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      Lymphatic Drainage Mapping with Indirect Lymphography for Canine Mammary Tumors

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          Abstract

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          Mammary gland tumours are the most common canine neoplasms. They account for 25–50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35–70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. As mammary gland tumors mainly spread by lymphatic vessels invasion, conceptually, distant metastasis should not be present if the SLN does not have evidence of a tumor burden. In the present study, an indirect lymphography was used for sentinel lymph node mapping in a cohort of 14 adult female dogs with 24 mammary tumors involving the third to the fifth mammary gland. Contrast was injected around the mammary tumor, and lymph nodes that picked up the contrast were visible after 24 h. The results of this study indicate that the lymph drainage pattern of the neoplastic mammary gland may be different for each tumor. The knowledge of the SLN of the neoplastic mammary glands should be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis.

          Abstract

          Mammary gland tumors are the most common canine neoplasms. They account for 25–50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35–70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. The aim of this study is to investigate the SLN with indirect lymphography for a mammary tumor in dogs. The knowledge of the precise drainage pattern and SLN of the neoplastic mammary glands would provide clinically relevant information to the surgeon and to the oncologist, and it would be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis.

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          Most cited references39

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          Regulation of angiogenesis via vascular endothelial growth factor receptors.

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            Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma.

            The sentinel node hypothesis assumes that a primary tumor drains to a specific lymph node in the regional lymphatic basin. To determine whether the sentinel node is indeed the node most likely to harbor an axillary metastasis from breast carcinoma, the authors used cytokeratin immunohistochemical staining (IHC) to examine both sentinel and nonsentinel lymph nodes. From February 1994 through October 1995, patients with breast cancer were staged with sentinel lymphadenectomy followed by completion level I and II axillary dissection. If the sentinel node was free of metastasis by hematoxylin and eosin staining (H&E), then sentinel and nonsentinel nodes were examined with IHC. The 103 patients had a median age of 55 years and a median tumor size of 1.8 cm (58.3% T1, 39.8% T2, and 1.9% T3). A mean of 2 sentinel (range, 1-8) and 18.9 nonsentinel (range, 7-37) nodes were excised per patient. The H&E identified 33 patients (32%) with a sentinel lymph node metastasis and 70 patients (68%) with tumor-free sentinel nodes. Applying IHC to the 157 tumor-free sentinel nodes in these 70 patients showed an additional 10 tumor-involved nodes, each in a different patient. Thus, 10 (14.3%) of 70 patients who were tumor-free by H&E actually were sentinel node-positive, and the IHC lymph node conversion rate from sentinel node-negative to sentinel node-positive was 6.4% (10/157). Overall, sentinel node metastases were detected in 43 (41.8%) of 103 patients. In the 60 patients whose sentinel nodes were metastasis-free by H&E and IHC, 1087 nonsentinel nodes were examined at 2 levels by IHC and only 1 additional tumor-positive lymph node was identified. Therefore, one H&E sentinel node-negative patient (1.7%) was actually node-positive (p < 0.0001), and the nonsentinel IHC lymph node conversion rate was 0.09% (1/1087; p < 0.0001). If the sentinel node is tumor-free by both H&E and IHC, then the probability of nonsentinel node involvement is <0.1%. The true false-negative rate of this technique using multiple sections and IHC to examine all nonsentinel nodes for metastasis is 0.97% (1/103) in the authors' hands. The sentinel lymph node is indeed the most likely axillary node to harbor metastatic breast carcinoma.
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              Pathologic findings from the National Surgical Adjuvant Breast Project protocol B-06. 10-year pathologic and clinical prognostic discriminants.

              Prognostic pathologic and clinical features for 10-year survival were determined from 22 pathologic and 5 clinical variables encountered in 1090 node-negative and 651 node-positive patients enrolled in NSABP protocol B-06. All factors were first screened univariately. Those exhibiting P values < 0.01 were entered into multivariate Cox regression models. The model with the best fit consisted of 951 negative-node and 496 node-positive patients. Better survival in node-negative patients was noted for whites rather than blacks, for patients with favorable tumor types (tubular, mucinous, papillary) rather than intermediate (lobular invasive, classical medullary, and not otherwise specified [NOS] combinations) or unfavorable forms (NOS pure and atypical medullary), and for tumors with good rather than poor nuclear grade. Number of nodal metastases, degree of tumor elastosis, and patient age younger than 40 years of age and 65 years of age and older in addition to nuclear grade and race were found significant for node-positive patients. Relative risks for combinations of these prognostic factors were multiplicative. The prognostic factors for node-negative patients were similar to those observed for this cohort at 8 years. Some differences noted between patients of both nodal groups in NSABP B-04 and B-06 may be related to selection requirements in the latter and hence different patient characteristics or more speculatively a change in tumor biology.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Animals (Basel)
                Animals (Basel)
                animals
                Animals : an Open Access Journal from MDPI
                MDPI
                2076-2615
                13 April 2021
                April 2021
                : 11
                : 4
                : 1115
                Affiliations
                [1 ]Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy; fcollivignarelli@ 123456unite.it (F.C.); ifalerno@ 123456unite.it (I.F.); fdelsignore@ 123456unite.it (F.D.S.); fsimeoni@ 123456unite.it (F.S.); acarluccio@ 123456unite.it (A.C.); mvignoli@ 123456unite.it (M.V.)
                [2 ]School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; patsikm@ 123456vet.auth.gr
                [3 ]Clinica Veterinaria Val Musone, 60027 Osimo (AN), Italy; jacopogianf@ 123456libero.it
                [4 ]Clinica Veterinaria Pet Care, 40133 Bologna, Italy; terragni.rossella@ 123456gmail.com
                [5 ]Clinica Veterinaria Riviera Vet, 63066 Grottammare (AP), Italy; valeria.attorri@ 123456gmail.com
                Author notes
                [* ]Correspondence: rtamburro@ 123456unite.it (R.T.); gaste@ 123456unite.it (G.A.); Tel.: +39-(0)-861-266835 (R.T.); +39-(0)-861-266884 (G.A.)
                Author information
                https://orcid.org/0000-0001-6198-163X
                https://orcid.org/0000-0001-5308-4402
                https://orcid.org/0000-0002-4981-4051
                Article
                animals-11-01115
                10.3390/ani11041115
                8070006
                33924625
                2cf433e9-7971-450d-ab9d-0da3d2305c14
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 16 March 2021
                : 11 April 2021
                Categories
                Article

                sentinel lymph node,mammary gland tumors,indirect lymphography

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