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  1. Article ; Online: Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study.

    Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

    Virchows Archiv : an international journal of pathology

    2024  

    Abstract: Genetic alterations including fusions in fibroblast growth factor receptor 2 (FGFR2) are detected in 10-20% of intrahepatic cholangiocarcinoma (iCCA), and FGFR2 inhibitors are effective for the treatment of iCCA. We examined a prevalence of FGFR2 genetic ...

    Abstract Genetic alterations including fusions in fibroblast growth factor receptor 2 (FGFR2) are detected in 10-20% of intrahepatic cholangiocarcinoma (iCCA), and FGFR2 inhibitors are effective for the treatment of iCCA. We examined a prevalence of FGFR2 genetic alterations and their clinicopathological significance in combined hepatocellular-cholangiocarcinoma (cHCC-CCA). FGFR2 expression, which is a surrogate marker for FGFR2 genetic alterations, was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 35 with small duct-type iCCA, 30 with large duct-type iCCA, and 35 with hepatocellular carcinoma (HCC). FGFR2 genetic alterations were detected by reverse transcription-PCR and direct sequence. An association of FGFR2 expression with clinicopathological features was investigated in cHCC-CCAs. FGFR2 expression was detected in significantly more patients with cHCC-CCA (21.3%) and small duct-type iCCA (25.7%), compared to those with large duct-type iCCA (3.3%) and HCC (0%) (p < 0.05). FGFR2-positive cHCC-CCAs were significantly smaller size (p < 0.05), with more predominant cholangiolocarcinoma component (p < 0.01) and less nestin expression (p < 0.05). Genetic alterations of ARID1A and BAP1 and multiple genes were significantly more frequent in FGFR2-positive cHCC-CCAs (p < 0.05). 5'/3' imbalance in FGFR2 genes indicating exon18-truncated FGFR2 was significantly more frequently detected in FGFR2-positive cHCC-CCAs and small duct iCCAs, compared to FGFR2-negative ones (p < 0.05). FGFR2::BICC fusion was detected in a case of cHCC-CCAs. FGFR2 genetic alterations may be prevalent in cHCC-CCAs as well as small duct-type iCCAs, which suggest cHCC-CCAs may also be a possible therapeutic target of FGFR2 inhibitors.
    Language English
    Publishing date 2024-03-27
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-024-03792-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud III Zs.10: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Pathologic significance of peribiliary capillary plexus in gallbladder neoplasm.

    Nakanuma, Yasuni / Kakuda, Yuko / Sato, Yasunori / Fukushima, Mana / Sugino, Takashi

    Human pathology

    2024  Volume 146, Page(s) 86–94

    Abstract: Aims: Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), ...

    Abstract Aims: Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP.
    Materials and methods: High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls.
    Results: In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion).
    Conclusion: A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.
    Language English
    Publishing date 2024-04-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207657-3
    ISSN 1532-8392 ; 0046-8177
    ISSN (online) 1532-8392
    ISSN 0046-8177
    DOI 10.1016/j.humpath.2024.04.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Bile duct adenoma and small-sized small duct type intrahepatic cholangiocarcinoma show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components.

    Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

    Histopathology

    2023  Volume 83, Issue 2, Page(s) 298–309

    Abstract: Aims: Given that bile duct adenoma was significantly more prevalent in the liver with small duct type intrahepatic cholangiocarcinoma (small duct iCCA), compared to other primary liver carcinomas, we examined the possibility of bile duct adenoma as a ... ...

    Abstract Aims: Given that bile duct adenoma was significantly more prevalent in the liver with small duct type intrahepatic cholangiocarcinoma (small duct iCCA), compared to other primary liver carcinomas, we examined the possibility of bile duct adenoma as a precursor of small duct iCCA by analysing genetic alterations and other features in bile duct adenomas.
    Methods and results: Subjects included 33 bile duct adenomas and 17 small-sized (up to 2 cm in diameter) small duct iCCAs. Genetic alterations were examined by direct sequencing for hot-spot regions and immunohistochemical staining. The expression of p16
    Conclusion: Bile duct adenomas and small-sized small duct iCCAs show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components. There was no evidence suggesting that bile duct adenoma is a precursor of small duct iCCA. Immunohistochemical staining for IMP3, EZH2, p53, ARID1A and MTAP may be useful for differential diagnosis between bile duct adenomas and small duct iCCAs.
    MeSH term(s) Humans ; Adenoma, Bile Duct/pathology ; Bile Duct Neoplasms/metabolism ; Bile Ducts, Intrahepatic/pathology ; Cholangiocarcinoma/pathology ; Tumor Suppressor Protein p53
    Chemical Substances Tumor Suppressor Protein p53 ; EZH2 protein, human (EC 2.1.1.43) ; IGF2BP3 protein, human
    Language English
    Publishing date 2023-05-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.14932
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1328: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: An involvement of Hippo-yes-associated protein pathway in biliary epithelial senescence in primary biliary cholangitis.

    Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

    Clinics and research in hepatology and gastroenterology

    2023  Volume 47, Issue 4, Page(s) 102106

    Abstract: Background & aims: Accumulating evidence suggest that Hippo-yes-associated protein (YAP) pathway plays important roles in development and repair after injuries in biliary system. We disclosed that senescent biliary epithelial cells (BECs) participate in ...

    Abstract Background & aims: Accumulating evidence suggest that Hippo-yes-associated protein (YAP) pathway plays important roles in development and repair after injuries in biliary system. We disclosed that senescent biliary epithelial cells (BECs) participate in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that dysregulation of Hippo-YAP pathway may be associated with biliary epithelial senescence in pathogenesis of PBC.
    Approach & results: Cellular senescence was induced in cultured BECs by treatment with serum depletion or glycochenodeoxycholic acid. The expression and activity of YAP1 were significantly decreased in senescent BECs (p<0.01). Cellular senescence and apoptosis were significantly increased (p<0.01) and a proliferation activity and a 3D-cyst formation activity were significantly decreased (p<0.01) by a knockdown of YAP1 in BECs. The expression of YAP1 were immunohistochemically determined in livers taken from the patients with PBC (n = 79) and 79 control diseased and normal livers and its association with senescent markers p16
    Conclusion: Dysregulation of Hippo-YAP1 pathway may be involved in the pathogenesis of PBC in association with biliary epithelial senescence.
    MeSH term(s) Humans ; Liver Cirrhosis, Biliary ; YAP-Signaling Proteins ; Cyclin-Dependent Kinase Inhibitor p16 ; Bile Ducts/pathology ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Epithelial Cells/metabolism
    Chemical Substances YAP-Signaling Proteins ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p21
    Language English
    Publishing date 2023-02-26
    Publishing country France
    Document type Journal Article
    ZDB-ID 2594333-9
    ISSN 2210-741X ; 2210-7401
    ISSN (online) 2210-741X
    ISSN 2210-7401
    DOI 10.1016/j.clinre.2023.102106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Nestin may be a candidate marker for differential diagnosis between small duct type and large duct type intrahepatic cholangiocarcinomas.

    Sasaki, Motoko / Sato, Yasunori / Nakanuma, Yasuni

    Pathology, research and practice

    2023  Volume 253, Page(s) 155061

    Abstract: Backgrounds/aims: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small and large duct types. These two subtypes show distinct differences in various clinicopathological features and possible cell origin and pathways of carcinogenesis, ... ...

    Abstract Backgrounds/aims: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small and large duct types. These two subtypes show distinct differences in various clinicopathological features and possible cell origin and pathways of carcinogenesis, however, a differential diagnosis may be sometimes difficult. Given the type IV intermediate filament, Nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and small duct type iCCAs, the significance of nestin as a differential diagnostic marker between small and large duct types of iCCAs was addressed in the present study.
    Methods: Nestin expression was immunohistochemically assessed in the sections from 36 patients with small duct-type iCCA, 30 with large duct-type iCCA, and 27 with extrahepatic cholangiocarcinoma (CCA). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in small duct type iCCAs.
    Results: Nestin expression was detected in 17 small duct type iCCAs (47.2%), one large duct type iCCA (3.8%) and zero extrahepatic CCA. Nestin expression was significantly more frequent in the patients with small duct type iCCAs than in those with large duct type iCCA and extrahepatic CCA (p < 0.01). In 10 liver biopsies, all samples with nestin expression were small duct type iCCAs. Nestin-positive small duct type iCCAs were characterized by a higher histological grade, compared to Nestin-negative small duct type iCCAs (p < 0.01). Nestin-positive small duct type iCCAs tended to have 2 or more genetic alterations, but there was no statistic difference (p > 0.05).
    Conclusion: Different nestin expression may reflect differences between small duct type iCCA and large duct type/extrahepatic CCA and may be a useful diagnostic marker for small duct type iCCAs.
    MeSH term(s) Humans ; Diagnosis, Differential ; Nestin ; Cholangiocarcinoma/genetics ; Bile Ducts, Intrahepatic/pathology ; Bile Duct Neoplasms/genetics
    Chemical Substances Nestin
    Language English
    Publishing date 2023-12-22
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 391889-0
    ISSN 1618-0631 ; 0344-0338
    ISSN (online) 1618-0631
    ISSN 0344-0338
    DOI 10.1016/j.prp.2023.155061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud III Zs.20: Show issues Location:
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  6. Article ; Online: Pre-invasive intraductal papillary neoplasm of the pancreatobiliary system.

    Nakanuma, Yasuni

    Clinics and research in hepatology and gastroenterology

    2016  Volume 40, Issue 2, Page(s) 133–135

    MeSH term(s) Bile Duct Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/pathology ; Humans ; Neoplasm Invasiveness ; Pancreatic Neoplasms/pathology
    Language English
    Publishing date 2016-04
    Publishing country France
    Document type Editorial
    ZDB-ID 2594333-9
    ISSN 2210-741X ; 2210-7401
    ISSN (online) 2210-741X
    ISSN 2210-7401
    DOI 10.1016/j.clinre.2015.12.005
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  7. Article ; Online: Polypoid invasive carcinoma of bile duct: report of four cases.

    Nakanuma, Yasuni / Nomura, Yoshikatsu / Watanabe, Hiroyuki / Terada, Takuro

    Clinical journal of gastroenterology

    2022  Volume 15, Issue 3, Page(s) 630–634

    Abstract: Recently, "polypoid invasive carcinoma (PICA)" showing grossly visible polypoid, invasive carcinoma with no adenoma component was proposed as a neoplastic polyp of the gallbladder. Herein, we report four cases of PICA of the bile duct. PICA cases of bile ...

    Abstract Recently, "polypoid invasive carcinoma (PICA)" showing grossly visible polypoid, invasive carcinoma with no adenoma component was proposed as a neoplastic polyp of the gallbladder. Herein, we report four cases of PICA of the bile duct. PICA cases of bile duct showed single, sessile polypoid growth grossly, and polypoid components were composed of invasive carcinoma of papillary/tubular patterns with active desmoplasia, and invaded directly and continuously into the bile duct wall and periductal tissue. While PICA and other intraductal papillary neoplasm of bile duct (IPNB) shared several features, PICA showed an invasive carcinoma growing in the duct lumen and also invading into the bile duct wall, thus different from IPNB which is the intraluminal polypoid, preinvasive epithelial neoplasia with back-to-back epithelial units. Taken together, PICA and IPNB could be differentiated from each other.
    MeSH term(s) Bile Duct Neoplasms/diagnostic imaging ; Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/surgery ; Bile Ducts/pathology ; Carcinoma ; Carcinoma, Papillary/pathology ; Common Bile Duct/pathology ; Humans
    Language English
    Publishing date 2022-03-25
    Publishing country Japan
    Document type Case Reports ; Journal Article
    ZDB-ID 2429411-1
    ISSN 1865-7265 ; 1865-7257
    ISSN (online) 1865-7265
    ISSN 1865-7257
    DOI 10.1007/s12328-022-01626-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Highlights of topic "new trends on pathology of cholangiocarcinoma".

    Nakanuma, Yasuni

    Journal of hepato-biliary-pancreatic sciences

    2014  Volume 21, Issue 7, Page(s) 439–440

    MeSH term(s) Bile Duct Neoplasms/pathology ; Bile Ducts, Intrahepatic/pathology ; Cholangiocarcinoma/pathology ; Humans
    Language English
    Publishing date 2014-07
    Publishing country Japan
    Document type Editorial
    ZDB-ID 2536236-7
    ISSN 1868-6982 ; 1868-6974
    ISSN (online) 1868-6982
    ISSN 1868-6974
    DOI 10.1002/jhbp.79
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4024: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Book: Expression profiles of MUC mucins and trefoil factor family (TFF) peptides in the intrahepatic biliary system

    Sasaki, Motoko / Ikeda, Hiroko / Nakanuma, Yasuni

    physiological distribution and pathological significance

    (Progress in histochemistry and cytochemistry ; 42,2)

    2007  

    Author's details Motoko Sasaki ; Hiroko Ikeda ; Yasuni Nakanuma
    Series title Progress in histochemistry and cytochemistry ; 42,2
    Collection
    Language English
    Size S. 61 - 110 : Ill., graph. Darst.
    Publisher Elsevier
    Publishing place Amsterdam u.a.
    Publishing country Netherlands
    Document type Book
    HBZ-ID HT015230278
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    Se 23 -42,2- verfügbar in Königswinter Königswinter

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  10. Article ; Online: Primary biliary cirrhosis: is there still a place for histological evaluation?

    Nakanuma, Yasuni

    Clinics and research in hepatology and gastroenterology

    2014  Volume 38, Issue 1, Page(s) e1–2

    MeSH term(s) Bile Ducts/pathology ; Cholestasis/pathology ; Female ; Humans ; Liver/pathology ; Liver Cirrhosis, Biliary/classification ; Liver Cirrhosis, Biliary/pathology ; Male ; Pathology, Clinical/methods
    Language English
    Publishing date 2014-02
    Publishing country France
    Document type Comment ; Letter
    ZDB-ID 2594333-9
    ISSN 2210-741X ; 2210-7401
    ISSN (online) 2210-741X
    ISSN 2210-7401
    DOI 10.1016/j.clinre.2013.07.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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