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More efficient induction of genotoxicity by high-LET Fe-particle radiation than low-LET X-ray radiation at low doses

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Radiation Medicine and Protection 2023年第1期4卷 11-18页

作者： Bing Wang Takanori Katsube Kaoru Tanaka Yasuharu Ninomiya Hirokazu Hirakawa Cuihua Liu Kouichi Maruyama Masahiro Murakami Tetsuo Nakajima Akira Fujimori Mitsuru Nenoi National Institutes for Quantum Science and Technology Chiba263-8555Japan

Objective:To understand differential effects on induction of genotoxicity and genomic instability(GI)by high-LET particle radiation and low-LET photon radiation,based on ground-based experiments using total body irradiation(TBI)of mice with Fe-particle radiation and X-ray radiation.Methods:TBI was delivered to C57BL/6J Jms strain female mice of 8 weeks old at a dose ranging from 0.1 to 3.0 Gy of Fe-particle radiation or at a dose ranging from 0.1 to 5.0 Gy of X-ray radiation.Induction of genotoxicity and GI by TBI was determined respectively at 1 and 2 months after exposure using frequency of micronuclei in bone marrow erythrocytes as the endpoint.Inhibition of bone marrow cell proliferation by TBI was measured as reduced erythropoiesis.Physiological conditions were also investigated.Results:TBI,regardless of the type of radiation,caused statistically significant increase in genotoxicity at 1 month after exposure,but did not induce GI at 2 months after exposure even at higher doses(>1.0 Gy).The doseresponse curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7798 t 1.7889x–0.5978x^(2)(R^(2)=0.8109)and y=0.7421 t 1.3792x–0.2588 x^(2)(R^(2)=0.8081),respectively.The dose-response curve for the frequency of micronucleated normochromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7191 t 1.4545x–0.4978x^(2)(R^(2)=0.7047)and y=0.658 t 1.344x–0.2531x^(2)(R^(2)=0.7853),respectively.In general,high-LET Fe-particle radiation was more efficient in inducing genotoxicity than low-LET X-ray radiation at lower doses(<0.5 Gy).Conclusions:These results further confirm that exposure to TBI,even at higher doses and regardless the type of radiation,does not induce GI in C57BL/6J strain mice measured as increased micronuclei in bone marrow erythrocytes.These findings indicate that radiation-induced GI is mouse strain dependent and suggest that more comprehensive studies should be done to explore the late health consequences fro

关键词： Fe-particle radiation Genotoxicity Genomic instability Micronucleated erythrocyte C57BL/6J mice

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Non-alcoholic fatty liver disease later diagnosed as myotonic dystrophy

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World Journal of Hepatology 2020年第9期12卷 685-692页

作者： Naoki Tanaka Takefumi Kimura Naoyuki fujimori Yasuyuki Ichise Kenji Sano akira Horiuchi Department of Metabolic Regulation Shinshu University School of MedicineMatsumoto 390-8621Japan Department of Gastroenterology Shinshu University School of MedicineMatsumoto 390-8621Japan Digestive Disease Center Showa Inan General HospitalKomagane 399-4117Japan Department of Pathology Iida Municipal HospitalIida 395-8502Japan

BACKGROUND Myotonic dystrophy(MD)is sometimes accompanied by metabolic/endocrine disorders,including dyslipidemia,central obesity,and hypogonadism.Due to considerable individual differences in the severity and progression of myopathy,MD patients with minimal-to-mild muscle symptoms might be followed as having other diseases,such as non-alcoholic fatty liver disease(NAFLD).CASE SUMMARY A 40-year-old non-obese man without a history of regular ethanol consumption was referred to our hospital due to persistent liver dysfunction and hyperlipidemia.His body mass index was 23.4 kg/m2.Liver histology demonstrated macrovesicular steatosis,ballooned hepatocytes with eosinophilic inclusion bodies,and perisinusoidal fibrosis,leading to the diagnosis of nonalcoholic steatohepatitis(NASH).Although he had no discernable muscle pain or weakness,persistently high serum creatine kinase(CK)and myoglobin levels as well as the presence of frontal baldness,a hatched face,history of cataract surgery,and grip myotonia indicated the possibility of MD.Southern blotting of the patient’s DNA revealed the presence of CTG repeats,confirming the diagnosis.CONCLUSION When gastroenterologists encounter NAFLD/NASH patients,serum CK should be verified.If hyperCKemia,frontal baldness,a hatched face,history of cataract surgery,and grip myotonia are noted,the possibility of MD may be considered.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Frontal baldness Cataract Creatine kinase

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Prospective real-time evaluation of diagnostic performance using endocytoscopy in differentiating neoplasia from nonneoplasia for colorectal diminutive polyps(≤ 5 mm)

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World Journal of Gastrointestinal Oncology 2018年第4期10卷 96-102页

作者： Takahiro Utsumi Yasushi Sano Mineo Iwatate Hironori Sunakawa akira Teramoto Daizen Hirata Santa Hattori Wataru Sano Noriaki Hasuike Kazuhito Ichikawa Takahiro fujimori Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC) Sano Hospital Department of Pathology Shinko Hospital

AIM To clarify the diagnostic performance of endocytoscopy for differentiation between neoplastic and nonneoplastic colorectal diminutive polyps.METHODS Patients who underwent endocytoscopy between October and December 2016 at Sano Hospital were prospectively recruited. When diminutive polyps(≤5 mm) were detected, the lesions were evaluated by endocytoscopy after being stained with 0.05% crystal violet and 1% methylene blue. The diminutivepolyps were classified into five categories(EC 1 a, 1 b, 2, 3 a, and 3 b). Endoscopists were asked to take a biopsy from any lesion diagnosed as EC1 b(indicator of hyperplastic polyp) or EC2(indicator of adenoma). We have assessed the diagnostic performance of endocytoscopy for EC2 and EC1 b lesions by comparison with the histopathology of the biopsy specimen. RESULTS A total of 39 patients with 63 diminutive polyps were analyzed. All polyps were evaluated by endocytoscopy. The mean polyp size was 3.3 ± 0.9 mm. Among the 63 diminutive polyps, 60 were flat and 3 were pedunculated. The mean time required for EC observation, including the time for staining with crystal violet and methylene blue, was 3.0 ± 1.9 min. Histopathologic evaluation showed that 13 polyps were hyperplastic and 50 were adenomas. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of EC2 for adenoma compared with EC1 b for hyperplastic polyp were 98.0%, 92.3%, 96.8%, 98.0% and 92.3%, respectively. There were only two cases of disagreement between the endoscopic diagnosis made by endocytoscopy and the corresponding histopathological diagnosis.CONCLUSION Endocytoscopy showed a high diagnostic performance for differentiating between neoplastic and non-neoplastic colorectal diminutive polyps, and therefore has the potential to be used for "real-time histopathology".

关键词： Endocytoscopy Diagnostic performance Diminutive polyp Endocytoscopic classification Realtime histopathology

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Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment

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World Journal of Gastroenterology 2023年第40期29卷 5566-5581页

作者： Aitoshi Hoshimoto Atsushi Tatsuguchi Ryohei Hamakubo Takayoshi Nishimoto Jun Omori Naohiko Akimoto Shu Tanaka Shunji fujimori Tsutomu Hatori akira Shimizu Katsuhiko Iwakiri Department of Gastroenterology Nippon Medical SchoolTokyo 113-8603Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo 113-8603Japan Department of Pathology Nippon Medical SchoolChiba Hokusoh HospitalChiba 270-1694Japan

BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and

关键词： Small bowel adenocarcinoma Programmed cell death-ligand 1 Programmed cell death-ligand 2 Tumor microenvironment Tumor-infiltrating lymphocytes Regulatory T-cells

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Endoscopic approach through the minor papilla for the management of pancreatic diseases

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World Journal of Gastrointestinal Endoscopy 2013年第3期5卷 81-88页

作者： Nao fujimori Hisato Igarashi akira Asou Ken Kawabe Lingaku Lee Takamasa Oono Taichi Nakamura Yusuke Niina Masayuki Hijioka Masahiko Uchida Kazuhiro Kotoh Kazuhiko Nakamura Tetsuhide Ito Ryoichi Takayanagi Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityHigashi-kuFukuoka 812-8582Japan Department of Gastroenterology National Hospital OrganizationKyushu Medical CenterChuou-kuFukuoka 810-8563Japan

AIM:To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases.METHODS:This study included 44 endoscopic retrograde cholangiopancreatography(ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012.We retrospectively evaluated the clinical profiles of the patients,the endoscopic interventions,short-term outcomes,and complications.RESULTS:Of 44 ERCPs,26 were diagnostic ERCP,and 18 were therapeutic ERCP.The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung's duct.The overall success rate of minor papilla cannulation was 80%(35/44),which was significantly improved by wire-guided cannulation(P = 0.04).Endoscopic minor papillotomy(EMP) was performed in 17 of 34 patients(50%) using a needle-knife(13/17) or a pull-type papillotome(4/17).EMP with pancreatic stent placement,which was the main therapeutic option for patients with chronic pancreatitis,recurrent acute pancreatitis,and pancreatic pseudocyst,resulted in short-term clinical improvement in 83% of patients.Mild post-ERCP pancreatitis occurred as an early complication in 2 cases(4.5%).CONCLUSION:The endoscopic minor papilla approach is technically feasible,safe,and effective when the procedure is performed in a high-volume referral center by experienced endoscopists.

关键词： Endoscopic papillotomy Endoscopic retrograde cholangiopancreatography Minor papilla Pancreas divisum Pancreatitis

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