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1.
JAMA ; 322(16): 1570-1579, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638680

RESUMO

Importance: The World Health Organization recommends cryotherapy or loop electrosurgical excision procedure (LEEP) for histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2 or higher regardless of HIV status. Cryotherapy is more feasible in resource-limited settings but may be less effective for women living with HIV. Objective: To evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV. Design, Setting, and Participants: Single-center randomized trial conducted among women with HIV and CIN grade 2 or 3. From June 2011 to September 2016, women with HIV in Kenya underwent cervical screening with Papanicolaou testing and confirmatory biopsy. The final date on which a study procedure was administered was September 7, 2016. Interventions: Women with HIV infection and CIN grade 2 or 3 were randomized 1:1 to receive cryotherapy (n = 200) or LEEP (n = 200) and were followed up every 6 months for 24 months with a Papanicolaou test and confirmatory biopsy. Main Outcome and Measures: The primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period. Results: Among 400 women who were randomized (median age, 37.4 [interquartile range, 31.9-43.8] years), 339 (85%) completed the trial. Over 2 years, 60 women (30%) randomized to cryotherapy had recurrent CIN grade 2 or higher vs 37 (19%) in the LEEP group (relative risk, 1.71 [95% CI, 1.12-2.65]; risk difference, 7.9% [95% CI, 1.9%-14.0%]; P = .01). Adverse events occurred in 40 women (45 events, including change in pathology and death due to other causes) in the cryotherapy group and in 30 women (38 events, including change in pathology and unrelated gynecological complications) in the LEEP group. Conclusions and Relevance: In this single-center study of women with HIV infection and CIN grade 2 or 3, treatment with LEEP compared with cryotherapy resulted in a significantly lower rate of cervical neoplasia recurrence over 24 months. Cost-effectiveness analysis is necessary to determine whether the additional benefit of LEEP represents an efficient use of the additional resources that would be required. Trial Registration: ClinicalTrials.gov Identifier: NCT01298596.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Criocirurgia , Eletrocirurgia , Infecções por HIV/complicações , Neoplasias do Colo do Útero/cirurgia , Adolescente , Adulto , Contagem de Linfócito CD4 , Neoplasia Intraepitelial Cervical/complicações , Neoplasia Intraepitelial Cervical/patologia , Colposcopia , Feminino , Humanos , Incidência , Análise de Intenção de Tratamento , Quênia , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Modelos de Riscos Proporcionais , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Adulto Jovem
2.
Medicine (Baltimore) ; 98(39): e17234, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574835

RESUMO

Locally advanced cervical carcinoma has a poor prognosis. Neoadjuvant chemotherapy (NACT) can reduce tumor size and improve tumor resection rate, but its use in large locally advanced cervical carcinoma is controversial. This study aimed to evaluate the treatment and prognosis of NACT in patients with cervical carcinoma stage IB2 or IIA2.This was a retrospective cohort study of patients who underwent type-C radical surgery and pelvic lymphadenectomy due to cervical carcinoma stage IB2/IIA2 between 2/2014 and 12/2016 at the Second Hospital of Jilin University. The patients were grouped according to whether they received NACT (paclitaxel and a platinum salt) or not. Overall survival (OS) and progression-free survival (PFS) were compared between the 2 groups.Of the 144 patients, 60 (41.7%) received NACT. A total of 119 patients underwent postoperative radiation therapy, of which 97 received radiation therapy alone and 22 received concurrent chemoradiotherapy. The adverse reactions in the NACT group were mainly hematologic toxic reactions, but were tolerated. No grade ≥III adverse reactions were observed. NACT did not significantly affect the PFS (P = .453) and OS (P = .933) between the 2 groups. No factor was found to be independently associated with OS or PFS (all P > .05).Compared with patients who underwent surgery with/without radiotherapy and/or chemotherapy, NACT using paclitaxel and a platinum salt does not improve the prognosis and lymph node metastasis rate of locally advanced cervical carcinoma in Chinese patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Histerectomia/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/mortalidade , China , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Paclitaxel/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
3.
Medicine (Baltimore) ; 98(40): e17301, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577720

RESUMO

The metastasis of cervical carcinoma is associated with the lymphovascular spread. The primary objective of the present study was to determine the prognostic value of lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer in Jilin, China.In this retrospective cohort study, patients with early-stage cervical cancer (stage IB-IIA) at the Second Hospital of Jilin University from February 2014 to December 2016 were included in the analysis. All included participants underwent radical hysterectomy with pelvic lymphadenectomy. LVSI was identified by hematoxylin and eosin (H&E) staining. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Kaplan-Meier curves were used to calculate the patient's survival. Survival was compared using the log-rank test, while risk factors for the prognosis were assessed by Cox regression analysis.The incidence of LVSI was positively associated with the depth of stromal invasion (P = .009) and lymph node metastasis (LNM, P < .001). LVSI is an independent factor that affects OS (P = .009) and PFS (P = .006) in patients with early stage cervical cancer. LNM status is an independent factor that affects postoperative OS (P = .005).The incidence of lymphatic vessel infiltration is positively associated with the depth of stromal invasion and LNM. LVSI is an independent risk factor for the prognosis of early cervical cancer. The results suggest that further large-scale studies are needed to improve the treatment for patients with LVSI.


Assuntos
Metástase Linfática/patologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto , China/epidemiologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/terapia
4.
Pan Afr Med J ; 33: 124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558923

RESUMO

Introduction: high risk HPV is the perpetrator of cervical cancer disease, however screening and vaccination is not included in cervical cancer prevention program within public hospitals in Kenya. This descriptive study assessed the association of specific microbial STI and socio-demographic characteristics and practices with cervical cytomorphologic presentations in regards to pre cervical cancer grades amongst health seeking patients attending the reproductive health clinic of Nakuru County referral hospital, a public hospital under newly devolved health services governance. Methods: a total of 142 patients (AGC/AIS, n=8; HSIL, n=59; LSIL, n=35; controls, n=40) whose median age ranged between 20-70 years were purposively sampled. A structured questionnaire with closed and open ended entries was administered and STI screening including Pap smear examination for cytomorphological profiling done according to revised 2014 Bethesda classification. Associations were established using chi-square and multivariate logistic regression model to determine prediction of cervical atypia manifestations. Results: a majority of the study participants had only primary education or no education in AGC/AIS (63%) and HSIL (73%) relative to LSIL (49%) and controls (53%) (P=0.017). Koilocyte rates were higher in AGC/AIS (25%), HSIL (52%) and LSIL (77%) compared controls (12.5%) (P<0.0001). ASCUS predominated in HSIL (61%) and LSIL (86%), while almost all AGC/AIS had AGCUS (88%). HR HPV 16/18 infection rates were higher in AGC/AIS (100%), HSIL (80%) and LSIL (83%) relative to controls (10%) (P<0.0001), and was associated with higher risk of having AGC/AIS (OR, 2.0; 95% CI, 1.940-1.947; P<0.0001); HSIL, (OR, 36.3; 95% CI, 9.5-139.5; P<0.0001); and LSIL (OR, 50.1; 95% CI, 12.0-209.0; P<0.0001). Conclusion: altogether, pre-cervical cancer in Kenyan women is characterized by koilocytosis and ASCUS probably from the high rates of HPV 16/18 infections. Promoting cancer education and screening for high risk HPV infections and pre-cancerous lesions will improve women's reproductive health.


Assuntos
Colo do Útero/patologia , Programas de Rastreamento/métodos , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Escolaridade , Feminino , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Quênia , Pessoa de Meia-Idade , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Inquéritos e Questionários , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/métodos , Adulto Jovem
5.
Pan Afr Med J ; 33: 130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558929

RESUMO

Introduction: Cancer is a public health problem that affect women more than men. The aim of the study was to describe the epidemiological and histopathological features of gynecological malignancies in the city of Yaoundé, Cameroon. Methods: This was a descriptive cross-sectional study of histologically proven gynecological cancers over a 10-year period (2008-2017) in the Gynecology and Pathological Anatomy Departments of the University Teaching Hospital of Yaoundé. Results: A total of 682 cancers were identified among which, 342 gynecological cancers, for an overall frequency of 50.1% and an annual frequency of 34.2 cases on average. There was a trend suggesting an increase annual frequency over time. The cervix was the most frequent location with 182 cases (53.2%); followed by breast with 96 cases (28.1%); endometrium with 33 cases (9.7%) and ovaries 15 cases (4.4%). These patients were on average 51.9±13.7 years old, mostly housewives (56.8%), married (60.4%), multiparous (61.3%) and referred (62.6%). Histopathologically, cervical cancer was predominantly squamous cell carcinoma (86.8%), invasive (80.9%) and well differentiated (45.5%). For breast cancers, the majority were ductal carcinomas (78.1%), invasive (92%), and histological grade SBR II (50.6%). The most common histopathological types of endometrial and ovarian cancer were adenocarcinoma (72.2%) and serous cystadenocarcinoma (46.7%), respectively. Conclusion: Gynecological cancers are common. Screening is expected to increase at 30 years for cervical cancer and start at age 40 with mammography for breast cancer.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias dos Genitais Femininos/epidemiologia , Programas de Rastreamento/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Camarões/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Estudos Transversais , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Hospitais Universitários , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
6.
BMC Womens Health ; 19(1): 112, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477083

RESUMO

BACKGROUND: Internationally, women with cervical intraepithelial neoplasia (CIN) lack knowledge about their disease, which limits their ability to take responsibility for self-care and creates negative psychosocial effects, including marital problems. Normally, screening is performed in primary care, and in case of abnormal results, the patient is referred to specialized care for follow-up and treatment. Given the lack of international literature regarding patients' experiences in primary and specialized healthcare, our study aims to: (a) investigate how women with CIN perceive the communication and management of information by healthcare providers at different moments of their healthcare and (b) identify these women's informational needs. METHODS: A qualitative exploratory study was carried out in a gynecology unit of a public hospital of the Galician Health Care Service (Spain). Participants were selected through purposive sampling. The sample consisted of 21 women aged 21 to 52 years old with a confirmed diagnosis of CIN. Semistructured interviews were recorded and transcribed. A thematic analysis was carried out, including triangulation of researchers for analysis verification. RESULTS: Two analytical themes were identified. The first was communication gaps in the diagnosis and management of information in primary and specialized healthcare. These gaps occurred in the following moments of the healthcare process: (a) cervical cancer screening in primary care, (b) waiting time until referral to specialized care, (c) first consultation in specialized care, and (d) after consultation in specialized care. The second theme was participants' unmatched informational needs. The doubts and informational needs of women during their healthcare process related to the following subthemes: (a) HPV transmission, (b) HPV infection symptoms and consequences, and (c) CIN treatment and follow-up. CONCLUSIONS: This study shows that women who have a diagnosis of CIN experience important healthcare informational challenges when accessing primary and specialized care that have several implications for their wellbeing. The information given is limited, which makes it difficult for women to understand and participate in the decision making regarding the prevention and treatment of CIN. Service coordination among different levels of care and the availability of educational materials at any given time would improve the patients' healthcare experience.


Assuntos
Neoplasia Intraepitelial Cervical , Detecção Precoce de Câncer , Assistência ao Paciente , Navegação de Pacientes/organização & administração , Neoplasias do Colo do Útero , Adulto , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/psicologia , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/psicologia , Feminino , Humanos , Competência em Informação , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Assistência ao Paciente/métodos , Assistência ao Paciente/normas , Pesquisa Qualitativa , Espanha , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/psicologia
7.
Autops. Case Rep ; 9(3): e2019104, July-Sept. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1017386

RESUMO

Rhabdomyosarcoma (RMS) is a rare solid tumor in childhood and adolescence. The higher incidence is predominant during the first two decades of life. According to the Intergroup RMS Study Group, the embryonal RMS (ERMS), botryoidal variant, constitutes a histological subtype characterized as a "grape-like" lesion of 2.0 cm to 9.5 cm. The treatment involves chemotherapy, surgery, and/or radiotherapy. We present the case of a 14-year-old female patient diagnosed with ERMS, botryoidal variant, which originated in the uterine cervix with vaginal externalization. The initial therapeutic approach comprised an initial prolapsed mass excision followed by Wertheim­Meigs surgery due to the tumor extension. No consensual protocol to ERMS treatment is found in the medical literature; however, a combined approach seems to offer a better result. The postoperative time period was uneventful and the patient followed an adjuvant therapy with vincristine, d-actinomycin, and cyclophosphamide. A comprehensive evaluation of the therapeutic options preserving the reproductive function­unfortunately not always possible­is part of a multi-disciplined care team concerning the pediatric patients.


Assuntos
Humanos , Feminino , Adolescente , Neoplasias do Colo do Útero/patologia , Rabdomiossarcoma Embrionário/patologia , Colo do Útero/anormalidades
8.
Cytogenet Genome Res ; 158(4): 205-212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434093

RESUMO

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.


Assuntos
Inativação Gênica , Antígenos de Histocompatibilidade/genética , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Apoptose/genética , Caderinas/biossíntese , Adesão Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/genética
9.
Medicine (Baltimore) ; 98(31): e16715, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374065

RESUMO

Chromosome 8 open reading frame 4 (C8orf4) is an activator of Wnt signaling pathway, and participates in the tumorigenesis and progression of many tumors. The expression levels of C8orf4 and ß-catenin were assessed via immunohistochemical staining in 100 cervical squamous cell carcinoma (CSCC) tissues, 50 high-grade squamous intraepithelial lesions (HSILs), 50 low-grade squamous intraepithelial lesions (LSILs), and 50 normal cervical tissues. Bisulfite sequencing polymerase chain reaction analysis was used to examine the methylation status of the C8orf4 locus in CSCC and normal cervical tissues. The expression rates of C8orf4 and ß-catenin were significantly higher in CSCCs or HSILs than in LSILs or normal cervical tissues (P < .05). C8orf4 expression was positively correlated with the poor differentiation of CSCCs (P = .009), and with aberrant expression of ß-catenin in CSCCs (P = .002) and squamous intraepithelial lesions (P < .001). The methylation rate of C8orf4 in CSCCs was significantly lower than that in normal cervical tissues (P = .001). The Cancer Genome Atlas genomics data also confirmed that the mRNA expression of C8orf4 was positively associated with the copy number alteration of C8orf4 (correlation coefficient = 0.213, P < .001), and negatively correlated with the methylation level of C8orf4 (correlation coefficient = -0.408, P < .001). In conclusion, the expressions of C8orf4 and ß-catenin were synergistically increased in CSCCs and HSILs and higher than those in LSILs and normal cervical tissues. The methylation level of C8orf4 is decreased in CSCCs and is responsible for the increased expression of C8orf4.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasia Intraepitelial Cervical/genética , Proteínas de Neoplasias/biossíntese , Neoplasias do Colo do Útero/genética , beta Catenina/biossíntese , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Reação em Cadeia da Polimerase , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , Adulto Jovem , beta Catenina/genética
10.
Life Sci ; 234: 116789, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31454494

RESUMO

OBJECTIVES: The aim of this study was to uncover the underlying mechanisms of cervical cancer progression and provide potential therapeutic targets for its treatment in clinic. MATERIALS AND METHODS: Real-Time qPCR was used to determine the expression levels of Linc00483, miR-508-3p and RGS17 mRNA in cervical cancer tissues and cell lines. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay was conducted to determine cell apoptosis. Western Blot was performed to detect protein expression levels. Wound healing and Transwell assay were employed to determine cell migration and invasion respectively. Online software (TargetScan, miRDB and miR TarBase) were used to predict the regulating mechanisms of Linc00483, miR-508-3p and RGS17, which were validated by dual-luciferase reporter gene system. In vivo tumor-bearing mice models were established to validate the cellular results. RESULTS: Linc00483 aberrantly overexpressed in both cervical cancer tissues and cell lines comparing to the Control groups. Knock-down of Linc00483 inhibited cervical cancer cell proliferation, invasion as well as migration, and promoted cell apoptosis. In addition, miR-508-3p was identified as the downstream target of Linc00483, and miR-508-3p inhibitor abrogated the inhibiting effects of downregulated Linc00483 on cervical cancer cell viability. Furthermore, the expression levels of Linc00483 was positively correlated with RGS17 in the clinical samples and overexpressed Linc00483 increased RGS17 expression levels in cervical cancer cells by sponging miR-508-3p. The in vivo experiments showed that knock-down of Linc00483 inhibited cervical cancer cell tumorigenesis and lung metastasis in mice models. CONCLUSIONS: Knock-down of Linc00483 inhibited the development of cervical cancer by regulating miR-508-3p/RGS17 axis.


Assuntos
Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas RGS/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Adulto , Animais , Carcinogênese/patologia , Feminino , Células HeLa , Humanos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/patologia
12.
Cancer Radiother ; 23(6-7): 765-772, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31451358

RESUMO

Image-guided brachytherapy is crucial in the management of locally advanced cervical cancers and has benefited from advances in imaging over recent decades. The recommendations of the European Brachytherapy - European Society for Radiation Oncology (GEC-ESTRO) have resulted in harmonized practices and improved clinical outcomes in terms of efficacy and toxicity. Post-implant magnetic resonance imaging (MRI) has become the reference imaging modality to guide brachytherapy. There is an increasing interest for other multimodal imaging in these patients. The metabolic information provided by Positrons Emission Tomography/computed tomodensitometry (PET/CT) is also very promising approach to guide personalized dose escalation strategies. The prognostic values of MRI and PET scanner before brachytherapy make it possible to consider personalizing the dose delivered in brachytherapy and to propose a dose escalation to patients who really need it and to possibly consider a deescalation strategy in patients with a very good prognosis. However, further studies are needed to confirm this approach.


Assuntos
Braquiterapia/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Imagem Multimodal/métodos , Órgãos em Risco/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Radioterapia Guiada por Imagem/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Feminino , Humanos , Neoplasias do Colo do Útero/patologia
13.
Cancer Radiother ; 23(6-7): 737-744, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31455591

RESUMO

The treatment of cervical cancer patients relies on surgery and radiotherapy (according to the stage) and requires a multimodal discussion before any treatment to avoid adding the morbidities of each individual intervention and to optimize functional and oncological outcomes. The places of surgery and radiotherapy have been highlighted in recent international guidelines. For early stage tumors, an exclusive surgery with or without fertility sparing (according to well defined criteria) is the therapeutic standard. For tumors with risk factors (measuring more than 2cm in size and/or presence of lymphovascular invasion) a preoperative brachytherapy can be proposed to minimize the need for postoperative external beam radiotherapy and optimize local control. For locally advanced disease, the standard treatment relies on chemoradiation followed by a brachytherapy boost. A primary paraaortic lymph node dissection may guide radiotherapy volumes and is useful to identify patients requiring a para-aortic radiotherapy. The technical evolutions of surgical approaches and technological improvement of radiotherapy and brachytherapy should be analyzed in the context of prospective studies. We review the literature on the respective places of radiotherapy and surgery for the treatment of cervical cancer.


Assuntos
Preservação da Fertilidade/métodos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Braquiterapia , Terapia Combinada/métodos , Feminino , Humanos , Metástase Linfática , Recidiva Local de Neoplasia/cirurgia , Guias de Prática Clínica como Assunto , Carga Tumoral , Neoplasias do Colo do Útero/patologia
14.
Zhonghua Fu Chan Ke Za Zhi ; 54(8): 534-540, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31461810

RESUMO

Objective: To analyze clinical outcome of high grade squamous intraepithelial lesion (HSIL) within 24 months after loop electrosurgical excision procedure (LEEP), and to explore risk factors of recurrent cervical HSIL, the risk of progress into cervical cancer and methods of follow-up. Methods: This retrospective study was carried out on 1 005 patients who underwent LEEP, diagnosing with HSIL after LEEP from January 2011 to December 2013 at Obstetrics and Gynecology Hospital Affiliated to Fudan University to confer the difference between non-recurrent group and recurrent group 24 months after the LEEP conization. Patients were followed with ThinPrep cytologic test (TCT), high risk HPV (HR-HPV) test, colposcopy guided biopsy. Results: A total of 1 005 cases were enrolled in this study with HSIL in the LEEP specimen, no residual HSIL in the 6-month follow up, and have follow up records in 24 months after LEEP. HSIL recurred in 5 cases, microinvasive carcinoma in 1 case, low grade squamous intraepithelial lesion (LSIL) in 17 cases at 12 months follow-up. HSIL recurred in 8 cases, LSIL in 11 cases, adenocarcinoma in situ in 1 case, and invasive cervical carcinoma in 1 case in Ⅰb1 stage at 24 months after LEEP. The recurrence rate was 1.3% (13/1 005) , and the progression rate was 0.3% (3/1 005) . There was no significant difference in age, length, circumference and width of LEEP between recurrent and non-recurrent patients (P>0.05) . The recurrence rate was highest in the endocervical positive margin group with 3/16, which was higher than ectocervical positive margin and negative margin (P<0.01, P=0.040, respectively). The recurrence rate of endocervical positive margin group and fibrous interstitial positive margin group showed no significant difference (P=0.320) . There was no significant difference between ectocervical positive margin and negative margin [2.8% (2/72) vs 0.7% (6/882), P=0.117]. Postoperative cytological examination combined with HR-HPV detection has a high sensitive and high negative predictor value of HSIL recurrence with both 100.0%. Multivariate logistic regression analysis showed that positive endocervical positive margin, abnormal follow-up cytological examination and positive HR-HPV after LEEP were independent factors affecting recurrence of HSIL patients after LEEP (P<0.05). Conclusions: Age, length, circumference and width of LEEP have no effect on recurrence within 24 months after HSIL. The high risk factors for HSIL recurrence within 24 months after LEEP in HSIL patients include: positive HPV, abnormal cytology, and positive endocervical positive margin. Colposcopy biopsy and endocervical curettage have important role in diagnosing HSIL recurrence and progression.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Eletrocirurgia/métodos , Lesões Intraepiteliais Escamosas Cervicais/cirurgia , Neoplasias do Colo do Útero/cirurgia , Biópsia , Neoplasia Intraepitelial Cervical/patologia , Colposcopia , Feminino , Humanos , Recidiva Local de Neoplasia , Gravidez , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia
15.
Pan Afr Med J ; 33: 38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384353

RESUMO

Introduction: Cervical cancer is a malignant proliferation of the cells of the uterine cervix and can be treated if diagnosed earlier. It is the second most common gynecological malignancy worldwide and the leading cause of cancer associated mortality among women in Africa and Cameroon. This study sort to determine the current state of knowledge of cervical cancer and its risk factors in the Buea Health District of the South West Region of Cameroon. Methods: This was a cross-sectional community based survey. We recruited 433 eligible women, in four (4) Health Areas (Molyko, Bolifamba, Muea and Buea Town) of the Buea Health District and used validated and pre-tested questionnaires to collect data. Collected data were keyed into Epi info version 7.2 statistical software and exported to SPSS Version 25 for analysis. Level of significance was set at P-value < 0.05. Results: Fifty eight percent (58%) of the participants had good knowledge of cervical cancer. 58.99% (95%CI = 54.30-63.52) had good knowledge on the risk factors of cervical cancer. 40% knew at least one of the following risk factors; cigarette smoking, many sexual partners, family history of cervical cancer, being HIV/AIDS positive and giving birth 5 or more times. There was a significant association, OR = 7.5; 95%CI = 2.14-26.33; P = 0.001; X2 = 11.4 between having heard of cervical cancer and having "good" knowledge of cervical cancer among women in Buea. Conclusion: Most of the women had heard of cervical cancer but the knowledge of the risk factors of cervical cancer among women aged 18-68 years in the Buea Health District is low. We found no association between awareness and knowledge of risk factors among the women.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias do Colo do Útero/etiologia , Adolescente , Adulto , Idoso , Camarões , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Neoplasias do Colo do Útero/patologia , Adulto Jovem
16.
Int J Nanomedicine ; 14: 5257-5270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409988

RESUMO

Background: In recent years, green synthesized silver nanoparticles have been increasingly investigated for their anti-cancer potential. In the present study, we aimed at the biosynthesis of silver nanoparticles (AgNPs) using a curcumin derivative, ST06. Although, the individual efficacies of silver nanoparticles or curcumin derivatives have been studied previously, the synergistic cytotoxic effects of curcumin derivative and silver nanoparticles in a single nanoparticulate formulation have not been studied earlier specifically on animal models. This makes this study novel compared to the earlier synthesized curcumin derivative or silver nanoparticles studies. The aim of the study was to synthesize ST06 coated silver nanoparticles (ST06-AgNPs) using ST06 as both reducing and coating agent. Methods: The synthesized nanoparticles AgNPs and ST06-AgNPs were characterised for the particle size distribution, morphology, optical properties and surface charge by using UV-visible spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Elemental composition and structural properties were studied by energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction spectroscopy (XRD). The presence of ST06 as capping agent was demonstrated by Fourier transform infrared spectroscopy (FTIR). Results: The synthesized nanoparticles (ST06-AgNPs) were spherical and had a size distribution in the range of 50-100 nm. UV-Vis spectroscopy displayed a specific silver plasmon peak at 410 nm. The in vitro cytotoxicity effects of ST06 and ST06-AgNPs, as assessed by MTT assay, showed significant growth inhibition of human cervical cancer cell line (HeLa). In addition, studies carried out in EAC tumor-induced mouse model (Ehrlich Ascites carcinoma) using ST06-AgNPs, revealed that treatment of the animals with these nanoparticles resulted in a significant reduction in the tumor growth, compared to the control group animals. Conclusion: In conclusion, green synthesized ST06-AgNPs exhibited superior anti-tumor efficacy than the free ST06 or AgNPs with no acute toxicity under both in vitro and in vivo conditions. The tumor suppression is associated with the intrinsic apoptotic pathway. Together, the results of this study suggest that ST06-AgNPs could be considered as a potential option for the treatment of solid tumors.


Assuntos
Carcinoma de Ehrlich/patologia , Curcumina/farmacologia , Química Verde/métodos , Nanopartículas Metálicas/química , Prata/farmacologia , Neoplasias do Colo do Útero/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Células HeLa , Humanos , Camundongos , Tamanho da Partícula , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual/efeitos dos fármacos , Difração de Raios X
17.
Oncol Rep ; 42(4): 1451-1458, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364732

RESUMO

Epithelial­mesenchymal transition (EMT) is closely related to tumor metastasis, and offers insight into novel strategies for cancer treatment. HMQ­T­F2 (F2) is a taspine derivative, which has excellent anticancer activity in human cervical cancer. The present study aimed to evaluate the effect of F2 on in vitro migration of HeLa cells. The present data demonstrated that F2 inhibited migration of HeLa cells by negatively regulating the Wnt signaling pathway and reversing EMT. F2 not only mediated Frizzled8, p­LRP6 and LRP6 expression, but also downregulated the phosphorylation of GSK3ß, and concurrently decreased the nucleus protein expression of MMP2, MMP3, MMP7, MMP9, and c­Myc. In addition, the expression of N­cadherin, vimentin, Snail and HIF­1α were downregulated and that of E­cadherin was upregulated after F2 treatment. F2 was also associated with the downregulation of the PI3K/Akt/mTOR signaling pathways. Notably, F2 induced HeLa cell accumulation at the S phase and cell apoptosis. These results provide evidence that F2 inhibits HeLa cell migration, proliferation and promotes apoptosis. It also reverses EMT, potentially via the PI3K/Akt signaling pathway. Therefore, F2 may be a potential therapeutic reagent against cervical cancer.


Assuntos
Alcaloides/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Alcaloides/química , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Fase S/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
18.
Zhonghua Fu Chan Ke Za Zhi ; 54(7): 458-463, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31365958

RESUMO

Objective: To explore the relationship between cervical lesions and high risk HPV (HR-HPV) viral load reflected by the cycle threshold (Ct) values of Cobas 4800 HPV (Cobas 4800) system. Methods: From August 2016 to September 2017, 7 000 women from Shenzhen, were recruited for cervical cancer screening with Cobas 4800 system and cytology co-test. Colposcope biopsies were performed on women who were positive of HPV 16, 18, and positive of HPV types other than 16,18 with cytology [≥ atypical squamous cell of undetermined signification (ASCUS)], or HPV negative but abnormal of cytology [≥ low grade squamous intraepithelial lesion (LSIL)]. The Ct values of HPV 16, 18 and all combined other types coming from Cobas 4800 system were used as an indicator of viral load to analyze the relationship between type-specific HPV load and the cervical lesions. Results: (1) Among the 7 000 screening women, 370 cases were positive for cervical cancer screening, 325 of them underwent colposcope biopsies, and coloposcopy referred rate was 87.8% (325/370). Among 325 women undergoing cervical biopsy, pathological diagnosis was 119 cases of normal cervical cervix, 151 cases of LSIL, and 55 cases of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL(+); including 53 cases of HSIL, 1 case of cervical adenocarcinoma, and 1 case of cervical squamous cell carcinoma). (2) The Ct value of HPV 16 was inversely correlated with the upgrading of the lesions (r=-0.617, P=0.000), and significant different among normal cervix,LSIL and HSIL(+) (35.4±4.5 vs 31.0±6.0 vs 26.5±4.0; F=25.537, P=0.000). There was no correlation between Ct value of HPV 18 and cervical lesions (r=-0.021, P=0.902). The Ct value of other 12 HPV types was statistically difference among normal normal cervix, HSIL(+) and cervicitis (33.0±5.3 vs 29.9±7.2 vs 29.8±5.8; F=5.087, P=0.007). Among them, LSIL and HSIL(+) were significantly lower than normal cervix (P<0.05), but there was no significant difference between LSIL and HSIL(+) (P>0.05). Conclusion: The Ct value of HPV 16 detecting in Cobas 4800 system as an indicator of virus load obviously correlates with different grades of cervical lesions, therefore could be a reference of cervical lesion existence and an indicator of lesion prognosis.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Testes de DNA para Papilomavírus Humano/instrumentação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Detecção Precoce de Câncer , Feminino , Testes de DNA para Papilomavírus Humano/métodos , Humanos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Carga Viral
19.
DNA Cell Biol ; 38(10): 1143-1146, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31464522

RESUMO

Cervical carcinoma is associated with high-risk human papillomavirus (HPV) DNA integration and usually occurs after age 21 (peak 45 years), as reflected in screening guidelines. Between 1999 and 2008, cervical carcinoma rate in adolescents aged 15-19 years was 0.15 per 100,000. HPV-negative cervical carcinoma is rare in adolescents. The youngest previously reported case was 15 years old. Treatment options for cervical carcinoma are limited after first-line therapy. Immune checkpoint inhibitors blocking programmed death receptor (PD-1) and its ligand, PD-L1, have shown objective clinical responses and are tolerable in adults with gynecologic cancers. This class of agents is well tolerated in pediatric patients. PD-1/PD-L1 is commonly expressed in gynecologic cancers but its expression may not predict clinical response. We describe an exceptional response to single agent nivolumab postradiation therapy in a 13-year-old adolescent with poorly differentiated cervical carcinoma and widespread metastatic disease.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Nivolumabe/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adolescente , Carboplatina/uso terapêutico , Carcinoma/secundário , Carcinoma/cirurgia , Feminino , Raios gama/uso terapêutico , Humanos , Histerectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Ovariectomia , Paclitaxel/uso terapêutico , Papillomaviridae , Salpingectomia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
20.
Life Sci ; 233: 116708, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369759

RESUMO

AIMS: Cervical cancer seriously affects women's health. The function of methylated alterations in the long non-coding RNAs (lncRNAs) promote the progression and metastasis of cancer. Our study aims to identify the functional effects of lncRNA methylation in cervical carcinogenesis. MAIN METHODS: Genome-wide DNA methylation of 6 samples was assessed using the Illumina Infinium MethylationEPIC BeadChip. RNA sequencing (RNA-seq) data and survival follow-up time of 307 samples from The Cancer Genome Atlas (TCGA) dataset were enrolled in this study. The statistical analysis and graphical work were mainly realized by R language. KEY FINDINGS: Methylation map identified 3962 hypermethylated CpG sites and 4484 hypomethylated CpG sites in cervical cancer (|Δß| ≥ 0.20). Bioinformatic analysis of the lncRNA expression identified 363 upregulated and 664 downregulated lncRNAs with log2 (fold change) ≥ 1.00 in squamous cervical carcinoma (SCC) samples. Weighted gene co-expression network analysis (WGCNA) and Venn diagram revealed that lncRNA MAGI2 antisense RNA 3 (lncRNA MAGI2-AS3), lncRNA WT1 antisense RNA (lncRNA WT1-AS) and lncRNA SOX21 antisense divergent transcript 1 (lncRNA SOX21-AS1) were important methylation changed lncRNAs. Kaplan-Meier survival curves showed only lncRNA SOX21-AS1 had clinical prognostic value in cervical cancer. Gene set enrichment analysis (GSEA) suggest that lncRNA SOX21-AS1 involve in the multiple cellular processes and might significantly suppress cervical tumorigenesis. SIGNIFICANCE: These insights into the functional role of lncRNA SOX21-AS1 DNA methylome alterations in cervical cancer might promote clinically new applicable in diagnosis and prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/patologia , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Proliferação de Células , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/genética
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