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1.
Int J Comput Assist Radiol Surg ; 18(1): 1-8, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35922706

RESUMO

PURPOSE: Gastrointestinal cancer can be treated using a flexible endoscope through a natural orifice. However, treatment instruments with limited degrees of freedom (DOFs) require a highly skilled operator. Articulated devices useful for endoluminal procedures, such as endoscopic submucosal dissection and biopsy, have been developed. These devices enable dexterous operation in a narrow lumen; however, they suffer from limitations such as large size and high cost. To overcome these limitations, we developed a 2.5-mm articulated forceps that can be inserted into a standard endoscope channel based on a compliant mechanism. METHODS: The compliant mechanism allows the device to be compact and affordable, which is possible due to its monolithic structure. The proposed mechanism consists of two segments, 1-DOF grasping and 2-DOF bending, that are actuated by tendon-sheath mechanisms. A prototype was designed based on finite element analysis results. RESULTS: To confirm the effectiveness of the proposed mechanism, we fabricated the prototype using a 3D printer. A series of mechanical performance tests on the prototype revealed that it achieved the following specifications: (1) DOF: 1-DOF grasping + 2-DOF bending, (2) outer diameter: 2.5 mm, (3) length of the bending segment: 30 mm, and (4) range of motion: [Formula: see text] to [Formula: see text] (grasping) and [Formula: see text] to [Formula: see text] (bending). Finally, we performed a tissue manipulation test on an excised porcine colon and found that a piece of mucous membrane tissue was successfully resected using an electric knife while being lifted with the developed forceps. CONCLUSION: The results of the evaluation experiment demonstrated a positive feasibility of the proposed mechanism, which has a simpler structure compared to those of other conventional mechanisms; furthermore, it is potentially more cost-effective and is disposable. The mechanical design, prototype implementation, and evaluations are reported in this paper.


Assuntos
Endoscópios , Procedimentos Cirúrgicos Robóticos , Animais , Suínos , Desenho de Equipamento , Procedimentos Cirúrgicos Robóticos/métodos , Biópsia , Instrumentos Cirúrgicos
2.
Disaster Med Public Health Prep ; 17: e78, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35129102

RESUMO

OBJECTIVE: Based on experiences following the Great East Japan Earthquake and nuclear power plant accident in 2011, Nuclear Emergency Core Hospitals (NECHs) were designated as centers for radiation disaster management in Japan. This study aimed to investigate their current status and identify areas for improvement. METHODS: This cross-sectional study was conducted in October 2018. Demographic data were collected by a questionnaire with free text responses about attitudes toward NECHs. Considerations regarding risk communications during a radiation disaster were analyzed using qualitative text mining analysis. RESULTS: A total of 36 hospitals participated in this study. Only 31% of NECHs anticipated a radiation disaster. The importance of business continuity plans and risk communications was shown. Text analysis identified 7 important categories for health care workers during a radiation disaster, including media response, communications to hospital staff, risk communications, radiation effects on children, planning for a radiation disaster in the region, rumors, and the role in the region. CONCLUSION: The radiation disaster medical system and NECHs in Japan were surveyed. The importance of risk communications, planning for a radiation disaster in each region, and the role in the region are identified as issues that need to be addressed.


Assuntos
Planejamento em Desastres , Acidente Nuclear de Fukushima , Criança , Humanos , Japão , Estudos Transversais , Hospitais , Inquéritos e Questionários , Centrais Nucleares
3.
Antioxid Redox Signal ; 36(1-3): 172-184, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34015957

RESUMO

Significance:In vivo molecular and metabolic imaging is an emerging field in biomedical research that aims to perform noninvasive detection of tissue metabolism in disease states and responses to therapeutic agents. The imbalance in tissue oxidation/reduction (Redox) states is related to the onset and progression of several diseases. Tissue redox metabolism provides biomarkers for early diagnosis and drug treatments. Thus, noninvasive imaging of redox metabolism could be a useful, novel diagnostic tool for diagnosis of redox-related disease and drug discovery. Recent Advances:In vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) is a technique that enables the imaging of free radicals in living animals. DNP enhances the MRI signal by irradiating the target tissue or solution with the free radical molecule's electron paramagnetic resonance frequency before executing pulse sequence of the MRI. In vivo DNP-MRI with redox-sensitive nitroxyl radicals as the DNP redox contrast agent enables the imaging of the redox metabolism on various diseases. Moreover, nitroxyl radicals show antioxidant effects that suppress oxidative stress. Critical Issues: To date, considerable progress has been documented preclinically in the development of animal imaging systems. Here, we review redox imaging of in vivo DNP-MRI with a focus on the recent progress of this system and its uses in patients with redox-related diseases. Future Directions: This technique could have broad applications in the study of other redox-related diseases, such as cancer, inflammation, and neurological disorders, and facilitate the evaluation of treatment response as a theranostic tool. Antioxid. Redox Signal. 36, 172-184.


Assuntos
Imageamento por Ressonância Magnética , Medicina de Precisão , Animais , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Radicais Livres , Humanos , Imageamento por Ressonância Magnética/métodos , Oxirredução
4.
World J Gastrointest Oncol ; 13(8): 822-834, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34457188

RESUMO

This review report represents an overview of research and development on medical hyperspectral imaging technology and its applications. Spectral imaging technology is attracting attention as a new imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. Considering the recent advances in imaging, this technology provides an opportunity for two-dimensional mapping of oxygen saturation (SatO2) of blood with high accuracy, spatial spectral imaging, and its analysis and provides detection and diagnostic information about the tissue physiology and morphology. Multispectral imaging also provides information about tissue oxygenation, perfusion, and potential function during surgery. Analytical algorithm has been examined, and indication of accurate map of relative hemoglobin concentration and SatO2 can be indicated with preferable resolution and frame rate. This technology is expected to provide promising biomedical information in practical use. Several studies suggested that blood flow and SatO2 are associated with gastrointestinal disorders, particularly malignant tumor conditions. The use and analysis of spectroscopic images are expected to potentially play a role in the detection and diagnosis of these diseases.

5.
Medicine (Baltimore) ; 100(8): e24929, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663129

RESUMO

INTRODUCTION: Fat embolism syndrome (FES) is a known complication of long bone fracture and can affect multiple organs. The organ most commonly affected with FES is the lung. Severe cases of FES from long bone fracture can cause acute respiratory distress syndrome (ARDS). Although the treatment of ARDS remains challenging, it is reported that a lung protection strategy and prone positioning are effective. In addition, early fixation is reported to be beneficial in respiratory failure due to FES, though it may exacerbate respiratory failure during the perioperative period. We report the use of venovenous extracorporeal membrane oxygenation (VV-ECMO) for the successful perioperative management of a patient diagnosed with ARDS due to FES. PATIENT CONCERNS: A 24-year-old man injured in a traffic accident was brought to our emergency department due to shock and consciousness disorder. DIAGNOSIS: After examining the patient, we noted bilateral pneumothorax, liver and spleen injuries, and multiple long bone fractures. Four days after admission, he was diagnosed with FES due to a prolonged consciousness disorder, progressive hypoxia with diffuse lung damage, and cutaneous and mucosal petechiae. INTERVENTION: As respiratory failure progressed, VV-ECMO was initiated on the 6th day. To improve the respiratory failure caused by ARDS, prone position therapy was necessary. Thus, we performed osteosynthesis on the 9th day under ECMO. Prone position therapy was started after surgery. OUTCOMES: Subsequently, his respiratory condition and chest radiographs improved steadily. VV-ECMO was discontinued on the 17th day and the ventilator was removed on the 28th day. His consciousness levels improved without residual central nervous system complications. CONCLUSION: Our study reveals the successful improvement of FES-induced ARDS by osteosynthesis and prone positioning under VV-ECMO. This strategy prioritizes supportive treatment over pharmacologic interventions.


Assuntos
Embolia Gordurosa/etiologia , Oxigenação por Membrana Extracorpórea/métodos , Fraturas do Fêmur/complicações , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Acidentes de Trânsito , Fraturas do Fêmur/cirurgia , Humanos , Masculino , Decúbito Ventral , Adulto Jovem
6.
Surg Laparosc Endosc Percutan Tech ; 31(6): 778-781, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33734210

RESUMO

BACKGROUND: In laparoscopic gastrointestinal surgery, the location of the tumor is identified mainly with marking methods, such as ink tattooing and intraoperative gastrointestinal endoscopy and marking with a metal clip followed by confirmation with intraoperative x-ray fluoroscopy. Each method has disadvantages, such as complexity, instability of ink sticks, and radiation exposure. Thus, a simple and less-invasive marking method is needed. METHODS: We developed a wireless light-emitting marker with a miniature light-emitting diode that uses a magnetic field resonance mechanism. It emits 4 individual colors-red, blue, green, and white. We confirmed the usefulness of this marker system in ex vivo and in vivo animal experiments. RESULTS: In the ex vivo experiment in porcine intestines, use of the wireless marker was successful, as each color of emitted light was recognized from outside the intestine. In the live animal experiment, it was confirmed that the light emitted by the marker system was visible in the porcine intestinal tract during laparoscopic surgery. The light emitted by the wireless marker in the intestinal tract was confirmed with a laparoscope in a simulated animal surgery. CONCLUSION: We have developed an innovative, radiation-free and reliable light-emitting marker system that uses a magnetic field resonance mechanism that emits four colors of light during laparoscopic surgery.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Laparoscopia , Tatuagem , Animais , Trato Gastrointestinal , Campos Magnéticos , Suínos
7.
Liver Transpl ; 27(6): 840-853, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33259137

RESUMO

Hepatic ischemia/reperfusion injury (IRI) is a major complication of liver surgery and transplantation, especially in patients with nonalcoholic steatohepatitis (NASH). The mechanism of NASH susceptibility to IRI has not been fully clarified. We investigated the role of liver-produced histidine-rich glycoprotein (HRG) in NASH IRI. A NASH mouse model was established using C57BL/6J mice fed a methionine-choline-deficient diet (MCDD) for 6 weeks. The MCDD and standard diet groups were exposed to 60 minutes of partial hepatic ischemia/reperfusion (I/R). We further evaluated the impact of HRG in this context using HRG knockdown (KD) mice. IRI increased HRG expression in the standard diet group, but not in the MCDD group after I/R. HRG expression was inversely correlated with neutrophil infiltration and the formation of neutrophil extracellular traps (NETs). HRG KD mice showed severe liver injury with neutrophil infiltration and the formation of NETs. Pretreatment with supplementary HRG protected against I/R with the inhibition of neutrophil infiltration and the formation of NETs. In vitro, hepatocytes showed that the expression of HRG was upregulated under hypoxia/reoxygenation conditions, but not in response to oleic acid-treated hepatocytes. The decrease in HRG expression in fatty hepatocytes was accompanied by decreased farnesoid X receptor and hypoxia inducible factor 2 alpha subunit expression. HRG is a hepatoprotective factor during hepatic IRI because it decreases neutrophil infiltration and the formation of NETs. The decrease in HRG is a cause of susceptibility to IRI in steatotic livers. Therefore, HRG is a new therapeutic target for minimizing liver damage in patients with NASH.


Assuntos
Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Traumatismo por Reperfusão , Animais , Humanos , Isquemia , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Proteínas , Traumatismo por Reperfusão/prevenção & controle
8.
Stem Cell Res Ther ; 11(1): 508, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246503

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. METHODS: Male C57BL/6 N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection. RESULTS: The administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, the expression of miR-126 was increased in exosomes from histone-exposed ADSCs. Remarkably, the inhibition of miR-126 in ADSCs failed to increase Akt phosphorylation in histone-exposed HUVECs. CONCLUSION: ADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.


Assuntos
Lesão Pulmonar Aguda , Exossomos , Células-Tronco Mesenquimais , Tecido Adiposo/metabolismo , Animais , Exossomos/metabolismo , Histonas , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
9.
Sci Rep ; 10(1): 16489, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020535

RESUMO

Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3+) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.


Assuntos
Fígado/metabolismo , Mitocôndrias/metabolismo , Sondas Moleculares/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
10.
Life Sci ; 257: 118074, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673667

RESUMO

AIM: Doxorubicin (DOX) induces dose-dependent cardiotoxicity due to reactive oxygen species (ROS)-mediated oxidative stress and subsequent apoptosis of cardiomyocytes. We aimed to assess whether sodium thiosulfate (STS), which has antioxidant and antiapoptotic properties, exerts cardioprotective effects on DOX-induced cardiomyopathy. MAIN METHODS: Male C57BL/6N mice were divided into four groups, control, DOX, STS, and DOX + STS, and administered DOX (20 or 30 mg/kg) or normal saline intraperitoneally, followed by an injection of STS (2 g/kg) or normal saline 4 h later. KEY FINDINGS: The DOX group showed a poorer 6-day survival and decreased cardiac function than the DOX + STS group. The DOX group showed a marked increase in the plasma creatine kinase isoenzyme myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels 10 h after DOX injection, while the DOX + STS group showed suppression of DOX-induced elevation of CK-MB and LDH levels. The DOX group showed increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the heart, whereas the DOX + STS group showed increased catalase and superoxide dismutase (SOD) activities and decreased 8-OHdG levels in the heart compared with DOX group, suggesting that STS reduces DOX-induced DNA damage by improving antioxidant enzymes activities in cardiomyocytes. Additionally, the DOX + STS group showed attenuation of cleaved caspase-3 and DNA fragmentation in cardiomyocytes compared with the DOX group, suggesting that STS suppresses DOX-induced apoptosis in cardiomyocytes. SIGNIFICANCE: STS exerts cardioprotective effects against DOX-induced cardiac dysfunction partly by improving antioxidant defense and suppressing apoptosis, indicating the therapeutic potential of STS against DOX-induced cardiomyopathy.


Assuntos
Cardiotoxicidade/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Tiossulfatos/farmacologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
11.
Int Immunopharmacol ; 83: 106462, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32251961

RESUMO

No effective treatment has been established for autoimmune hepatitis (AIH), except for liver transplantation in the fatal stage. Little is known about the roles and mechanisms of farnesyltransferase inhibitors (FTIs) in treating AIH. Thus, we investigated the specific role of the FTI, tipifarnib, in a Concanavalin A (Con A)-induced model of hepatitis. The effects of tipifarnib (10 mg/kg, intraperitoneal injection) were studied in Con A (20 mg/kg, intravenous injection)-challenged mice by histological, biochemical, and immunological analyses. Tipifarnib-treated mice were compared to phosphate-buffered saline (PBS)-treated mice. Con A caused liver injury characterized by increased plasma alanine aminotransferase (ALT) levels and marked histological changes. The increased serum ALT, interleukin-6, or interferon-γ (IFN-γ) levels were observed at 2 or 8 h; tumor necrosis factor-α levels at 2 h post-Con A administration decreased significantly in the tipifarnib group. Tipifarnib also suppressed Con A-induced activation of CD4+ cells (but not CD8+ T cells) in the liver and spleen, and also reversed the Con A-induced decrease of natural killer T (NKT) cells in the liver. Tipifarnib significantly inhibited IFN-γ production and STAT1 phosphorylation from CD4+ T cells (but not CD8+ T and NKT cells) in the liver at 2 h post-Con A administration. Tipifarnib significantly inhibited IFN-γ production by splenic CD4+ T cells at 48 h post-Con A injection in vitro. Tipifarnib also inhibited the expression of farnesylated proteins induced by Con A administration. In conclusion, tipifarnib inhibited IFN-γ derived from Con A-induced CD4+ T cell activation due to downregulated STAT1 phosphorylation, suggesting that Tipifarnib can protect against AIH.


Assuntos
Antineoplásicos/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Hepatite Autoimune/tratamento farmacológico , Fígado/imunologia , Quinolonas/uso terapêutico , Animais , Células Cultivadas , Concanavalina A/metabolismo , Modelos Animais de Doenças , Hepatite Autoimune/imunologia , Humanos , Interferon gama/metabolismo , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Cyborg Bionic Syst ; 2020: 8378025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-37063410

RESUMO

Early-stage gastrointestinal cancer is often treated by endoscopic submucosal dissection (ESD) using a flexible endoscope. Compared with conventional percutaneous surgery, ESD is much less invasive and provides a high quality of life for the patient because it does not require a skin incision, and the organ is preserved. However, the operator must be highly skilled because ESD requires using a flexible endoscope with energy devices, which have limited degrees of freedom. To facilitate easier manipulation of these flexible devices, we developed a surgical robot comprising a flexible endoscope and two articulating instruments. The robotic system is based on a conventional flexible endoscope, and an extrapolated motor unit moves the endoscope in all its degrees of freedom. The instruments are thin enough to allow insertion of two instruments into the endoscope channel, and each instrument has a bending section that allows for up-down, right-left, and forward-backward motion. In this study, we performed an ex vivo feasibility evaluation using the proposed robotic system for ESD in a porcine stomach. The procedure was successfully performed by five novice operators without complications. Our findings demonstrated the feasibility of the proposed robotic system and, furthermore, suggest that even operators with limited experience can use this system to perform ESD.

13.
Endosc Int Open ; 7(11): E1442-E1447, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31673616

RESUMO

Background and study aims The association of tumor hypoxia and vascularization with malignant progression is recognized, and detection by measuring tissue hemoglobin (Hb) saturation and concentration has attracted attention. In this study, we designed a simple algorithm and multispectral image-processing endoscopy system to map relative Hb concentration and Hb saturation for detection of tumors in small animal viscera in vivo. Materials and methods We designed and validated an optical filter-equipped endoscope system for two-dimensional visualization of Hb concentration and saturation maps and used it in a real-time video examination. A simplified method based on spectral data capture and analysis of defuse reflection of mucosa, including image capture and data processing of the spectral features of Hb oxygenation, was developed. Results An Hb saturation calibration curve was obtained. Then, differences in oxygenation levels between normal mucosa and in vivo tumors in a small animal model were determined by using the new method and endoscope system. Conclusions A multispectral image-processing endoscopic system with a mapping frame rate comparable to that of white light imaging systems (7.5 frames/second) was developed.

14.
Acute Med Surg ; 6(4): 400-403, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31592080

RESUMO

BACKGROUND: Open abdomen management (OAM) is used not only for trauma but also for treatment of peritonitis. However, the rate of successful fascial closure in patients with OAM remains low. CASE PRESENTATION: The patient was a 38-year-old morbidly obese man who underwent laparoscopic sleeve gastrectomy. Twenty days after surgery, postoperative leakage resulted in panperitonitis. In this case, we undertook drainage by open laparotomy. The patient's status was generally unstable and he was treated with OAM. We used flexible silicone mesh as the dressing material for negative-pressure wound therapy. Open abdominal management continued until status improvement (32 days). Fascial closure was eventually successful because of good granulation growth. CONCLUSION: When combined with negative-pressure wound therapy, silicone mesh prevents wound adhesions and infection after surgery. Silicone mesh is useful for patients with increased risk of infection, such as those with diffuse peritonitis.

15.
Int J Clin Oncol ; 24(11): 1333-1349, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522313

RESUMO

INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.


Assuntos
Neoplasias Colorretais/diagnóstico , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/cirurgia , Animais , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/terapia , Quimiocina CXCL12/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Cães , Neoplasias Esofágicas/cirurgia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Humanos , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/terapia , Cuidados Pós-Operatórios , Receptores CXCR4/metabolismo , Procedimentos de Cirurgia Plástica/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
16.
Hepatol Res ; 49(8): 890-901, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30945395

RESUMO

AIM: Idiopathic portal hypertension (IPH), extrahepatic portal obstruction (EHO), and Budd-Chiari syndrome (BCS) are characterized by aberrant portal hemodynamics of unknown etiology. The aim of this study was to explore trends in the descriptive epidemiology of these diseases through periodical nationwide surveys. METHODS: Nationwide epidemiologic surveys were undertaken in 1999, 2005, and 2015 using the same protocol. The survey targets were selected from all departments of gastrointestinal medicine, surgery, pediatrics, and pediatric surgery in Japan by stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of patients with IPH, EHO, and BCS during the preceding year. RESULTS: The estimated number of BCS patients increased from 280 (95% confidence interval, 200-360) in 1999 survey to 410 (300-530) in 2015 survey, whereas the number of IPH and EHO patients has remained largely unchanged during the 15 years (IPH was approximately 1000; EHO was approximately 770 in 2015 survey). The mean age at symptom onset was approximately 45 years for IPH, 30 years for EHO, and 40 years for BCS over the past 15 years. Those who described disease aggravation from the time of diagnosis accounted for approximately 10% of IPH, 15% of EHO, and 20% of BCS patients in each of the three surveys. CONCLUSIONS: In Japan, the prevalence of BCS is increasing, while those of IPH and EHO appear to be stable. Clinical characteristics, including prognoses, have remained largely unchanged in the past 15 years.

17.
Surg Endosc ; 33(2): 651-657, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30187199

RESUMO

BACKGROUND AND AIMS: Colonic endoscopic submucosal dissection (ESD) is time-consuming and bears a high risk of perforation. The aim of the present study was to compare the safety and efficacy between novel articulating devices and conventional ESD in live porcine colon models. METHODS: Thirty ESDs in ten pigs were carried out at three different locations (15, 25, and 35 cm from the anus) by the conventional method (n = 15) and by the new method (n = 15). Procedure times, adverse events (perforation, bleeding), and damage to the muscular layer were recorded, and the ESD time per unit area of the specimens was calculated. RESULTS: The perforation rate using the conventional method was 6.7% (1/15), whereas that using the new method was 0.0%. The number of sites of muscular damage was significantly lower in the new than conventional method (6 vs. 37, respectively; P = 0.024). The mean procedure time was significantly shorter in the new than conventional method (4.6 ± 2.0 vs. 7.0 ± 4.1 min/cm2, respectively; P = 0.042). CONCLUSIONS: Use of the new ESD method allows for reduced adverse events and a shortened resection time.


Assuntos
Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa , Animais , Ressecção Endoscópica de Mucosa/instrumentação , Ressecção Endoscópica de Mucosa/métodos , Modelos Anatômicos , Suínos , Resultado do Tratamento
18.
Comput Math Methods Med ; 2018: 9873273, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29686724

RESUMO

This study investigated whether parameters derived from hand motions of expert and novice surgeons accurately and objectively reflect laparoscopic surgical skill levels using an artificial intelligence system consisting of a three-layer chaos neural network. Sixty-seven surgeons (23 experts and 44 novices) performed a laparoscopic skill assessment task while their hand motions were recorded using a magnetic tracking sensor. Eight parameters evaluated as measures of skill in a previous study were used as inputs to the neural network. Optimization of the neural network was achieved after seven trials with a training dataset of 38 surgeons, with a correct judgment ratio of 0.99. The neural network that prospectively worked with the remaining 29 surgeons had a correct judgment rate of 79% for distinguishing between expert and novice surgeons. In conclusion, our artificial intelligence system distinguished between expert and novice surgeons among surgeons with unknown skill levels.


Assuntos
Inteligência Artificial , Competência Clínica , Laparoscopia , Cirurgiões , Competência Clínica/estatística & dados numéricos , Biologia Computacional , Simulação por Computador , Educação Médica Continuada/estatística & dados numéricos , Estudos de Viabilidade , Mãos , Humanos , Laparoscopia/educação , Aprendizado de Máquina , Movimento , Redes Neurais de Computação , Cirurgiões/educação , Análise e Desempenho de Tarefas
19.
Surg Endosc ; 32(7): 3386-3392, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29667042

RESUMO

BACKGROUND: Difficulties in endoscopic operations and therapeutic procedures seem to occur due to the complexity of operating the endoscope dial as well as difficulty in performing synchronized movements with both hands. We developed a prototype robotic-assisted flexible endoscope that can be controlled with a single hand in order to simplify the operation of the endoscope. The aim of this study was to confirm the operability of the robotic-assisted flexible endoscope (RAFE) by performing endoscopic submucosal dissection (ESD). METHODS: Study 1: ESD was performed manually or with RAFE by an expert endoscopist in ex vivo porcine stomachs; six operations manually and six were performed with RAFE. The procedure time per unit circumferential length/area was calculated, and the results were statistically analyzed. Study 2: We evaluated how smoothly a non-endoscopist can move a RAFE compared to a manual endoscope by assessing the designated movement of the endoscope. RESULTS: Study 1: En bloc resection was achieved by ESD using the RAFE. The procedure time was gradually shortened with increasing experience, and the procedure time of ESD performed with the RAFE was not significantly different from that of ESD performed with a manual endoscope. Study 2: The time for the designated movement of the endoscope was significantly shorter with a RAFE than that with a manual endoscope as for a non-endoscopist. CONCLUSIONS: The RAFE that we developed enabled an expert endoscopist to perform the ESD procedure without any problems and allowed a non-endoscopist to control the endoscope more easily and quickly than a manual endoscope. The RAFE is expected to undergo further development.


Assuntos
Endoscópios , Ressecção Endoscópica de Mucosa/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/cirurgia , Animais , Ressecção Endoscópica de Mucosa/métodos , Suínos
20.
Int J Comput Assist Radiol Surg ; 13(7): 1063-1072, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29492881

RESUMO

PURPOSE: Image guidance is a key technology that can improve the outcome of laparoscopic surgery. However, due to the large deformation caused by digestive organs, a computer-aided navigation system based on preoperative imaging data cannot indicate the correct target position of the lesion (e.g., liver tumors and vessels invisible from the organ surface). To overcome this issue, we developed a laparoscopic ultrasound manipulator with two motorized degrees of freedom at the tip, allowing for the performance of a dexterous ultrasound scan in a confined laparoscopic surgical area. METHOD: The developed manipulator consists of a compact and elastic structure using springs, enabling a safe ultrasound scan and avoiding excess force on the inspected organs. The manipulator is a handheld device equipped with four buttons at the handle, which the surgeon directly grasps to send a motion command to the tip structure. The developed prototype realizes two motorized degree-of-freedom motion at the tip. The size of prototype is 15.0 mm in diameter that is usable in conventional laparoscopy. The tip of the manipulator was carefully designed by considering the kinematic model and the results of the finite element analysis. RESULTS: To assess the prototype, accuracy and rigidity were measured by using a motion processing microscope. The accuracy test showed that the proposed device has a fairly accurate characteristic as a handheld device. This was supposedly caused by the nature of compliant mechanism, which does not have mechanical play in motion. In addition, the intrinsic elastic structure (approximately 2.0 N/mm in most of the range of motion) allowed the ultrasound probe to adequately fit on the curved organ surface without extra effort of manipulation during the inspection. In the in vivo experiment, the yaw motion was found to be effective for investigating the vascular network because the manipulator allows the probe to be rotated while maintaining the same position. CONCLUSION: The mechanical evaluation and in vivo test results showed high feasibility of the prototype. We are currently working on further mechanical improvement for commercialization and development of a real-time navigation system that can perform three-dimensional reconstruction of ultrasonographic images by implementing a magnetic position sensor at the tip of the manipulator.


Assuntos
Desenho de Equipamento , Laparoscopia/instrumentação , Cirurgia Assistida por Computador/instrumentação , Ultrassonografia de Intervenção/instrumentação , Fenômenos Biomecânicos , Humanos , Laparoscopia/métodos , Movimento (Física) , Cirurgia Assistida por Computador/métodos , Instrumentos Cirúrgicos , Ultrassonografia de Intervenção/métodos
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