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  1. Book: Endocrine Pathology

    Uccella, Silvia / La Rosa, Stefano

    (Encyclopedia of Pathology)

    2021  

    Abstract: This book covers the complete field of endocrine pathology – from Acidophil Stem Cell Adenoma to Zona Reticularis. The alphabetically arranged entries, each of which provides a detailed description of a specific pathological disease pattern, allow ... ...

    Author's details Stefano La Rosa is currently associate professor of pathology at the University of Insubria of Varese (Italy) and senior consultant of pathology at the University Hospital of Varese. From 2016 to 2021 he served as associate professor of Pathology at the University of Lausanne (Switzerland) and as senior consultant of pathology at the University Hospital of Lausanne (CHUV). However, his academic and clinical activity started in Italy in 1997 as consultant of pathology at the University Hospital of Varese (Italy) and assistant professor of pathology at the University of Insubria. He obtained his medical degree in 1992 and his specialization in Pathology in 1996 at the University of Pavia, Italy. Prof. La Rosa has an expertise in endocrine pathology, with special reference to digestive neuroendocrine neoplasms, pituitary and thyroid pathology, and diabetes mellitus. His research activity has mainly been focused on the study of prognostic biomarkers in neuroendocrineneoplasms and on pan
    Series title Encyclopedia of Pathology
    Abstract This book covers the complete field of endocrine pathology – from Acidophil Stem Cell Adenoma to Zona Reticularis. The alphabetically arranged entries, each of which provides a detailed description of a specific pathological disease pattern, allow readers to quickly and easily find the information they need. -- --
    Keywords MHMO015 ; MHMC050 ; MHMB030 ; Pituitary ; thyroid ; Parathyroid ; Adrenal gland ; gonads ; Inherited tumor syndromes ; Neuroendocrine Neoplasms ; Paraganglia ; Thyroid ; Gonads ; Neuroendocrine neoplasms
    Language English
    Size 876 p.
    Edition 1
    Publisher Springer International Publishing
    Document type Book
    Note PDA Manuell_18
    Format 183 x 260 x 52
    ISBN 9783030623449 ; 3030623440
    Database PDA

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  2. Article ; Online: Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?

    Uccella, Silvia

    Endocrine pathology

    2024  

    Abstract: In the last two decades, the increasing availability of technologies for molecular analyses has allowed an insight in the genomic alterations of neuroendocrine neoplasms (NEN) of the gastrointestinal tract and pancreas. This knowledge has confirmed, ... ...

    Abstract In the last two decades, the increasing availability of technologies for molecular analyses has allowed an insight in the genomic alterations of neuroendocrine neoplasms (NEN) of the gastrointestinal tract and pancreas. This knowledge has confirmed, supported, and informed the pathological classification of NEN, clarifying the differences between neuroendocrine carcinomas (NEC) and neuroendocrine tumors (NET) and helping to define the G3 NET category. At the same time, the identification genomic alterations, in terms of gene mutation, structural abnormalities, and epigenetic changes differentially involved in the pathogenesis of NEC and NET has identified potential molecular targets for precision therapy. This review critically recapitulates the available molecular features of digestive NEC and NET, highlighting their correlates with pathological aspects and clinical characteristics of these neoplasms and revising their role as predictive biomarkers for targeted therapy. In this context, the feasibility and applicability of a molecular classification of gastrointestinal and pancreatic NEN will be explored.
    Language English
    Publishing date 2024-03-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1033267-4
    ISSN 1559-0097 ; 1046-3976
    ISSN (online) 1559-0097
    ISSN 1046-3976
    DOI 10.1007/s12022-024-09807-2
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  3. Article ; Online: The classification of neuroendocrine neoplasms of the breast and its clinical relevance.

    Uccella, Silvia

    Virchows Archiv : an international journal of pathology

    2021  Volume 481, Issue 1, Page(s) 3–12

    Abstract: Neuroendocrine neoplasms of the breast (Br-NENs) are rare tumors of the mammary gland. Their definition and classification have been a matter of discussion for more than half a century, as they present some degree of overlap with other malignancies in ... ...

    Abstract Neuroendocrine neoplasms of the breast (Br-NENs) are rare tumors of the mammary gland. Their definition and classification have been a matter of discussion for more than half a century, as they present some degree of overlap with other malignancies in the mammary gland. The recent evolutions in the understanding of the pathogenesis of neuroendocrine neoplasms (NENs) as well as the novel tools in the diagnostic arsenal of the pathologists, and a better correlation with clinical data, have led to improved classification schemes for these entities, beginning from those arising in digestive and thoracic organs. These new classification concepts have been recently expanded to NENs arising in every anatomical site, with the proposal of a common classification framework that has been applied in the 5th edition of the WHO classification of tumors. These concepts include the recognition of two distinct families of NENs (neuroendocrine tumors, NETs, and neuroendocrine carcinomas, NECs), the identification of mixed neuroendocrine/non-neuroendocrine neoplasms, and the application of definite morphological and immunohistochemical criteria for the diagnosis of NENs. The last WHO classification of Br-NENs, however, still seems to leave several unanswered questions and unmet needs in the understanding of diagnostic and clinical features of these entities. This review will critically revise the current classification of Br-NENs, underlining its lights and shadows and focusing on the identification of diagnostic histopathological criteria that can help the univocal recognition of Br-NET, Br-NEC, and Br-MiNEN.
    MeSH term(s) Carcinoma, Neuroendocrine/diagnosis ; Carcinoma, Neuroendocrine/pathology ; Humans ; Infant, Newborn ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/pathology ; Pancreatic Neoplasms/pathology
    Language English
    Publishing date 2021-10-26
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-021-03223-1
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  4. Article ; Online: Intraoperative Findings of Duplicated Inferior Vena Cava during Laparoscopic Para-Aortic Lymphadenectomy.

    Uccella, Stefano / Caraffini, Andrea / Zorzato, Pier Carlo / Garzon, Simone

    Journal of minimally invasive gynecology

    2024  

    Language English
    Publishing date 2024-04-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2186934-0
    ISSN 1553-4669 ; 1553-4650
    ISSN (online) 1553-4669
    ISSN 1553-4650
    DOI 10.1016/j.jmig.2024.04.018
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  5. Article ; Online: PD-L1 expression, tumor-infiltrating lymphocytes, and mismatch repair proteins status in digestive neuroendocrine neoplasms: exploring their potential role as theragnostic and prognostic biomarkers.

    Multone, Eléonore / La Rosa, Stefano / Sempoux, Christine / Uccella, Silvia

    Virchows Archiv : an international journal of pathology

    2024  

    Abstract: Theragnostic biomarkers are still needed to select patients with digestive neuroendocrine neoplasms (NENs) for an optimal management. The PD-1/PD-L1 pathway plays a pivotal role in T cells activation and host immune response to cancer and PD-L1 ... ...

    Abstract Theragnostic biomarkers are still needed to select patients with digestive neuroendocrine neoplasms (NENs) for an optimal management. The PD-1/PD-L1 pathway plays a pivotal role in T cells activation and host immune response to cancer and PD-L1 expression in tumor and/or immune cells is used to identify patients who would benefit of treatment with immune checkpoint inhibitors. However, its role as a biomarker is still unclear in digestive NENs. We investigated PD-L1 expression in 68 well-characterized digestive NENs (32 NETs, 32 NECs and 4 MiNENs) and TPS and CPS scores were calculated. In addition, tumor infiltrating T-lymphocytes and mismatch repair protein expression (MMR) were evaluated. All results were correlated with clinicopathological features. PD-L1 expression was higher in NECs than in NETs: TPS > 1% and/or CPS > 1 were observed in 16% of NETs, 68.8% of NECs and 50% of MiNENs (p: 0.05). The mean TPS score in positive cases was 6.3% in NETs, 16.2% in NECs and 5% in MiNENs. The CPS score was 4.8 in NETs, 8.1 in NECs and 6 in MiNENs. MMR-deficient neoplasms were more frequently observed in NECs than in NETs (p: < 0.05) as well as intra-tumor immune infiltration (p: 0.00001). No correlation between PD-L1 expression and survival or other clinicopathological parameters was observed. Our results suggest that treatment with immune checkpoint inhibitors may have a potential role only in selected cases, mainly in NECs and MiNENs.
    Language English
    Publishing date 2024-05-21
    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/s00428-024-03825-5
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  6. Article ; Online: The Unique Importance of Differentiation and Function in Endocrine Neoplasia.

    Asa, Sylvia L / Uccella, Silvia / Tischler, Arthur

    Endocrine pathology

    2023  Volume 34, Issue 4, Page(s) 382–392

    Abstract: The assessment of cell differentiation in endocrine neoplasms involves not only the identification of a cell's structure and expression of specific transcription factors which regulate that cell, but also the identification of hormones and/or enzymes ... ...

    Abstract The assessment of cell differentiation in endocrine neoplasms involves not only the identification of a cell's structure and expression of specific transcription factors which regulate that cell, but also the identification of hormones and/or enzymes involved in hormone synthesis. The importance of this functional characterization is emphasized by the fact that the hormones serve as biomarkers for clinical surveillance to identify persistence, recurrence, or progression of disease. Sometimes, unusual patterns of hormone expression lead to unexpected clinical signs and symptoms. Loss of differentiated hormone production can be a sign of dedifferentiation as a tumor becomes more aggressive. In addition to prognostic information, cell differentiation can be predictive, since differentiated endocrine cells express targets for therapy, such as the sodium iodide symporter in thyroid cancers and somatostatin receptors in neuroendocrine tumors. The salient features of differentiation in the three main types of endocrine cells can be used to determine prognosis and to tailor management of patients with endocrine neoplasms.
    MeSH term(s) Humans ; Endocrine Gland Neoplasms/diagnosis ; Thyroid Neoplasms/diagnosis ; Thyroid Neoplasms/pathology ; Prognosis ; Cell Differentiation ; Hormones/metabolism
    Chemical Substances Hormones
    Language English
    Publishing date 2023-04-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1033267-4
    ISSN 1559-0097 ; 1046-3976
    ISSN (online) 1559-0097
    ISSN 1046-3976
    DOI 10.1007/s12022-023-09762-4
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  7. Article ; Online: Reply to Research on intrauterine manipulators for endometrial cancer: attention to study-level characteristics.

    Garzon, Simone / Zorzato, Pier Carlo / Uccella, Stefano

    American journal of obstetrics and gynecology

    2023  Volume 230, Issue 4, Page(s) e58

    MeSH term(s) Female ; Humans ; Endometrial Neoplasms/surgery ; Hysterectomy
    Language English
    Publishing date 2023-12-07
    Publishing country United States
    Document type Letter
    ZDB-ID 80016-8
    ISSN 1097-6868 ; 0002-9378
    ISSN (online) 1097-6868
    ISSN 0002-9378
    DOI 10.1016/j.ajog.2023.12.005
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  8. Article ; Online: Regarding "Utility of Routine Postoperative Examination for Detecting Vaginal Cuff Dehiscence After Total Laparoscopic Hysterectomy".

    Uccella, Stefano / Casprini, Chiara / Bertoli, Francesca / Zorzato, Pier Carlo / Garzon, Simone / Galli, Liliana

    Journal of minimally invasive gynecology

    2024  Volume 31, Issue 5, Page(s) 464

    MeSH term(s) Humans ; Female ; Surgical Wound Dehiscence/etiology ; Laparoscopy/adverse effects ; Hysterectomy/adverse effects ; Hysterectomy/methods ; Vagina/surgery
    Language English
    Publishing date 2024-02-10
    Publishing country United States
    Document type Letter
    ZDB-ID 2186934-0
    ISSN 1553-4669 ; 1553-4650
    ISSN (online) 1553-4669
    ISSN 1553-4650
    DOI 10.1016/j.jmig.2024.01.023
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  9. Article ; Online: Response: Clinician perspectives on hysterectomy versus uterine preservation in pelvic organ prolapse surgery: A systematic review and meta-analysis.

    Porcari, Irene / Zorzato, Pier Carlo / Bosco, Mariachiara / Garzon, Simone / Uccella, Stefano

    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics

    2024  

    Language English
    Publishing date 2024-05-17
    Publishing country United States
    Document type Letter
    ZDB-ID 80149-5
    ISSN 1879-3479 ; 0020-7292
    ISSN (online) 1879-3479
    ISSN 0020-7292
    DOI 10.1002/ijgo.15693
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  10. Article ; Online: Pancreatic neuroendocrine tumor progression and resistance to everolimus: the crucial role of NF-kB and STAT3 interplay.

    Vitali, E / Valente, G / Panzardi, A / Laffi, A / Zerbi, A / Uccella, S / Mazziotti, G / Lania, A

    Journal of endocrinological investigation

    2023  Volume 47, Issue 5, Page(s) 1101–1117

    Abstract: Purpose: The finding of mTOR overactivation in patients affected by pancreatic neuroendocrine tumors (Pa-NETs) led to their treatment with the mTOR inhibitor everolimus. Unfortunately, the efficacy of everolimus is restricted by the occurrence of ... ...

    Abstract Purpose: The finding of mTOR overactivation in patients affected by pancreatic neuroendocrine tumors (Pa-NETs) led to their treatment with the mTOR inhibitor everolimus. Unfortunately, the efficacy of everolimus is restricted by the occurrence of resistance. The mechanisms leading to Pa-NETs' progression and resistance are not well understood. Notably, chronic inflammation is implicated in NET development. NF-kB is involved in inflammation and drug resistance mechanisms through the activation of several mediators, including STAT3. In this respect, NF-κB and STAT3 interaction is implicated in the crosstalk between inflammatory and tumor cells.
    Methods: We investigated the expression of NF-kB in different Pa-NETs by RT-qPCR and immunohistochemistry. Then, we studied the role of NF-κB and STAT3 interplay in QGP-1 cells. Subsequently, we assessed the impact of NF-κB and STAT3 inhibitors in QGP-1 cell proliferation and spheroids growth. Finally, we evaluated the implication of the NF-kB pathway in everolimus-resistant Pa-NET cells.
    Results: We found that the increased NF-kB expression correlates  with a higher grade in Pa-NETs. The activation of the STAT3 pathway induced by TNFα is mediated by NF-kB p65. NF-kB p65 and STAT3 inhibitors decrease QGP-1 viability, spheroids growth, and Pa-NETs cell proliferation. These effects are maintained in everolimus-resistant QGP-1R cells. Interestingly, we found that NF-kB, STAT3, IL-8, and SOCS3 are overexpressed in QGP-1R compared to QGP-1.
    Conclusion: Since the NF-kB pathway is implicated in Pa-NETs' progression and resistance to everolimus, these data could explain the potential use of NF-kB as a novel therapeutic target in Pa-NET patients.
    MeSH term(s) Humans ; Everolimus/pharmacology ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; STAT3 Transcription Factor/metabolism ; Neuroendocrine Tumors/metabolism ; Neuroendocrine Tumors/drug therapy ; Neuroendocrine Tumors/pathology ; Drug Resistance, Neoplasm ; NF-kappa B/metabolism ; Disease Progression ; Antineoplastic Agents/pharmacology ; Cell Proliferation/drug effects ; Female ; Male ; Middle Aged ; Signal Transduction/drug effects ; Tumor Cells, Cultured ; Cell Line, Tumor ; Aged ; Adult
    Chemical Substances Everolimus (9HW64Q8G6G) ; STAT3 Transcription Factor ; NF-kappa B ; STAT3 protein, human ; Antineoplastic Agents
    Language English
    Publishing date 2023-10-26
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 432272-1
    ISSN 1720-8386 ; 0391-4097 ; 1121-1369
    ISSN (online) 1720-8386
    ISSN 0391-4097 ; 1121-1369
    DOI 10.1007/s40618-023-02221-1
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