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Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 581-589页

作者： Yuichi Hori Tsukasa Ikeura Takashi Yamaguchi Katsunori Yoshida Koichi Matsuzaki mitsuaki ishida Sohei Satoi Kazuichi Okazaki Department of Gastroenterology and Hepatology Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan Department of Pathology Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan Department of Surgery Kansai Medical University2-5-1 ShinmachiHirakataOsaka 5731191Japan

Background:Malignant intraductal papillary mucinous neoplasm(IPMN)has poor prognosis.The carcinogenesis of IPMN is not clear.The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods:By using immunohistochemistry,we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013.We also examined the expression of Ki-67,c-Myc and p-JNK.Results:The median immunostaining index of pSmad3C was 79.2%in low-grade dysplasia,74.9%in highgrade dysplasia,and 42.0%in invasive carcinoma(P<0.01),whereas that of pSmad3L was 3.4%,4.3%,and 42.4%,respectively(P<0.01).There was a negative relationship between the expression of pSmad3C and c-Myc(P<0.001,r=-0.615)and a positive relationship between the expression of pSmad3L and c-Myc(P<0.001,r=0.696).Negative relationship between the expression of pSmad3C and Ki-67(P<0.01,r=-0.610)and positive relationship between the expression of pSmad3L and Ki-67(P<0.01,r=0.731)were confirmed.p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells.The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58(range,0.05–0.93),3.83(range,0.85–5.96),respectively(P=0.02).The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91(range,0–36.9)and 82.1(range,46.2–97.1),respectively(P=0.02).The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9(range 5.7–30.8)and 90.9(range 52.9–98.5),respectively(P=0.02).Conclusions:pSmad3L was upregulated in malignant IPMN.pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

关键词： Intraductal papillary mucinous neoplasms of the pancreas Immunohistochemistry Phosphorylated Smad Carcinogenesis Prognosis

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Hepatocellular carcinoma occurring in a Crohn’s disease patient

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World Journal of Gastroenterology 2010年第25期16卷 3215-3218页

作者： mitsuaki ishida Shigeyuki Naka Hisanori Shiomi Tomoyuki Tsujikawa Akira Andoh Tamio Nakahara Yasuharu Saito Yoshi-hide Fujiyama Mikiko Takikita-Suzuki Fumiyoshi Kojima Machiko Hotta Tohru Tani Yoshimasa Kurumi Hidetoshi Okabe Department of Clinical Lab-oratory Medicine and Division of Diagnostic Pathology Shiga University of Medical Science Otsu Shiga 520-2192 Japan Department of Surgery Shiga University of Medical Sci-ence Otsu Shiga 520-2192 Japan Department of Gastroenterology Shiga Uni-versity of Medical Science Otsu Shiga 520-2192 Japan Division of Endoscopy Shiga University of Medical Science Otsu Shiga 520-2192 Japan

We report a case of hepatocellular carcinoma (HCC) occurring in a patient with Crohn’s disease (CD) without chronic hepatitis or liver cirrhosis, and review the clinicopathological features of HCC in CD patients. A 37-year-old Japanese man with an 8-year history of CD and a medication history of azathioprine underwent resection of a liver tumor. The histopathology of the liver tumor was pseudoglandular type HCC. In the nonneoplastic liver, focal hepatocyte glycogenosis (FHG) was observed, however, there was no evidence of liver cirrhosis or primary sclerosing cholangitis. Only nine cases of HCC in CD patients have been reported previously in the English-language literature. Eight of 10cases (including the present case) had received azathioprine treatment, and four of these cases also showed FHG, which is considered a preneoplastic liver lesion, within the non-neoplastic liver. Although the precise mechanism of the development of HCC in CD patients is controversial, these results suggest that azathioprine therapy and FHG in the non-neoplastic liver contribute to the development of HCC. These findings also indicate that it is important to survey CD patients treated with prolonged azathioprine therapy for potential liver tumors.

关键词： Crohn’s disease Hepatocellular carcinoma Azathioprine Focal hepatocyte glycogenosis Hepato-carcinogenesis

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Primary cutaneous anaplastic large cell lymphoma with subsequent leg involvement

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World Journal of Dermatology 2012年第3期1卷 38-40页

作者： mitsuaki ishida Norikazu Fujii Hidetoshi Okabe Division of Diagnostic Pathology Department of Clinical Laboratory Medicine Shiga University of Medical Science Shiga 520-2192 Japan Department of Dermatology Shiga University of Medical Science Shiga 520-2192 Japan

Primary cutaneous anaplastic large cell lymphoma(CALCL)is regarded as an indolent type of cutaneous T-cell lymphoma.However,a few recent publications revealed that C-ALCL patients with initial leg involvement had significantly worse survival than those without initial leg involvement.Herein,we report a case of C-ALCL with subsequent leg involvement,which led to death after chemoradiation therapy.A 75 years old Japanese man presented with multiple erythematous nodules in his left arm and the side of his left chest.Histopathological and immunohistochemical studies led to the diagnosis of primary C-ALCL.At the initial diagnosis,no leg lesion was found.One year after the initial diagnosis,C-ALCL appeared in his right lower thigh and left hip.Radiation therapy,low-dose etoposide and CHOP therapy were performed;however,the patient died of malignant lymphoma 4 years after the initial diagnosis.We speculated that the occurrence of subsequent leg involvement may also be indicative of a worse prognosis,as in the case with initial leg involvement in C-ALCL.Therefore,we propose that C-ALCL patients with initial or subsequentleg involvement should be classified as a distinct clinicopathological variant of C-ALCL("leg-type"involvement)and that they may require intense therapy.

关键词： Cutaneous lymphoma Cutaneous CD30-positive T-cell lymphoproliferative lesion Primary cutaneous anaplastic large cell lymphoma Leg involvement Prognosis Chemotherapy

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Pigmented hidroacanthoma simplex:A diagnostic pitfall

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World Journal of Dermatology 2012年第2期1卷 10-12页

作者： mitsuaki ishida Fumiyoshi Kojima Machiko Hotta Yasuhiro Iwai Hidetoshi Okabe Division of Diagnostic Pathology and Department of Clinical Laboratory Medicine Shiga University of Medical Science Division of Diagnostic Pathology Takatsuki Hospital

Hidroacanthoma simplex(HAS) is a rare skin appendage tumor and is recognized as an intraepidermal variant of poroma. Pigmented HAS is an extremely rare variant with dendritic melanocytes and/or melanin pigment in the tumor cells and a few cases of pigmented HAS have been reported in the English literature. We herein report a case of pigmented HAS and discuss the clinicopathological features of pigmented HAS and the pitfall in the diagnosis of black lesions.

关键词： Pigmented hidroacanthoma simplex Seborrheic keratosis Porocarcinoma Skin appendage tumor Clinicopathological features

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A rare case of primary choriocarcinoma in the sigmoid colon

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World Journal of Gastroenterology 2013年第39期19卷 6683-6688页

作者： Hiromitsu Maehira Tomoharu Shimizu Hiromichi Sonoda Eiji Mekata Tomoharo Yamaguchi Tohru Miyake mitsuaki ishida Tohru Tani Department of Surgery Shiga University of Medical ScienceShiga 520-2192Japan Department of Clinical Laboratory Medicine Shiga University of Medical ScienceShiga 520-2192Japan

Primary colorectal choriocarcinoma is an extremely rare neoplasm and is usually associated with a poor prognosis.Only 13 cases of colorectal choriocarcinoma have previously been reported.There is no standard chemotherapeutic regimen for this tumor type.A 68-year-old man presented with melena and was diagnosed with sigmoid colonic adenocarcinoma with multiple liver metastases.He underwent a laparoscopic sigmoidectomy.Pathology revealed choriocarcinoma with a focal component of moderately differentiated adenocarcinoma of colon origin.Based on the collagen gel droplet-embedded culture drug sensitivity test(CD-DST)results,mFOLFOX6 and bevacizumab were administered,which suppressed aggressive tumor growth for 4 mo.The patient died 9 mo after the initial diagnosis.Our study results suggest that the standard chemotherapy regimen for colorectal cancer might have suppressive effects against primary colorectal choriocarcinoma.Moreover,CD-DST may provide,at least in part,therapeutic insight for the selection of appropriate antitumor agents for such patients.

关键词： Colon cancer Colorectal cancer Chemotherapy Culture drug sensitivity test Choriocarcinoma

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Hepatic reactive lymphoid hyperplasia in a patient with primary biliary cirrhosis

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World Journal of Hepatology 2010年第10期2卷 387-391页

作者： mitsuaki ishida Tamio Nakahara Yousuke Mochizuki Tomoyuki Tsujikawa Akira Andoh Yasuharu Saito Hiroshi Yamamoto Fumiyoshi Kojima Machiko Hotta Tohru Tani Yoshihide Fujiyama Hidetoshi Okabe Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology Shiga University of Medical Sci enceOtsuShiga 520-2192Japan Department of Gastroenterology Shiga University of Medical ScienceOtsuShiga 520-2192Japan Division of Endoscopy Shiga University of Medical ScienceOtsuShiga 520-2192Japan Department of Surgery Shiga University of Medical ScienceOtsuShiga 520-2192Japan

Reactive lymphoid hyperplasia(RLH) of the liver is an extremely rare lesion characterized by the proliferation of non-neoplastic lymphocytes forming follicles.Hepatic RLH is known to be associated with gastrointestinal carc inoma and autoimmune diseases including primary biliary cirrhosis(PBC).We report a case of hepatic RLH in a patient with PBC and gastric cancer.A 68 year old Japanese woman with a 10 year history of liver enzyme abnormality was admitted.Laboratory testing revealed that her anti-mitochondrial antibody was markedly elev ated.Five mo after the diagnosis of PBC,she was foun d to have gastric cancer.Abdominal computed tom og raphy disclosed a liver nodule in S8,suggesting metas tatic gastric carcinoma.Histopathologically,the resected liver lesion comprised of a nodular proliferation of small lym phocytes with lymphoid follicles.This is the first reported case of hepatic RLH in a patient with both PBC and gastric cancer.Pre-operative diagnosis of hepatic RLH by clinical imaging is extremely difficult.Therefore,a need le biopsy could be useful to make a diagnosis of hepat ic RLH,especially to differentiate from metastatic gastroin t estinal carcinoma.

关键词： Reactive lymphoid hyperplasia Pseudolymphoma Liver Primary biliary cirrhosis Gastric cancer

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Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct

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World Journal of Gastrointestinal Oncology 2011年第7期3卷 111-115页

作者： mitsuaki ishida Tsuyoshi Mori Hisanori Shiomi Shigeyuki Naka Tomoyuki Tsujikawa Akira Andoh Yasuharu Saito Yoshimasa Kurumi Fumiyoshi Kojima Machiko Hotta Tohru Tani Yoshihide Fujiyama Hidetoshi Okabe Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology Shiga University of Medical Science Department of Surgery Shiga University of Medical Science Department of Gastroenterology Shiga University of Medical Science Division of Endoscopy Shiga University of Medical Science

A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma(LEC),and some of LEC is associated with Epstein-Barr virus(EBV).All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location.Herein,we describe the first case of LEC of the inferior common bile duct.A 68-year-old Japanese man,who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy,was found to have tumors of the common bile duct and pancreas head.Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli.Around the tumor cell nests,dense lymphoplasmacytic infiltration was observed.Focal glandular differentiation(approximately 5%) was also present.These histopathological features corresponded morphologically to LEC.Immunohistochemically,the tumor cells were positive for cytokeratin(CK) 7,CK 19 and CA19-9,but negative for CK 20 and Hep Par 1.In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells.Therefore,a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made.Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma,the differences in prognosis between EBV-positive and-negative cases have not yet been established.Therefore,additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.

关键词： Lymphoepithelioma-like carcinoma EpsteinBarr virus Common bile duct

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Gravitational wave footprints from Higgs-portal scalegenesis with multiple dark chiral scalars

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Chinese Physics C 2024年第4期48卷 209-221页

作者： He-Xu Zhang Shinya Matsuzaki Hiroyuki ishida Center for Theoretical Physics and College of Physics Jilin UniversityChangchun 130012China Center for Liberal Arts and Sciences Toyama Prefectural UniversityToyama 939-0398Japan

We discuss the gravitational wave(GW)spectra predicted from the electroweak scalegenesis of the Higgs portal type with a large number of dark chiral flavors,which many flavor QCD would underlie and give the dynamical explanation of the negative Higgs portal coupling required to trigger the electroweak symmetry breaking.We employ the linear-sigma model as the low-energy description of dark many flavor QCD and show that the model undergoes ultra-supercooling due to the produced strong first-order thermal phase transition along the(approximately realized)flat direction based on the Gildener-Weinberg mechanism.Passing through evaluation of the bubble nucleation/percolation,we address the reheating and relaxation processes,which are generically non-thermal and nonadiabatic.Parametrizing the reheating epoch in terms of the e-folding number,we propose proper formulae for the redshift effects on the GW frequencies and signal spectra.It then turns out that the ultra-supercooling predicted from the Higgs-portal scalegenesis generically yields none of GW signals with the frequencies as low as nano Hz,unless the released latent heat is transported into another sector other than reheating the universe.Instead,models of this class prefer to give the higher frequency signals and still keeps the future prospected detection sensitivity,like at LISA,BBO,and DECIGO,etc.We also find that with large flavors in the dark sector,the GW signals are made further smaller and the peak frequencies higher.Characteristic phenomenological consequences related to the multiple chiral scalars include the prediction of dark pions with the mass much less than TeV scale,which is also briefly addressed.

关键词： gravitational wave electroweak scalegenesis many flavor QCD

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Z-shaped incision without epithelial resection in pterygium surgery

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1262-1266页

作者： Satoru Kase Shinki Chin Susumu ishida Department of Ophthalmology Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporo 060-8638Japan

AIM:To introduce a novel surgical technique using a Z-shaped incision without epithelial resection in ophthalmic pterygia.METHODS:This was a prospective study.During pterygium surgery,all proliferative tissues were separated from the cornea and conjunctiva without resection of the tissues.The unaffected conjunctiva was incised in a Z-shape.The upper(or lower)conjunctival flap was sutured to the lower(or upper)normal conjunctiva on the limbal sclera,while the proliferative tissue was sutured to the upper conjunctiva(or lower)near the fornix.RESULTS:Ten patients with pterygia were eligible for this study.Eight patients with primary pterygia and 2 with recurrent pterygia were included.The age of patients at surgery ranged from 47 to 90y(average:71.9y).Five patients each showed right and left-sided pterygia.The postoperative follow-up periods were from 8 to 78mo(average:25.0mo).The surgery was successfully conducted and wounds were favorably reconstructed in all patients.The proliferative tissues sutured to the normal conjunctiva showed palor and attenuated neovessles,and never showed re-growth after surgery.Nine patients did not show recerrence.Recerrent pterygium was noted in 1 patient,but additional treatments were not required.CONCLUSION:The procedure involves the reconstruction of pterygial tissue and normal conjunctiva using a Z-shaped incision.The scleral limbal wound can be covered with nonaffected conjunctiva without any excision of conjunctival epithelia in patients with primary or recurrent pterygia.

关键词： pterygium surgery Z-shape non-resection

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Gravitational wave footprints from Higgs-portal scalegenesis with multiple dark chiral scalars

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Chinese Physics C 2024年第4期 213-225页

作者：张贺旭 Shinya Matsuzaki Hiroyuki ishida Center for Theoretical Physics and College of Physics Jilin University Center for Liberal Arts and Sciences Toyama Prefectural University

We discuss the gravitational wave(GW) spectra predicted from the electroweak scalegenesis of the Higgs portal type with a large number of dark chiral flavors, which many flavor QCD would underlie and give the dynamical explanation of the negative Higgs portal coupling required to trigger the electroweak symmetry breaking.We employ the linear-sigma model as the low-energy description of dark many flavor QCD and show that the model undergoes ultra-supercooling due to the produced strong first-order thermal phase transition along the(approximately realized) flat direction based on the Gildener-Weinberg mechanism. Passing through evaluation of the bubble nucleation/percolation, we address the reheating and relaxation processes, which are generically non-thermal and nonadiabatic. Parametrizing the reheating epoch in terms of the e-folding number, we propose proper formulae for the redshift effects on the GW frequencies and signal spectra. It then turns out that the ultra-supercooling predicted from the Higgs-portal scalegenesis generically yields none of GW signals with the frequencies as low as nano Hz,unless the released latent heat is transported into another sector other than reheating the universe. Instead, models of this class prefer to give the higher frequency signals and still keeps the future prospected detection sensitivity, like at LISA, BBO, and DECIGO, etc. We also find that with large flavors in the dark sector, the GW signals are made further smaller and the peak frequencies higher. Characteristic phenomenological consequences related to the multiple chiral scalars include the prediction of dark pions with the mass much less than Te V scale, which is also briefly addressed.

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