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1.
No Shinkei Geka ; 52(2): 374-379, 2024 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-38514127

RESUMO

Preoperative simulation is essential to safely complete neurosurgical procedures. A vascular-oriented approach is important in cerebrovascular disorder surgery, considering anatomical variations among individuals. Particularly, subarachnoid hemorrhage surgery requires a detailed simulation of a safe dissection procedure, considering the rupture point of the aneurysm, and combined computed tomography or magnetic resonance imaging images with cerebral angiography can be useful. We present a case of subarachnoid hemorrhage and introduce the preoperative simulation performed at our hospital.


Assuntos
Aneurisma Roto , Transtornos Cerebrovasculares , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Craniotomia , Procedimentos Neurocirúrgicos/métodos , Aneurisma Roto/cirurgia
2.
Artigo em Inglês | MEDLINE | ID: mdl-38547854

RESUMO

BACKGROUND: Postoperative hyperperfusion syndrome (PHS) is a well-known complication following superficial temporal artery (STA)-middle cerebral artery (MCA) bypass for moyamoya disease (MMD). The early detection of postoperative radiological hyperperfusion (PRH), characterized by a transient increase in local cerebral blood flow (CBF), is crucial for the early diagnosis of PHS. This study aimed to investigate the effectiveness of waveform analysis for early PRH detection. METHODS: We reviewed 52 consecutive patients who underwent STA-MCA bypass for MMD. Patients were divided into PRH and non-PRH groups based on the postoperative/preoperative CBF ratio. We collected the intraoperative bypass graft waveform and bypass flow data using a flowmeter. The pulsatile index (PI), an indicator of peripheral vascular resistance (PVR), was calculated from bypass flow data. Next, the newly proposed index of PVR, the ratio of the time from peak to 50% decay and to 100% decay (RT50), was calculated through waveform analysis. The values were then compared between the PRH and non-PRH groups. RESULTS: Twenty-seven of the 52 patients met the inclusion criteria. Fourteen of these 27 patients showed PRH. The RT50, but not the PI, was significantly higher in the PRH group. Linear regression analysis revealed a significant correlation between the RT50 and PI. In the receiver operating characteristic for predicting PRH, the area under the curve of RT50 was 0.750, with a cutoff value of 0.255, a sensitivity of 0.928, and a specificity of 0.500. CONCLUSIONS: The RT50 obtained from waveform analysis is associated with PVR and can be useful for the early detection of PRH in patients with MMD.

3.
Int J Surg Pathol ; : 10668969231204955, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880949

RESUMO

Ulcerative colitis (UC) is an intractable disease that affects young adults. Histological findings are essential for its diagnosis; however, the number of diagnostic pathologists is limited. Herein, we used a no-code artificial intelligence (AI) platform "Teachable Machine" to train a model that could distinguish between histological images of UC, non-UC coloproctitis, adenocarcinoma, and control. A total of 5100 histological images for training and 900 histological images for testing were prepared by pathologists. Our model showed accuracies of 0.99, 1.00, 0.99, and 0.99, for UC, non-UC coloproctitis, adenocarcinoma, and control, respectively. This is the first report in which a no-code easy AI platform has been able to comprehensively recognize the distinctive histologic patterns of UC.

4.
Acta Neurochir (Wien) ; 165(12): 4213-4219, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37726426

RESUMO

PURPOSE: The anatomical association between the lesion and the perforating arteries supplying the pyramidal tract in insulo-opercular glioma resection should be evaluated. This study reported a novel method combining the intra-arterial administration of contrast medium and ultrahigh-resolution computed tomography angiography (UHR-IA-CTA) for visualizing the lenticulostriate arteries (LSAs), long insular arteries (LIAs), and long medullary arteries (LMAs) that supply the pyramidal tract in two patients with insulo-opercular glioma. METHODS: This method was performed by introducing a catheter to the cervical segment of the internal carotid artery. The infusion rate was set at 3 mL/s for 3 s, and the delay time from injection to scanning was determined based on the time-to-peak on angiography. On 2- and 20-mm-thick UHR-IA-CTA slab images and fusion with magnetic resonance images, the anatomical associations between the perforating arteries and the tumor and pyramidal tract were evaluated. RESULTS: This novel method clearly showed the relationship between the perforators that supply the pyramidal tract and tumor. It showed that LIAs and LMAs were far from the lesion but that the proximal LSAs were involved in both cases. Based on these results, subtotal resection was achieved without complications caused by injury of perforators. CONCLUSION: UHR-IA-CTA can be used to visualize the LSAs, LIAs, and LMAs clearly and provide useful preoperative information for insulo-opercular glioma resection.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Angiografia por Tomografia Computadorizada , Córtex Cerebral/cirurgia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Artéria Cerebral Média/patologia , Angiografia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/cirurgia , Artérias Cerebrais/patologia
5.
Br J Cancer ; 128(12): 2206-2217, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37076565

RESUMO

BACKGROUND: Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity. METHODS: We performed the genomic, transcriptomic, proteomic and metabolomic analysis of 39-77 ICC tumour samples and eleven normal samples. Further, we analysed their cell proliferation and viability. RESULTS: We demonstrated that intra-tumoral heterogeneity of ICCs with distinct driver genes per case exhibited neutral evolution, regardless of their tumour stage. Upregulation of BCAT1 and BCAT2 indicated the involvement of 'Val Leu Ile degradation pathway'. ICCs exhibit the accumulation of ubiquitous metabolites, such as branched-chain amino acids including valine, leucine, and isoleucine, to negatively affect cancer prognosis. We revealed that this metabolic pathway was almost ubiquitously altered in all cases with genomic diversity and might play important roles in tumour progression and overall survival. CONCLUSIONS: We propose a novel ICC onco-metabolic pathway that could enable the development of new therapeutic interventions.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Proteômica , Aminoácidos de Cadeia Ramificada , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/genética , Transaminases
6.
Oper Neurosurg (Hagerstown) ; 24(4): 404-409, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36701690

RESUMO

BACKGROUND: Cranioplasty is a surgical procedure widely performed for repairing cranial defects caused by external decompression surgery for cerebrovascular disease or traumatic brain injury. We devised a new cranioplasty method using artificial bone made up of ultra-high molecular-weight polyethylene, with serrated wings on the edge. We named this newly designed artificial bone as Merlon shape. OBJECTIVE: To describe our initial experience with the Merlon shape and evaluate its usefulness and safety in cranioplasty. METHODS: The serrated wings of the Merlon shape were preoperatively designed for solid fixation and improving cosmetic results by reducing the thickness of the artificial bone. We evaluated 25 patients who underwent cranioplasty with the Merlon shape between December 2018 and December 2021. The causes of bone defects in these patients (male: 9, female: 16; median age: 62 years) were subarachnoid hemorrhage (n = 14), cerebral infarction (n = 8), and traumatic brain injury (n = 3). RESULTS: There were no postoperative adverse events such as infection, bone resorption, implant exposure, or graft sinking in 24 patients during an average follow-up period of 19 months. One patient experienced acute epidural hemorrhage and required reoperation. CONCLUSION: This is the first report on the use of the ultra-high molecular-weight polyethylene Merlon shape. Our initial 4-year case series showed good outcomes with this method.


Assuntos
Lesões Encefálicas Traumáticas , Procedimentos de Cirurgia Plástica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Crânio/cirurgia , Polietilenos , Lesões Encefálicas Traumáticas/cirurgia
7.
J Neurol Surg A Cent Eur Neurosurg ; 84(5): 439-444, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35705179

RESUMO

BACKGROUND: Endoscopic hematoma evacuation is one of the most promising procedures for the treatment of intracerebral hemorrhage (ICH) to avoid severe outcomes, such as death or dependency. However, the effect of the procedure on the functional outcome remains controversial. Thus, standardization and sophistication are required to enhance the surgical results. This study aimed to evaluate the potential efficacy of ultrasonography (US) in endoscopic hematoma evacuation. METHODS: This study included 39 consecutive patients with spontaneous supratentorial ICH who underwent endoscopic hematoma evacuation between April 2019 and July 2021. The patients were divided into two groups, namely, surgery with or without US assistance. Rebleeding and evacuation rate were set as the primary endpoints, and operation time, requirement for repeat puncture, and modified Rankin scale at discharge were set as the secondary endpoints. During surgery, the burr hole was placed, and the dura mater was widely opened. The US probe was applied on the brain surface via the burr hole to detect the depth and direction of the hematoma cavity. With US assistance, the hematoma cavity was punctured with a cannula, and the transparent port was introduced into the hematoma cavity along the tract. The hematoma was gently evacuated with the irrigation-suction instrument. RESULTS: Of the 39 cases, 9 underwent endoscopic hematoma evacuation with US assistance. Rebleeding was noted in 0 and 2 (6.7%) patients with and without US assistance, respectively (p = 0.43). The mean hematoma evacuation rates were 78.6 and 80.6% in patients with and without US assistance, respectively (p = 0.80). In all cases with US assistance, the cavity could be reached with a single tap. However, repeat puncture was required in 20 (66.7%) cases without US assistance (p = 0.04). In one case, an unexpected residual hematoma was detected using US, which was applied after hematoma evacuation and before wound closure. The operation time was not extended even if US was used during the surgery. CONCLUSIONS: US-assisted hematoma evacuation is an effective procedure that can assist in the precise insertion of the puncture cannula and exclusion of the residual hematoma. US might contribute toward improving the accuracy of each step of the procedure, thus leading to better clinical outcomes.


Assuntos
Hemorragia Cerebral , Hematoma , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Hematoma/diagnóstico por imagem , Hematoma/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Ultrassonografia
8.
J Neurosurg Case Lessons ; 3(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36131567

RESUMO

BACKGROUND: Diagnosis of a microarteriovenous malformation (micro-AVM) is difficult, especially in the acute stage of rupture because of the small size of the nidus and the existence of hematoma. We report two cases of ruptured micro-AVMs detected by arterial spin labeling (ASL). OBSERVATIONS: In one case, a 45-year-old male was transported with a complaint of right hemiparesis. Computed tomography (CT) revealed a right parietal lobar hemorrhage. Standard magnetic resonance imaging (MRI) showed no abnormal findings as the cause of the hemorrhage. ASL 23 days after the onset demonstrated high signals on the medial wall of the hematoma. Digital subtraction angiography (DSA) showed a micro-AVM in accordance with the site of high signals on ASL. In another case, a 38-year-old female was transported with a complaint of left hemianopsia. CT on admission revealed a right parietal lobar hemorrhage. Standard MRI showed no abnormal findings as the cause of the hemorrhage. ASL 15 days after the onset demonstrated high signals on the internal wall of the hematoma. DSA showed micro-AVM in accordance with the site of high signaling on ASL. Both cases were successfully treated with open surgery. LESSONS: ASL can manifest micro-AVMs as high signals within the hematoma. ASL is a useful less-invasive screening tool for the detection of ruptured micro-AVMs.

9.
Asian J Endosc Surg ; 15(2): 415-426, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34954907

RESUMO

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every 2 years. In 2019, 291,792 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 15th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2018-2019.


Assuntos
Colecistectomia Laparoscópica , Laparoscopia , Cirurgiões , Humanos , Japão , Laparoscopia/métodos
10.
Sci Rep ; 11(1): 3132, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542452

RESUMO

Combination therapy of tegafur/uracil (UFT) and leucovorin (LV) is widely used to treat colorectal cancers. Although this therapy has a significant therapeutic effect, severe adverse effects occur frequently. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A useful assay that can quantitate plasma levels of 5-FU, uracil, and tegafur simultaneously for TDM has been desired, but such a method is not currently available. In this study, we aimed to develop a sensitive method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). After preparing plasma samples by protein precipitation and liquid extraction, 5-FU, uracil, and tegafur were analyzed by UPLC-MS/MS in negative electrospray ionization mode. Validation was performed according to US Food and Drugs Administration guidance. The calibration curves were linear over concentration ranges of 2-500 ng/mL for 5-FU, 20-5000 ng/mL for uracil, and 200-50,000 ng/mL for tegafur. The corresponding average recovery rates were 79.9, 80.9, and 87.8%. The method provides accuracy within 11.6% and precision below 13.3% for all three analytes. Matrix effects of 5-FU, uracil, and tegafur were higher than 43.5, 84.9, and 100.2%, respectively. This assay was successfully applied to assess the time courses of plasma 5-FU, uracil, and tegafur concentrations in two patients with colorectal liver metastasis who received UFT/LV therapy after hepatectomy. In conclusion, we succeeded to develop a sensitive and robust UPLC-MS/MS method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma. This method is potentially useful for TDM in patients receiving UFT/LV combination therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromatografia Líquida de Alta Pressão/normas , Monitoramento de Medicamentos/métodos , Fluoruracila/sangue , Espectrometria de Massas em Tandem/normas , Tegafur/sangue , Uracila/sangue , Antimetabólitos Antineoplásicos/sangue , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Humanos , Leucovorina/uso terapêutico , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos
11.
PLoS Genet ; 17(1): e1009113, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33476333

RESUMO

A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.


Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor de Morte Celular Programada 1/genética , Adenoma/imunologia , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Variações do Número de Cópias de DNA/genética , Feminino , Deriva Genética , Genoma Humano/genética , Humanos , Imunidade/genética , Imunidade/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Intervalo Livre de Progressão , Receptores de Antígenos de Linfócitos T/genética
12.
Nat Commun ; 12(1): 640, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510167

RESUMO

Neural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes like elevated oxidative stress. But how oxidative stress regulates NSPC and its neurogenic differentiation is less clear. Here we report that acutely elevated cellular oxidative stress in NSPCs modulates neurogenic differentiation through induction of Forkhead box protein O3 (FOXO3)-mediated cGAS/STING and type I interferon (IFN-I) responses. We show that oxidative stress activates FOXO3 and its transcriptional target glycine-N-methyltransferase (GNMT) whose upregulation triggers depletion of s-adenosylmethionine (SAM), a key co-substrate involved in methyl group transfer reactions. Mechanistically, we demonstrate that reduced intracellular SAM availability disrupts carboxymethylation and maturation of nuclear lamin, which induce cytosolic release of chromatin fragments and subsequent activation of the cGAS/STING-IFN-I cascade to suppress neurogenic differentiation. Together, our findings suggest the FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signaling cascade as a critical stress response program that regulates long-term regenerative potential.


Assuntos
Proteína Forkhead Box O3/metabolismo , Interferon Tipo I/metabolismo , Laminas/metabolismo , Estresse Oxidativo , Processamento de Proteína Pós-Traducional , Acetilcisteína/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Sequestradores de Radicais Livres/farmacologia , Glicina N-Metiltransferase/metabolismo , Células HEK293 , Herbicidas/farmacologia , Humanos , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Paraquat/farmacologia , S-Adenosilmetionina/metabolismo , Transdução de Sinais
13.
Anticancer Res ; 40(7): 3733-3742, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620612

RESUMO

BACKGROUND/AIM: Programmed death-ligand 1 (PD-L1/CD274) elicits T-cell anergy, leading to immune suppression. We aimed to determine the prognostic relevance of PD-L1 expression in the blood of breast cancer (BC) patients. MATERIALS AND METHODS: We measured PD-L1 mRNA expression in blood and tumor tissues of BC patients using RT-qPCR and a dataset from The Cancer Genome Atlas, and performed a survival analysis of PD-L1 expression in the blood of 330 BC patients. Flow cytometric analysis was performed using blood cells. RESULTS: No statistical difference in PD-L1 expression was seen between normal controls and BC in blood or tissues. There was a significant positive correlation between the PD-L1 expression levels in blood and tissues. Decreased PD-L1 expression in blood or tissues was associated with poor recurrence-free survival. PD-L1 is mainly expressed in polymorphonuclear leukocytes. CONCLUSION: Low expression of PD-L1 in the blood could serve as a biomarker of poor prognosis in BC patients.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Recidiva Local de Neoplasia/genética , RNA Mensageiro/genética , Idoso , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Recidiva Local de Neoplasia/patologia , Prognóstico
15.
BMC Cancer ; 20(1): 192, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143591

RESUMO

BACKGROUND: Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. However, few reports have investigated the association between dedifferentiation and glycosylation. Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation. METHODS: We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule. Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein ß-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans. RESULTS: Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones. Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components. Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis. CONCLUSION: Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Concanavalina A/metabolismo , Neoplasias Hepáticas/metabolismo , Lectinas de Ligação a Manose/metabolismo , Lectinas de Plantas/metabolismo , Idoso , Calystegia/química , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Glicosilação , Humanos , Imuno-Histoquímica/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , N-Acetilglucosaminiltransferases/metabolismo , Narcissus/química , Imagem Óptica/métodos , Polissacarídeos/química , Coloração e Rotulagem/métodos
16.
mSphere ; 5(2)2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161144

RESUMO

Surveillance of 10 hospitals and a regional public health laboratory in Myanmar identified 31 isolates of carbapenem-resistant Enterobacter cloacae complex harboring blaNDM-type Of these isolates, 19 were highly resistant to aminoglycosides and harbored one or more genes encoding 16S rRNA methylases, including armA, rmtB, rmtC, and/or rmtE Of the 19 isolates, 16 were Enterobacter xiangfangensis ST200, with armA on the chromosome and a plasmid harboring blaNDM-1 and rmtC, indicating that these isolates were clonally disseminated nationwide in Myanmar.IMPORTANCE The emergence of multidrug-resistant E. cloacae complex has become a public health threat worldwide. E. xiangfangensis is a recently classified species belonging to E. cloacae complex. Here, we report a clonal dissemination of multidrug-resistant E. xiangfangensis ST200 producing two types of New Delhi metallo-ß-lactamase (NDM-type MBL), NDM-1 and -4, and three types of 16S rRNA methylases, ArmA, RmtC, and RmtE, in hospitals in Myanmar. The observation of these multidrug-resistant E. xiangfangensis ST200 isolates stresses the urgency to continue molecular epidemiological surveillance of these pathogens in Myanmar and in South Asian countries.


Assuntos
Aminoglicosídeos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Enterobacter cloacae/efeitos dos fármacos , Metiltransferases/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Enterobacter/efeitos dos fármacos , Enterobacter/genética , Enterobacter cloacae/enzimologia , Enterobacter cloacae/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Mianmar/epidemiologia , Filogenia , RNA Ribossômico 16S/genética
17.
Cancer Sci ; 111(4): 1039-1046, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31957175

RESUMO

Cancer is a leading cause of death worldwide, and the incidence continues to increase. Despite major research aimed at discovering and developing novel and effective anticancer drugs, oncology drug development is a lengthy and costly process, with high attrition rates. Drug repositioning (DR, also referred to as drug repurposing), the process of finding new uses for approved noncancer drugs, has been gaining popularity in the past decade. DR has become a powerful alternative strategy for discovering and developing novel anticancer drug candidates from the existing approved drug space. Indeed, the availability of several large established libraries of clinical drugs and rapid advances in disease biology, genomics/transcriptomics/proteomics and bioinformatics has accelerated the pace of activity-based, literature-based and in silico DR, thereby improving safety and reducing costs. However, DR still faces financial obstacles in clinical trials, which could limit its practical use in the clinic. Here, we provide a brief review of DR in cancer and discuss difficulties in the development of DR for clinical use. Furthermore, we introduce some promising DR candidates for anticancer therapy in Japan.


Assuntos
Antineoplásicos/uso terapêutico , Descoberta de Drogas , Reposicionamento de Medicamentos , Neoplasias/tratamento farmacológico , Biologia Computacional , Humanos , Japão , Neoplasias/epidemiologia
18.
Asian J Endosc Surg ; 13(1): 7-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31828925

RESUMO

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every two years to evaluate the status of endoscopic surgery over time. In 2017, 248 743 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 14th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2016-2017.


Assuntos
Endoscopia/métodos , Endoscopia/estatística & dados numéricos , Endoscopia/efeitos adversos , Endoscopia/educação , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Humanos , Japão/epidemiologia , Sociedades Médicas/estatística & dados numéricos
19.
Cancer Chemother Pharmacol ; 85(2): 345-352, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31605153

RESUMO

BACKGROUND: Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired drug clearance during liver regeneration. We investigated the pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil (5-FU) during liver regeneration after major hepatectomy in a rat model. METHODS: Thirty-six male Wistar rats were divided into control (C), control with chemotherapy (CC), hepatectomy (H), and hepatectomy with chemotherapy (HC) groups. The CC and HC groups were administered 5-FU for 4 days. Plasma 5-FU, liver weight, and liver dihydropyrimidine dehydrogenase (DPD) were measured. The ileal villous height was measured to determine adverse effects. RESULTS: The area under the curve and maximum plasma concentration of 5-FU increased by up to 51% and 32%, respectively, in the HC group compared to the CC group. The liver regeneration rate was significantly lower in the HC group than in the H group (67.3 ± 7.4 vs 33.0 ± 5.7%, p < 0.001). The HC group had a significantly lower liver DPD than the CC group (4.4 ± 1.1 mg vs 6.9 ± 1.1 mg, p < 0.01). The HC group had a significantly lower ileal villous height than the CC group (253 ± 40 µm vs. 318 ± 36 µm, p < 0.05). CONCLUSIONS: Reduction of the total liver DPD following major hepatectomy caused increased plasma 5-FU levels and 5-FU-associated toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Fluoruracila/farmacocinética , Fluoruracila/toxicidade , Fígado/efeitos dos fármacos , Animais , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Modelos Animais de Doenças , Feminino , Hepatectomia/métodos , Fígado/metabolismo , Regeneração Hepática/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
20.
Asian J Endosc Surg ; 12(1): 7-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30681279

RESUMO

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, the operative procedure has been standardized, and the safety and usefulness of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less-invasive surgery, the number of endoscopic procedures has been increasing in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. For example, JSES established a technical skills certification system for surgeons to train instructors how to teach safe endoscopic surgery, and the organization performs a national survey every 2 years. In 2015, a total of 211 953 patients underwent endoscopic surgery in all surgical domains, including abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The course of laparoscopic surgery's development and its current status are reported here based on the results of the most recent questionnaire survey conducted by JSES.


Assuntos
Endoscopia/estatística & dados numéricos , Complicações Intraoperatórias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Endoscopia/efeitos adversos , Humanos , Japão , Seleção de Pacientes , Utilização de Procedimentos e Técnicas , Inquéritos e Questionários
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