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A 79-year-old man visited a hospital for right upper abdominal pain and nausea. After conservative treatment for cholangitis and pancreatitis owing to a pancreatic head lesion, he was referred to our hospital for further evaluation and treatment of the lesion. He was diagnosed with pancreatic head cancer or carcinoma of papilla of Vater and underwent subtotal stomach- preserving pancreaticoduodenectomy. Postoperative histopathological examination revealed the coexistence of adenocarcinoma( 60%)and neuroendocrine carcinoma(40%)components, consistent with the diagnosis of mixed neuroendocrine- non-neuroendocrine neoplasm(MiNEN). In addition, regional lymph node metastasis of the adenocarcinoma component was found. Adjuvant chemotherapy was not administered because of a poor performance status. Lung metastasis occurred 13 months after surgery. Chemotherapy with S-1 was administered, and partial response was obtained 17 months after surgery. Herein, we report this rare case of MiNEN of the papilla of Vater with lung metastasis.
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Adenocarcinoma , Ampola Hepatopancreática , Neoplasias Pulmonares , Neoplasias Pancreáticas , Masculino , Humanos , Idoso , Ampola Hepatopancreática/cirurgia , Ampola Hepatopancreática/patologia , Pancreaticoduodenectomia , Adenocarcinoma/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pancreáticas/cirurgia , Pulmão/cirurgiaRESUMO
A 53-year-old woman was admitted to our hospital because of hepatic dysfunction found during a medical checkup. Cholecystitis was suspected, and unenhanced computed tomography (CT) was initially performed because she had bronchial asthma. However, a tumor-like lesion was seen at the bottom of the gallbladder. Contrast-enhanced CT was performed 3 weeks later, and the tumor-like lesion was enhanced and had increased in size. Endoscopic ultrasound fine-needle aspiration did not reveal any signs of malignancy. Colonoscopy revealed ulcerations in the transverse colon, and invasion from gallbladder cancer was suspected. Our preoperative diagnosis was xanthogranulomatous cholecystitis, but gallbladder cancer could not be excluded. Gallbladder bed resection and partial resection of the transverse colon were performed. Intraoperative frozen section analysis did not reveal any malignant findings; hence, we considered that lymph node dissection was unnecessary. Pathological examination confirmed xanthogranulomatous cholecystitis with abscess formation. In cases of surgery for xanthogranulomatous cholecystitis, it is important to consider that this condition could coexist with gallbladder cancer.
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Colecistite , Colo Transverso , Neoplasias da Vesícula Biliar , Colecistite/cirurgia , Feminino , Vesícula Biliar , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Granuloma/diagnóstico por imagem , Granuloma/cirurgia , Humanos , Pessoa de Meia-Idade , XantomatoseRESUMO
PURPOSE: One function of the blood-brain barrier (BBB) is the efflux of xenobiotics by breast cancer resistance protein (BCRP), and inhibition of BCRP can cause unexpected central nervous system toxicity. Despite the importance of BCRP inhibition and the associated risk of BBB penetration in vivo, there has been little investigation of it to date. In this study, inhibition of BCRP-mediated transport was assessed by in vitro assay in the presence of bovine serum albumin (BSA) to change the unbound inhibitor concentrations, and the in vitro-in vivo correlation (IVIVC) at the BBB was evaluated. METHODS AND RESULTS: The IC50 values of BCRP inhibitors were determined in vitro with and without BSA and the inhibitors were categorized into two groups. One group of compounds had little risk of inhibiting BCRP because of their low unbound concentrations. In contrast, the other group has the potential to facilitate BBB penetration by inhibiting BCRP. In the IVIVC approach, brain concentrations and the brain-to-plasma ratio were better correlated with the ratio of the unbound plasma concentration at steady-state to the unbound-fraction-adjusted IC50. CONCLUSION: We have found a way to obtain a better in vitro-in vivo correlation for BCRP-mediated transport.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Barreira Hematoencefálica/metabolismo , Xenobióticos/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Cães , Concentração Inibidora 50 , Células Madin Darby de Rim Canino , Masculino , Camundongos , PermeabilidadeRESUMO
The patient was a 41-year-old woman. When she was 39 years old, she had undergone laparoscopic high anterior resection for sigmoid colon cancer without adjuvant chemotherapy. Histologically, the surgical specimen was type 2, tub2, pT4a (SE), pN0, int, INF b, ly1, v1, and pStage II. Nine months after the operation, she suffered from abdominal fullness. Laborato- rydata showed elevation of tumor markers: the CEA level was 6.48 ng/mL, the CA19-9 level was 89.70 U/mL, and the CA125 level was 662 U/mL. Computed tomographyrevealed bilateral ovarian tumors and lung and peritoneal nodules with massive ascites. Chemotherapywas started with a regimen consisting of capecitabine plus oxaliplatin(CapeOX)that included bevacizumab. After 4 courses, the sizes of the lung and peritoneal nodules had decreased and the amount of ascites was almost zero. However, the ovarian tumors had increased in size and her sense of abdominal fullness had not improved. Bilateral oophorectomy with hysterectomy was performed to alleviate her symptom. Immunohistochemically, the resected ovarian tumors were negative for cytokeratin 7 and positive for cytokeratin 20. CapeOX with bevacizumab was then resumed. However, the lung tumor had graduallyincreased in size, and therefore, she underwent partial resection of the lung for the metastatic lung tumor.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias do Colo Sigmoide/tratamento farmacológico , Adulto , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Colectomia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/secundário , Oxaliplatina , Pneumonectomia , Neoplasias do Colo Sigmoide/patologia , Neoplasias do Colo Sigmoide/cirurgiaRESUMO
Gallbladder (GB) perforation is a very rare posttraumatic abdominal injury. It is potentially life-threatening, and good outcome requires early diagnosis. We present a case of isolated posttraumatic GB perforation in which the precise sonographic (US) diagnosis led us to apply proper management. Color Doppler US showed a clear to-and-fro flow signal passing through the perforation site, and contrast-enhanced US confirmed the presence of a small defect in the GB wall. When examining posttraumatic patients, the possibility of GB perforation must be kept in mind. Color Doppler US and contrast-enhanced US are the examinations of choice to detect the perforation site and show bile movement through the perforation.
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Meios de Contraste , Doenças da Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/lesões , Ferimentos não Penetrantes/diagnóstico por imagem , Acidentes por Quedas , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Compostos Férricos , Vesícula Biliar/cirurgia , Doenças da Vesícula Biliar/cirurgia , Humanos , Aumento da Imagem/métodos , Ferro , Óxidos , Ultrassonografia Doppler em Cores/métodos , Ferimentos não Penetrantes/cirurgiaRESUMO
BACKGROUND: Advancements in technology have overcome geographical barriers, making telemedicine, which offers remote emergency services, healthcare, and medication guidance, increasingly popular. COVID-19 restrictions amplified its global importance by bridging distances. OBJECTIVE: This study aimed to analyze Chinese and global literature data, present new global telemedicine research trends, and clarify the development potential, collaborations, and deficiencies in China's telemedicine research. METHODS: We conducted bibliometrics and network analyses on relevant documents from the Web of Science database from 2001 to 2022. Data collection was completed on October 30, 2023. Considering COVID-19's impact, 2020 was used as a baseline, dividing the data into 2 periods: 2001-2019 and 2020-2022. The development potential was determined based on publication trends. An international coauthorship network analysis identified collaboration statuses and potential. Co-occurrence analysis was conducted for China and the world. RESULTS: We identified 25,333 telemedicine-related research papers published between 2001 and 2022, with a substantial increase during the COVID-19 period (2020-2022), particularly in China (1.93-fold increase), moving its global publication rank from tenth to sixth. The United States, the United Kingdom, and Australia contributed 62.96% of the literature, far ahead of China's 3.90%. Globally, telemedicine research increased significantly post-2020. Between 2001 and 2019, the United States and Australia were central in coauthor networks; post-2020, the United States remained the largest node. Network hubs included the United States, the United Kingdom, Australia, and Canada. Keyword co-occurrence analysis revealed 5 global clusters from 2001 to 2019 (system technology, health care applications, mobile health, mental health, and electronic health) and 2020 to 2022 (COVID-19, children's mental health, artificial intelligence, digital health, and rehabilitation of middle-aged and older adults). In China, the research trends aligned with global patterns, with rapid growth post-2020. From 2001 to 2019, China cooperated closely with Indonesia, India, Japan, Taiwan, and South Korea. From 2020 to 2022, cooperation expanded to Japan, Singapore, Malaysia, and South Korea, as well as Saudi Arabia, Egypt, South Africa, Ghana, Lebanon, and other African and Middle Eastern countries. Chinese keyword co-occurrence analysis showed focus areas in system technology, health care applications, mobile health, big data analysis, and electronic health (2001-2019) and COVID-19, artificial intelligence, digital health, and mental health (2020-2022). Although psychology research increased, studies on children's mental health and middle-aged and older adults' rehabilitation were limited. CONCLUSIONS: We identified the latest trends in telemedicine research, demonstrating its significant potential in China and providing directions for future development and collaborations in telemedicine research.
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This study conducted policy and regulation analyses and user acceptance surveys in three East Asian countries with developed telecommunication infrastructure (China, South Korea, and Japan) to determine the most effective way to implement mobile health (mHealth). Regional differences in users' emphasis on the purpose of mHealth, including medical information referral or health management, appear to be influenced by regional regulation, thus making regulation analysis important when considering mHealth penetration strategies. Potential mHealth users have high expectations for medical information and correspondence, which is crucial for the pharmaceutical industry in terms of providing information and retaining patients. Furthermore, potential users are willing to use the system medically, which is beneficial to the pharmaceutical industry when introducing mHealth and prescriptions in combination.
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The 14th Japan Bioanalysis Forum Symposium was held at Tower Hall Funabori, Japan from 1-3 March 2023. The conference theme, 'Bringing Together - the Expertise of Bioanalysis', aimed to enable people from various fields to gather, learn and collaborate together for the common goal of delivering medicines to patients faster. Approximately 360 participants from various fields, including pharmaceutical industries, contractors, academia and regulatory authorities, gathered at an in-person symposium which had an online participation option, for the first time in 4 years. The symposium offered a wide range of topics including ICH M10, new modalities, biomarkers, immunogenicity, electronization and patient-centric sampling. The latest research results were provided from domestic and overseas scientists. This report summarizes the major topics.
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Relatório de Pesquisa , Humanos , Japão , BiomarcadoresRESUMO
(1) Background: Contact tracing and notification apps for coronavirus disease 2019 (COVID-19) are installed on smartphones and are intended to detect contact with another person's device. A high installation rate is important for these apps to enable them to be effective countermeasures against the silent transmission of diseases. However, the installation rate varies among apps and regions and the penetration dynamics of these applications are unclear. (2) Methods: The download behavior of contact tracing applications was investigated using publicly available datasets. The increase in downloads was modeled using a system dynamics model derived from the product growth model. (3) Results: The imitation effects present in the traditional product growth model were not observed in COVID-19 contact tracing apps. The system dynamics model, without the imitation effect, identified the downloads of the Australian COVIDSafe app. The system dynamics model, with a layered adopter, identified the downloads of the Japanese tracing app COCOA. The spread of COVID-19 and overall anti-COVID-19 government intervention measures in response to the spread of infection seemed to result in an increase in downloads. (4) Discussion: The suggested layered structure of users implied that individualized promotion for each layer was important. Addressing the issues among users who are skeptical about adoption is pertinent for optimal penetration of the apps.
Assuntos
COVID-19 , Aplicativos Móveis , Telemedicina , Austrália , COVID-19/epidemiologia , COVID-19/prevenção & controle , Busca de Comunicante , Humanos , SARS-CoV-2RESUMO
Waste management workers experience high stress and physical strain in their work environment, but very little empirical evidence supports effective health management practices for waste management workers. Hence, this study investigated the effects of worker characteristics and biometric indices on workers' physical and psychological loads during waste-handling operations. A biometric measurement system was installed in an industrial waste management facility in Japan to understand the actual working conditions of 29 workers in the facility. It comprised sensing wear for data collection and biometric sensors to measure heart rate (HR) and physical activity (PA) based on electrocardiogram signals. Multiple regression analysis was performed to evaluate significant relationships between the parameters. Although stress level is indicated by the ratio of low frequency (LF) to high frequency (HF) or high LF power in HR, the results showed that compared with workers who did not handle waste, those who did had lower PA and body surface temperature, higher stress, and lower HR variability parameters associated with higher psychological load. There were no significant differences in HR, heart rate interval (RRI), and workload. The psychological load of workers dealing directly with waste was high, regardless of their PA, whereas others had a low psychological load even with high PA. These findings suggest the need to promote sustainable work relationships and a quantitative understanding of harsh working conditions to improve work quality and reduce health hazards.
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Saúde Ocupacional , Gerenciamento de Resíduos , Humanos , Estudos Transversais , Carga de Trabalho , Frequência Cardíaca/fisiologia , Exercício FísicoRESUMO
Analyzing unstable small molecule drugs and metabolites in blood continues to be challenging for bioanalysis. Although scientific countermeasures such as immediate cooling, immediate freezing, addition of enzyme inhibitors, pH adjustment, dried blood spot or derivatization have been developed, selecting the best practices has become an issue in the pharmaceutical industry as the number of drugs with such problems is increasing, even for generic drugs. In this study, we conducted a comprehensive literature review and a questionnaire survey to determine a suitable practice for evaluating instability and implementing countermeasures. Three areas of focus, matrix selection, effect of hemolysis and selection of esterase inhibitors, are discussed.
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Bioensaio/métodos , Química Analítica/normas , Humanos , Japão , Inquéritos e QuestionáriosRESUMO
Approximately 280 people from pharmaceutical industries, contractors, academic institutions and regulatory authorities attended the 13th Japan Bioanalysis Forum Symposium. The symposium was held via web to prevent the spread of COVID-19 from the 28 February to 2 March 2022. The theme of the symposium was 'All for One Goal', and the event has provided an opportunity for open discussion among researchers with different backgrounds but who share a common goal: "to deliver more effective and safe pharmaceuticals to patients as quickly as possible". The speakers focused on hot topics in bioanalysis, including chromatography, biomarker analysis, cell and gene therapy, COVID-19 and antidrug antibody. This symposium provided a great opportunity for the participants to have meaningful discussions, even though 'on the web' was a limited space.
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COVID-19 , Humanos , Japão , Anticorpos , Indústria FarmacêuticaRESUMO
A sensitive high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for measuring vinorelbine was developed. A 100 µL aliquot of plasma was spiked with deuterium-labeled internal standard and subjected to solid-phase extraction using an Oasis HLB µ-elution plate. Two microliters of the extracted samples was directly injected into LC/MS/MS. Chromatographic separation was achieved on a Capcell Pak C18 UG column (2 × 75 mm) with a gradient elution of methanol (mobile phase B) against 0.05% formic acid in aqueous 10 mm ammonium formate (mobile phase A). The LC flow rate was set to 0.28 mL/min and the gradient (solvent B concentration) was processed from 40 to 90%. In mass spectrometric detection, observation of the reaction from a double-charged precursor ion [M + 2H](2+) (m/z 390) to product ion m/z 122 provided very high sensitivity. The method was validated with a lower limit of detection of 0.2 ng/mL with 0.1 mL of plasma, and the method was used to determine the plasma pharmacokinetics of vinorelbine in dogs.
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Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Vimblastina/análogos & derivados , Adsorção , Animais , Área Sob a Curva , Cães , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray , Vimblastina/sangue , Vimblastina/farmacocinética , VinorelbinaRESUMO
(1) Background: During the global spread of COVID-19, Japan has been among the top countries to maintain a relatively low number of infections, despite implementing limited institutional interventions and its high population density. This study investigated how limited intervention policies have affected public health and economic conditions in the COVID-19 context and aimed to gain insight into the effective and sustainable measures against new infectious diseases in densely inhabited areas. (2) Methods: A system dynamics approach was employed. Qualitative causal loop analysis and stock and quantitative flow model analysis were performed, using a Tokyo Metropolitan area dataset. (3) Results: A causal loop analysis suggested that there were risks in prematurely terminating such interventions. Based on this result and the subsequent quantitative modeling, we found that the short-term effectiveness of a short-term pre-emptive stay-at-home request caused a resurgence in the number of positive cases, whereas an additional request provided a limited negative add-on effect for economic measures (e.g., number of electronic word-of-mouth communications and restaurant visits). (4) Conclusions: These findings suggest the superiority of a mild and continuous intervention as a long-term countermeasure under epidemic pressures when compared with strong intermittent interventions.
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In Japan's response to the coronavirus disease 2019 (COVID-19), virus testing was limited to symptomatic patients due to limited capacity, resulting in uncertainty regarding the spread of infection and the appropriateness of countermeasures. System dynamic modelling, comprised of stock flow and infection modelling, was used to describe regional population dynamics and estimate assumed region-specific transmission rates. The estimated regional transmission rates were then mapped against actual patient data throughout the course of the interventions. This modelling, together with simulation studies, demonstrated the effectiveness of inbound traveler quarantine and resident self-isolation policies and practices. A causal loop approach was taken to link societal factors to infection control measures. This causal loop modelling suggested that the only effective measure against COVID-19 transmission in the Japanese context was intervention in the early stages of the outbreak by national and regional governments, and no social self-strengthening dynamics were demonstrated. These findings may contribute to an understanding of how social resilience to future infectious disease threats can be developed.
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Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , COVID-19 , Infecções por Coronavirus/transmissão , Humanos , Japão , Modelos Teóricos , Pneumonia Viral/transmissão , Quarentena , SARS-CoV-2 , Isolamento SocialRESUMO
We present a case of gallbladder hernia into the foramen of Winslow. During the diagnosis of hernia, ultrasonography, computed tomography and intravenous computed tomography, cholangiography of the abdomen were performed. Ultrasonography detected gallstone, but did not provide sufficient information to diagnose gallbladder hernia. Computed tomography yielded the correct diagnosis. At laparoscopic cholecystectomy, the diagnosis was confirmed.
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Doenças da Vesícula Biliar/diagnóstico por imagem , Hérnia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Colecistectomia Laparoscópica , Meios de Contraste , Diagnóstico Diferencial , Feminino , Doenças da Vesícula Biliar/cirurgia , Herniorrafia , Humanos , PeritônioRESUMO
Applicability of atmospheric pressure photoionization mass spectrometry (APPI-MS) to the analysis of hydrophilic drugs was investigated. Model compounds with moderate to high hydrophilicity was tested, and most compounds showed good signal response with APPI-MS, but some compounds with high molecular polarity like folic acid derivatives, glycoside and some nucleic acid derivatives showed very weak signal responses. By observing relationship between the compounds' physicochemical properties and APPI response, compounds with higher lipophilicity and less polar surface area were considered to be advantageous for APPI-MS. To provide information for applying APPI-MS to the analysis of hydrophilic drugs, approximate lower limit of calculated octanol-water partition coefficient and the higher limit of the number of oxygen and nitrogen atoms were determined to be -0.95 and 6, respectively. These APPI-applicable model compounds could be analyzed by reversed-phase high performance liquid chromatography-APPI-tandem mass spectrometry.
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Preparações Farmacêuticas/análise , Espectrometria de Massas em Tandem/métodos , Pressão Atmosférica , Interações Hidrofóbicas e Hidrofílicas , Oxigênio , Preparações Farmacêuticas/química , Processos Fotoquímicos , Espectrometria de Massas em Tandem/instrumentaçãoRESUMO
AIM: Tacrolimus (TAC) is an important drug for inflammatory diseases. However, TAC has several limitations, such as variable trough concentrations among individuals and a high medication frequency. In this study, we created NK61060, a novel micellar TAC formulation, to circumvent these disadvantages. MATERIALS & METHODS: Immunosuppressive activity of NK61060 was determined in the collagen-induced arthritis rat model, mannan-induced arthritis mouse model and dextran sodium sulfate-induced colitis mouse model. The pharmacokinetics and toxicology of NK61060 were evaluated in those models. RESULTS: In arthritis and colitis models, NK61060 exhibited superior immunosuppressive activity compared with that of TAC. Pharmacokinetic and toxicological analyses indicated that NK61060 had a wider safety margin and could be administered at a reduced medication frequency. CONCLUSION: NK61060 mitigates the trough concentration variability and the medication frequency and it may be a safer and more effective option for use in clinical settings. Further studies are needed to determine its clinical usefulness.
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Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos/química , Imunossupressores/administração & dosagem , Tacrolimo/administração & dosagem , Animais , Área Sob a Curva , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colágeno/imunologia , Sulfato de Dextrana/toxicidade , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Mananas/imunologia , Camundongos , Camundongos Endogâmicos ICR , Micelas , Polietilenoglicóis/química , Ratos , Ratos Sprague-DawleyRESUMO
We present a case of liver metastasis from an uterine leiomyosarcoma in which contrast-enhanced ultrasonography (CEUS) helped determine the bleeding point and prevented a delay in devising diagnostic and therapeutic strategies. CEUS allowed us to differentiate active from nonactive bleeding on the basis of presence or absence of contrast extravasation in the ascites. CEUS is the first examination performed when liver tumor rupture is suspected. Reference to the preangiographic CEUS results is expected to provide a road map for angiography.