ipsilateral IJV.

Conclusions: Understanding the inherently complex and individually unique venous anatomy of the ACC is crucial for treatment of dAVFs. BSCTA is an effective visualization technique for dAVFs of the ACC and allows for precise preoperative vascular structure evaluation. We suggest that in the case of the angle between the ACV and the IJV being too sharp to catheterize vessels through the ipsilateral IJV, TVE via the intercavernous sinus can be efficiently used.
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http://dx.doi.org/10.1016/j.wneu.2019.02.175DOI Listing
June 2019

[A Case of Extramedullary Plasmacytoma of the Stomach Detected Due to Severe Anemia].

Gan To Kagaku Ryoho 2019 Jan;46(1):100-102

Dept. of Surgery, Suita Municipal Hospital.

A 78-year-oldwoman was referredfor exertional dyspnea. Severe anemia(Hb 4.2 g/dL)was detected, and upper endoscopy revealeda giant ulcer at the posterior wall of the gastric body. Computedtomography showeda mass protruding from the gastric wall, suggestive of a submucosal tumor. Although biopsy did not confirm a diagnosis, we performed distal gastrectomy to control the bleeding. The pathological findings and systemic examination confirmed a diagnosis of extramedullary plasmacytoma of the stomach. Plasmacytoma is a tumor of the bone marrow derived from plasma cells that mature from B cells. The frequency of extramedullary plasmacytoma for all plasmacytoma is about 5% and plasmacytoma derived from the stomach occurs in approximately 2%of these cases. Complete resection with lymph node dissection according to the surgical treatment of gastric cancer is recommended. Large tumors, such as that in the present case, may have a poor prognosis; thus, careful follow-up is required for the early detection of recurrence. We report a case of extramedullary plasmacytoma of the stomach with a literature review.
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January 2019

[A Case of Long-Term Control of Stage Ⅳ Gastric Cancer by Multimodal Therapy].

Gan To Kagaku Ryoho 2019 Jan;46(1):97-99

Dept. of Surgery, Suita Municipal Hospital.

An 82-year-oldwoman was admittedto our hospital because of appetite loss andwas diagnosedwith a Type 3 tumor in the lower gastric body. Pathological examination suggested moderately differentiated adenocarcinoma with negative staining for HER2 by immunohistochemistry. An abdominal CT revealedthickening of the gastric wall andparaaortic lymph node metastases. The clinical findings suggested Stage Ⅳ disease(T4aN3M1). Chemotherapy was administered with a combination of S-1 plus oxaliplatin(SOX). After 2 courses of the SOX regimen, an abdominal CT showed a reduction of the paraaor- tic lymph node metastases, and the CEA level hadd ecreasedto 6.2 ng/mL. After 7 courses of the SOX regimen, the CEA level hadincreasedto 10.1 ng/mL, and the treatment schedule was changed to a regimen of paclitaxel plus ramucirumab(PTX/ RAM). However, grade 4 neutropenia was observed after the first treatment. Distal gastrectomy with D1+lymph node dissection was performedfor local control in September 2016. The post-operative pathological findings were ypT1b2ypN2M1, ypStage Ⅳ and the chemotherapeutic effect was grade 1a. A CT scan revealedregrowth of the paraaortic lymph node 3 months after the operation. Chemotherapy was administered with a combination of capecitabine plus oxaliplatin(CapeOX). At present, the patient is being treatedwith capecitabine monotherapy in the outpatient department with no signs of tumor regrowth.
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January 2019

[Resection of a Desmoid Tumor Originating from the Greater Omentum after Surgery for Colon Cancer and Liver Metastasis-A Case Report].

Gan To Kagaku Ryoho 2018 Dec;45(13):2444-2446

Dept. of Surgery, Suita Municipal Hospital.

Here, we report the case of a 66-year-old male patient who previously underwent resection of sigmoid colon cancer and its liver metastasis. His follow-up contrast-enhanced CT scan revealed a mass shadow at around the gastrosplenic ligament, which gradually increased in size. Because it could not be pathologically diagnosed by transgastric EUS-FNA, en bloc resection wasperformed surgically for the tumor in the greater omentum. Hematoxylin-eosin staining of the resected specimen showed fibroblast-like cellswith hyperplasia of bold collagen fibersand spindle-shaped nucleus. While the immunostaining findings denied a diagnosis of mesenchymal neoplasm such as GIST, leiomyosarcoma, or schwannoma, it was pathologically diagnosed as a desmoid tumor. He has been followed up without any recurrence for 2-and-a-half years after the surgical resection. Desmoid tumors tend to be locally invasive; thus, there is the potential for local recurrence, although the frequency of distant metastasis is very low. In cases in which the tumor increases in size, en bloc resection with sufficient surgical margin should be performed. Cases of desmoid tumors originating from the greater omentum are reportedly rare; however, en bloc resection may be useful for both diagnosis and treatment of tumors of the greater omentum showing increased size that are also surgically resectable.
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December 2018

[A Case of Multiple Pulmonary Metastases of Rectal Cancer Controlled with Pulmonary Resection and Stereotactic Body Radiotherapy for Four Years].

Gan To Kagaku Ryoho 2018 Dec;45(13):2111-2113

Dept. of Surgery, Suita Municipal Hospital.

A female in her 40s underwent surgical resection for rectal cancer, and metastases in the liver, ovaries, and peritoneum in 2 stages. Multiple pulmonary metastases appeared after the second operation, and right lung middle lobectomy and left lung S8 wedge resection were performed sequentially. Because another metastatic lesion in the right lung S7 was located deep in the parenchyma, stereotactic body radiotherapy(SBRT), instead of surgery, was selected for this lesion and a right lung S8 nodule. SBRT was also performed for a new metastatic lesion in the right lung S6. Local relapse of resected or irradiated lesions was not recognized for 53 months after the first pulmonary resection, and no new lesions appeared for 20 months after the last SBRT. SBRT for pulmonary metastases of colorectal cancer can achieve good survival and local control comparable to surgery and has the advantage of safety and respiratory reserve over surgery. The combination of surgical resection and SBRT for multiple pulmonary metastases is especially beneficial for relatively young patients with jobs and/or children, because it enables patients to maintain good quality of life by avoiding systemic chemotherapy accompanied with adverse events.
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December 2018

False-positive blood culture results in patients with hematologic malignancies.

J Infect Chemother 2019 May 23;25(5):404-406. Epub 2019 Jan 23.

Department of Laboratory Medicine, Saitama Medical University International Medical Center, Saitama, Japan; Department of Laboratory Medicine, Saitama Medical University, Saitama, Japan.

Blood cultures are the most valuable tool when bacteremia is clinically suspected. Technical advances have led to the development of automated blood culture systems to detect bacterial infections. Usually positive signals in automated blood culture systems result from the proliferation of microorganisms. Cases are classified as false-positive when the automated blood culture system produces a positive signal but no microorganisms are detected on Gram-stained smears and no microorganism growth is observed in blood subcultures. False-positive blood culture results are very rare in patients with hematologic malignancies. Recently, we encountered four patients who had false-positive blood culture results. Two of the patients were diagnosed with acute leukemia, involving hyperleukocytosis and an excess of blasts. The other two patients were diagnosed with acute leukemia and diffuse large B cell lymphoma with leukocytopenia. Although hypercapnia or acidosis, apart from hyperleukocytosis, might also cause false-positive results, our cases clearly did not have these conditions. We should be aware of the possibility that false-positive blood culture results can occur in patients with leukocytopenia, as well as hyperleukocytosis. To understand the mechanisms responsible for the observed false-positive results, additional studies are needed after the accumulation of similar cases.
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http://dx.doi.org/10.1016/j.jiac.2018.12.010DOI Listing
May 2019

IL-1β/ATF3-mediated induction of Ski2 expression enhances hepatitis B virus x mRNA degradation.

Biochem Biophys Res Commun 2018 09 25;503(3):1854-1860. Epub 2018 Jul 25.

Department of Virology II, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan. Electronic address:

Hepatitis B virus (HBV) -x protein is a transcriptional regulator required for the HBV life cycle. HBx also induces complications in the host such as hepatocellular carcinoma. We previously showed that HBx mRNA is degraded by the Ski2/RNA exosome complex. In the present study, we report the regulation of this system through the control of Ski2 expression. We identified interleukin (IL) -1β as an inducer of expression from the Ski2 promoter. IL-1β induced the expression of ATF3 transcription factor, which in turn binds to cyclic AMP-responsive element sequence in the Ski2 promoter and is responsible for Ski2 promoter induction by IL-1β. We previously reported that Ski2 expression increases HBx mRNA degradation; consistent with those data, we showed here that HBx mRNA is degraded in response to IL-1β treatment. Interestingly, HBx also significantly induced Ski2 expression. To our knowledge, this is the first report to show activation of the Ski2/RNA exosome complex by both the host and HBV. Understanding the regulation of the Ski2/RNA exosome system is expected to facilitate prevention of HBx-mediated complications through targeting the posttranscriptional degradation of HBx mRNA; and will also help shedding a light on the role of RNA decay systems in inflammation.
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http://dx.doi.org/10.1016/j.bbrc.2018.07.126DOI Listing
September 2018

[A Case of Locally Advanced and Metastatic Breast Cancer Treated with Preoperative Bevacizumab Combination Chemotherapy That Attained Local Control].

Gan To Kagaku Ryoho 2018 Jul;45(7):1097-1099

Dept. of Surgery, Suita Municipal Hospital.

We report a case of a 74-year-old woman with a left breast tumor with skin infiltration. Luminal type breast cancer with lung, bone, and parasternal lymph node metastases was diagnosed. She received paclitaxel and bevacizumab treatment. After chemotherapy, the lung metastasis and parasternal lymph node metastasis had disappeared, and the breast tumor had shrunk. Mastectomy and axillary lymph node dissection were performed. She has been receiving post-operative endocrine therapy. Paclitaxel and bevacizumab combination therapy is one of the useful treatments for metastatic breast cancer with skin infiltration.
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July 2018

Primary meningeal myxoid liposarcoma with aggressive behavior after recurrence: case report.

Acta Neurochir (Wien) 2018 08 19;160(8):1557-1561. Epub 2018 Jun 19.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Although liposarcomas are the most common soft tissue sarcomas, their intracranial variants are extremely rare. Here, we present a case of a primary intracranial myxoid liposarcoma in a 23-year-old Japanese man who presented with generalized seizures and a mass in the left frontal lobe. The tumor was totally removed, and histological analyses pointed to liposarcoma. Thirteen years after his initial treatment, the patient presented with right-side weakness and local recurrence of tumor was discovered. Histology from the second resection confirmed the diagnosis of myxoid liposarcoma. Shortly after the second resection, progressive, new intracranial lesions were observed and despite a third resection, extensive intracerebral invasion by the tumor proved fatal. The histological features of myxoid liposarcoma were essentially similar with each recurrence, but the aggressive tumor behavior after the second operation did not align with expectations based on histological classification.
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http://dx.doi.org/10.1007/s00701-018-3598-5DOI Listing
August 2018

First report of the isolation of bla-producing colistin-heteroresistant Enterobacter cloacae in Japan, September 2016.

J Infect Chemother 2018 Nov 30;24(11):941-943. Epub 2018 Apr 30.

Department of Infectious Disease and Infection Control, Saitama Medical University, Saitama, Japan; Center for Clinical Infectious Diseases and Research, Saitama Medical University, Saitama, Japan.

The isolation of a carbapenem-resistant Enterobacter cloacae strain harboring the IMI-1 variant of bla carbapenemase points to the worldwide emergence of multidrug resistant bacteria as a potential source of health care infections. In this report, we describe the first isolation of E. cloacae with bla carbapenemase isolated from a Japanese patient in September 2016. The isolate was resistant to carbapenems, levofloxacin, and aminoglycosides, and heteroresistant to colistin but sensitive to fourth-generation cephalosporins. All microbiology laboratories worldwide should be made aware of these bla-producing subtypes with unusual antibiotic susceptibility profiles.
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http://dx.doi.org/10.1016/j.jiac.2018.04.004DOI Listing
November 2018

[A Case of Ruptured Anterior Communicating Artery Aneurysm with Visual Field Defects and Deteriorating to Severe Vision Loss].

Brain Nerve 2017 Oct;69(10):1149-1153

Department of Neurosurgery, Tsukuba Medical Center Hospital.

Although Terson's syndrome is a well-known cause of vision loss due to intracerebral aneurysm rupture, optic nerve neuropathy can also occur because of other causes. Here, we report such a case, i.e., a ruptured anterior communicating artery aneurysm accompanied by vision loss and visual field disturbances due to a cause other than Terson's syndrome. A 47-year-old man presented with right superior altitudinal hemianopia. Computed tomography (CT) showed subarachnoid hemorrhage (SAH), and three-dimensional CT angiography revealed an anterior communicating artery aneurysm. Coil embolization was performed. Right visual acuity degenerated to blindness in the acute stage. MRI performed on day 7 post-admission revealed that the aneurysm had swollen and made contact with the right optic disk. On the basis of the patient's clinical course, we believe that the deterioration in his visual acuity could have been due to ischemic optic neuropathy (ION) resulting from SAH, and the subsequent edema and poor blood perfusion may be attributed to spasm. In cases of visual disturbance associated with SAH, as in our case, it is important to perform MRI to evaluate the damage or risk to the optic nerve as soon as possible. (Received December 26, 2016; Accepted June 9, 2017; Published October 1, 2017).
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http://dx.doi.org/10.11477/mf.1416200883DOI Listing
October 2017

Neurological Recovery after Posterior Spinal Surgery in Patients with Metastatic Epidural Spinal Cord Compression.

Acta Med Okayama 2016 Dec;70(6):449-453

Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Metastatic epidural spinal cord compression (MESCC) is a common complication in patients with a malignant tumor, but it is difficult to decide the proper time to perform the necessary surgery. Here we analyzed the prognostic factors for postoperative walking ability. We retrospectively reviewed the cases of 112 MESCC patients treated surgically at our institute and divided them into ambulatory (n= 88) and non-ambulatory (n=24) groups based on their American Spinal Injury Association (ASIA) Impairment Scale grades at the final follow-up. We also classified the patients preoperatively using the revised Tokuhashi score. We assessed the correlation between preoperative or intraoperative factors and postoperative walking ability in both groups. Of the 10 patients classified preoperatively as grade A or B, 2 (20% ) were ambulatory at the final follow-up. Of the 102 patients classified preoperatively as grade C, D or E, 86 (84% ) were ambulatory at the final follow-up (p<0.001). There were no significant differences between the groups in the average total Tokuhashi score. Our analysis revealed that the severity of paralysis significantly affects neurological recovery in patients with MESCC. Patients with MESCC should receive surgery before the preoperative ASIA Impairment Scale grade falls below grade C.
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http://dx.doi.org/10.18926/AMO/54807DOI Listing
December 2016

Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus.

Sci Rep 2016 06 27;6:28688. Epub 2016 Jun 27.

Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Directly acting antivirals recently have become available for the treatment of hepatitis C virus (HCV) infection, but there is no prophylactic vaccine for HCV. In the present study, we took advantage of the properties of Japanese encephalitis virus (JEV) to develop antigens for use in a HCV vaccine. Notably, the surface-exposed JEV envelope protein is tolerant of inserted foreign epitopes, permitting display of novel antigens. We identified 3 positions that permitted insertion of the HCV E2 neutralization epitope recognized by HCV1 antibody. JEV subviral particles (SVP) containing HCV-neutralization epitope (SVP-E2) were purified from culture supernatant by gel chromatography. Sera from mice immunized with SVP-E2 inhibited infection by JEV and by trans-complemented HCV particles (HCVtcp) derived from multi-genotypic viruses, whereas sera from mice immunized with synthetic E2 peptides did not show any neutralizing activity. Furthermore, sera from mice immunized with SVP-E2 neutralized HCVtcp with N415K escape mutation in E2. As with the SVP-E2 epitope-displaying particles, JEV SVPs with HCV E1 epitope also elicited neutralizing antibodies against HCV. Thus, this novel platform harboring foreign epitopes on the surface of the particle may facilitate the development of a bivalent vaccine against JEV and other pathogens.
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http://dx.doi.org/10.1038/srep28688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922013PMC
June 2016
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