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      Hematologic markers of distant metastases and poor prognosis in gynecological cancers

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          Abstract

          Background

          Despite the recent progress in the development of anti-cancer drugs, the treatment of metastatic tumors is usually ineffective. The systemic inflammatory response performs key roles in different stages of the carcinogenesis process including metastasis. The high neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were found to be associated with poor survival rates in the majority of solid tumors. However, only a few studies were conducted to further investigate this association in patients with advanced gynecological cancers.

          Methods

          Clinical data from 264 patients with FIGO stage III and IV gynecological (endometrial, ovarian and cervical) cancers treated at King Hussein Cancer Center (Amman-Jordan) from 2006 to 2012 were retrospectively reviewed. We examined the association between absolute neutrophil count (ANC), absolute monocyte count (AMC), MLR, PLR, and NLR with distant metastases, overall survival and event-free survival in gynecological cancers. For survival analysis, Receiver Operating Characteristic (ROC) curve analysis was operated to determine the optimal cutoff values.

          Results

          Patients with high baseline NLR (≥4.1) had more baseline distant metastases than patients with low baseline NLR (< 4.1), ( p-value 0.045). Patients with high baseline AMC (≥560) had more distant metastases in comparison to patients with low baseline AMC (< 560), ( p-value 0.040). Furthermore, Patients with high baseline PLR (≥0.3) had more distant metastases in comparison to patients with low baseline PLR (< 0.3), ( p-value 0.025). Additionally, patients with high baseline ANC (≥5700) had worse overall survival compared to the patients with low baseline ANC (< 5700), ( p-value 0.015). Also, patients with high baseline AMC (≥490) had worse overall survival compared to the patients with low baseline AMC (< 490), ( p-value 0.044).

          Conclusion

          Different hematologic markers obtained from a cheap test (CBC) could potentially be used to predict the presence of distant metastases thus used as prognostic indices in gynecological cancers.

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          Most cited references19

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          Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma

          Primary cutaneous melanoma is often infiltrated lymphocytes that provide the opportunity to study what may be the local immunologic reaction to the tumor and to correlate the presence of these lymphocytes with overall survival. In an attempt to delineate the histologic diagnostic criteria, to classify different categories of lymphocytic infiltrates, previously described by Elder et al. at brisk, nonbrisk, and absent, and to verify their prognostic significance, we reviewed 285 consecutive cases of primary cutaneous melanomas (American Joint Committee on Cancer Stage I and II). In addition to clinical variables (age, sex, and location of tumor) and the presence of tumor infiltrating lymphocytes in the vertical growth phase, the histopathologic attributes reviewed included mitotic rate, thickness, and regression. The results were derived from independent histopathologic review by two pathologists (C.G.C., M.C.M., Jr.) on separate occasions. A multivariate analysis of survival was performed with the Cox's regression model. The 5- and 10-year rates for melanoma with a vertical growth phase and a brisk infiltrate were 77% and 55%, respectively. For tumors with a nonbrisk infiltrate, the 5- and 10-year survival rates were 53% and 45%, respectively, and for tumors with absent tumor infiltrating lymphocytes, the 5- and 10-year survival rates were 37% and 27%, respectively. Mitotic index, thickness, and tumor infiltrating lymphocytes were statistically (univariate analysis) significant prognostic factors (P = 0.003, 0.000001, 0.0003, respectively), whereas the presence or absence of regression is not. In the univariate statistical analysis, the sex of patients and site of melanoma also were statistically significant (P = 0.00001 and 0.002 respectively), whereas age (P = 0.98) was not statistically significant. The multivariate analysis of thickness, mitotic rate, and tumor infiltrating lymphocytes showed that thickness and presence tumor infiltrating lymphocytes were significant and independent histologic prognostic factors. With regard to the clinical factors, sex retained its independent prognostic significance. The histologic characteristics of melanoma with vertical growth phase (brisk, nonbrisk, and absent) are exemplified. We demonstrated that when categories of tumor infiltrating lymphocytes are strictly defined, they indeed have very strong predictive value for primary cutaneous melanomas with a vertical growth phase. This work confirms the work of Clark et al. and fully illustrates the brisk, nonbrisk, and absent categories of infiltration. Finally, a multivariate analysis comparing thickness, mitotic rate and presence of tumor infiltrating lymphocytes showed that only thickness and presence of tumor infiltrating lymphocytes are significant and independent positive histologic prognostic factors.
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            Advances in diagnosis and treatment of metastatic cervical cancer

            Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.
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              Inflammasomes and Cancer.

              Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota. Activation of the inflammasome and IL18 signaling pathways is largely protective in colitis-associated colorectal cancer, whereas excessive inflammation driven by the inflammasome or the IL1 signaling pathways promotes breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis in a context-dependent manner. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. In this review, we explore the crossroads between inflammasomes and the development of various tumors and discuss possible therapeutic values in targeting the inflammasome for the prevention and treatment of cancer. Cancer Immunol Res; 5(2); 94-99. ©2017 AACR.
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                Author and article information

                Contributors
                Osamashawer58@gmail.com
                Mohshawer1@gmail.com
                Naderhirmas@gmail.com
                Abdallahouri1995@gmail.com
                A.massad97@yahoo.com
                Bilal.sibai@hotmail.com
                Lalasultan@hotmail.com
                Hahammo@gmail.com
                Mamoon1995@hotmail.com
                Yasmeenshebli@hotmail.com
                +962-6-5300-460 , Mhussaini@khcc.jo
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                12 February 2019
                12 February 2019
                2019
                : 19
                : 141
                Affiliations
                [1 ]ISNI 0000 0001 2174 4509, GRID grid.9670.8, University of Jordan School of Medicine, ; Amman, Jordan
                [2 ]Prince Hamzah Hospital, Amman, Jordan
                [3 ]ISNI 0000 0001 1847 1773, GRID grid.419782.1, King Hussein Cancer Center, ; Amman, Jordan
                [4 ]ISNI 0000 0001 1847 1773, GRID grid.419782.1, Department of Pathology and Laboratory Medicine, , King Hussein Cancer Center, ; Amman, 11941 Jordan
                Author information
                http://orcid.org/0000-0001-6392-150X
                Article
                5326
                10.1186/s12885-019-5326-9
                6373103
                30755184
                c9f1726d-0204-4042-b90e-3abc30242959
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 May 2018
                : 28 January 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                gynecological cancer. neutrophil-lymphocyte ratio. distant metastases. survival

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