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      Micrometastases in Sentinel Lymph Nodes Represent a Significant Negative Prognostic Factor in Early-Stage Cervical Cancer: A Single-Institutional Retrospective Cohort Study

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          Abstract

          The data on the prognostic significance of low volume metastases in lymph nodes (LN) are inconsistent. The aim of this study was to retrospectively analyze the outcome of a large group of patients treated with sentinel lymph node (SLN) biopsy at a single referral center. Patients with cervical cancer, stage T1a-T2b, common tumor types, negative LN on preoperative staging, treated by primary surgery between 01/2007 and 12/2016, with at least unilateral SLN detection were included. Patients with abandoned radical surgery due to intraoperative SLN positivity detected by frozen section were excluded. All SLNs were postoperatively processed by an intensive protocol for pathological ultrastaging. Altogether, 226 patients were analyzed. Positive LN were detected in 38 (17%) cases; macrometastases (MAC), micrometastases (MIC), isolated tumor cells (ITC) in 14, 16, and 8 patients. With the median follow-up of 65 months, 22 recurrences occurred. Disease-free survival (DFS) reached 90% in the whole group, 93% in LN-negative cases, 89% in cases with MAC, 69% with MIC, and 87% with ITC. The presence of MIC in SLN was associated with significantly decreased DFS and OS. Patients with MIC and MAC should be managed similarly, and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer.

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          Most cited references40

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          Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer

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            Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

            There were 732 evaluable patients with primary, previously untreated, histologically confirmed stage I squamous carcinoma of the cervix with greater than or equal to 3-mm invasion. Of these, 645 had no gross disease beyond the cervix/uterus, had negative paraaortic lymph nodes, and had undergone a radical hysterectomy with pelvic lymphadenectomy. The 3-year disease-free interval (DFIs) for the 545 patients with negative pelvic nodes was 85.6%, and for the 100 with positive pelvic nodes, 74.4%. A large number of pelvic nodes involved with tumor was not correlated with a poorer prognosis; the DFIs were 72.1, 86.4, and 64.6% for one, two, and three or more positive pelvic nodes, respectively. DFI correlated strongly with depth of tumor invasion, both in absolute terms (mm) and infractional thirds. The DFI was 94.6% for less than or equal to 5 mm, 86.0% for 6-10 mm, 75.2% for 11-15 mm, 71.5% for 16-20 mm, and 59.5% greater than or equal to 21 mm. In fractional terms, the DFI was 94.1% for superficial third, 84.5% for middle third, and 73.6% for deep third invasion. With respect to clinical tumor size, the DFIs were 94.8, 88.1, and 67.6% for occult, less than or equal to 3 cm, and greater than 3 cm, respectively. The DFI was 77.0% for those with positive capillary-lymphatic spaces (CLS) and 88.9% for those with negative CLS. Tumor grade and parametrial status correlated with DFI. DFI was not significantly different for age, disease status of the surgical margins, tumor description (e.g., exophytic), quadrant involved with tumor, uterine extension, and keratinizing status of tumor cells. Clinical tumor size, CLS, and depth of tumor invasion were independent prognostic factors.
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              Classification of radical hysterectomy.

              Since the first publications about surgery for cervical cancer, many radical procedures that accord with different degrees of radicality have been described and done. Here, we propose a basis for a new and simple classification for cervical-cancer surgery, taking into account the curative effect of surgery and adverse effects, such as bladder dysfunction. The international anatomical nomenclature is used where it applies. For simplification, the classification is based only on lateral extent of resection. We describe four types of radical hysterectomy (A-D), adding when necessary a few subtypes that consider nerve preservation and paracervical lymphadenectomy. Lymph-node dissection is considered separately: four levels (1-4) are defined according to corresponding arterial anatomy and radicality of the procedure. The classification applies to fertility-sparing surgery, and can be adapted to open, vaginal, laparoscopic, or robotic surgery. In the future, internationally standardised description of techniques for communication, comparison, clinical research, and quality control will be a basic part of every surgical procedure.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                31 May 2020
                June 2020
                : 12
                : 6
                : 1438
                Affiliations
                [1 ]Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, 128 00 Prague, Czech Republic; kocianroman@ 123456seznam.cz (R.K.); Jiri.Slama@ 123456vfn.cz (J.S.); daniela.fischerova@ 123456seznam.cz (D.F.); ena.german@ 123456gmail.com (A.G.); fruhauffilip@ 123456centrum.cz (F.F.); Lukas.Dostalek@ 123456vfn.cz (L.D.); Tereza.Ballaschova@ 123456vfn.cz (T.B.)
                [2 ]Department of Radiology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, 128 00 Prague, Czech Republic; Andrea.Burgetova@ 123456vfn.cz
                [3 ]Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic; dusek@ 123456iba.muni.cz (L.D.); jarkovsky@ 123456iba.muni.cz (J.J.)
                [4 ]Institute of Health Information and Statistics of the Czech Republic, 128 01 Prague, Czech Republic; Zouharova@ 123456iba.muni.cz
                [5 ]Department of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, 128 00 Prague, Czech Republic; pavel.dundr@ 123456vfn.cz (P.D.); kristyna.nemejcova@ 123456vfn.cz (K.N.)
                Author notes
                [* ]Correspondence: dc@ 123456davidcibula.cz ; Tel.: +420-224967451
                Author information
                https://orcid.org/0000-0002-5896-4158
                https://orcid.org/0000-0001-9340-9320
                https://orcid.org/0000-0001-6387-9356
                Article
                cancers-12-01438
                10.3390/cancers12061438
                7352782
                32486512
                389d2fe8-6c0a-4034-8c17-d43a742ffe83
                © 2020 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 April 2020
                : 28 May 2020
                Categories
                Article

                micrometastasis,isolated tumor cells,sentinel lymph node,cervical cancer,pathological ultrastaging,prognostic parameters,risk of recurrence

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