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1.
Lancet Oncol ; 24(6): 701-708, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37269846

RESUMO

BACKGROUND: Small cell carcinoma of the cervix is a rare but poor prognosis pathological type of cervical cancer, for which advice in clinical guidelines is unspecific. We therefore aimed to investigate the factors and treatment methods that affect the prognosis of patients with small cell carcinoma of the cervix. METHODS: In this retrospective study, we collected data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries cohort and a Chinese multi-institutional registry. The SEER cohort included females diagnosed with small cell carcinoma of the cervix between Jan 1, 2000, and Dec 31, 2018, whereas the Chinese cohort included women diagnosed between Jun 1, 2006, and April 30, 2022. In both cohorts, eligibility was limited to female patients older than 20 years with a confirmed diagnosis of small cell carcinoma of the cervix. Participants who were lost to follow-up or those for whom small cell carcinoma of the cervix was not the primary malignant tumour were excluded from the multi-institutional registry, and those with an unknown surgery status (in addition to those for whom small cell carcinoma of the cervix was not the primary malignant tumour) were excluded from the SEER data. The primary outcome of this study was overall survival (length of time from the date of first diagnosis until the date of death from any cause, or the last follow-up). Kaplan-Meier analysis, propensity score matching, and Cox-regression analyses were used to assess treatment outcomes and risk factors. FINDINGS: 1288 participants were included in the study; 610 in the SEER cohort and 678 in the Chinese cohort. Both univariable and multivariable Cox regression analysis (SEER hazard ratio [HR] 0·65 [95% CI 0·48-0·88], p=0·0058; China HR 0·53 [0·37-0·76], p=0·0005) showed that surgery was associated with a better prognosis. In subgroup analyses, surgery remained a protective factor for patients with locally advanced disease in both cohorts (SEER HR 0·61 [95% CI 0·39-0·94], p=0·024; China HR 0·59 [0·37-0·95]; p=0·029). Furthermore, the protective effect of surgery was observed among patients with locally advanced disease after propensity score matching in the SEER cohort (HR 0·52 [95% CI 0·32-0·84]; p=0·0077). In the China registry, surgery was associated with better outcomes in patients with stage IB3-IIA2 cancer (HR 0·17 [95% CI 0·05-0·50]; p=0·0015). INTERPRETATION: This study provides evidence that surgery improves outcomes of patients with small cell carcinoma of the cervix. Although guidelines recommend non-surgical methods as first-line treatment, patients with locally advanced disease or stage IB3-IIA2 cancer might benefit from surgery. FUNDING: The National Key R&D Program of China and the National Natural Science Foundation of China.


Assuntos
Carcinoma de Células Pequenas , Neoplasias do Colo do Útero , Feminino , Humanos , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/patologia , População do Leste Asiático , Estadiamento de Neoplasias , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Programa de SEER , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
2.
Br J Cancer ; 128(11): 2054-2062, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36997661

RESUMO

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular determinants. METHODS: Whole-genome sequencing on 23 pathologically confirmed patients was employed to depict the genomic profile of primary OCCCs. APOBEC3B expression and digital pathology-based Immunoscore were assessed by performing immunohistochemistry and correlated with clinical outcomes. RESULTS: An APOBEC-positive (APOBEC+) subtype was identified based on the characteristic mutational signature and prevalent kataegis events. APOBEC + OCCC displayed favourable prognosis across one internal and two external patient cohorts. The improved outcome was ascribable to increased lymphocytic infiltration. Similar phenomena of APOBEC3B expression and T-cell accumulation were observed in endometriotic tissues, suggesting that APOBEC-induced mutagenesis and immunogenicity could occur early during OCCC pathogenesis. Corroborating these results, a case report was presented for an APOBEC + patient demonstrating inflamed tumour microenvironment and clinical response to immune checkpoint blockade. CONCLUSIONS: Our findings implicate APOBEC3B as a novel mechanism of OCCC stratification with prognostic value and as a potential predictive biomarker that may inform immunotherapeutic opportunities.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/genética , Prognóstico , Mutação , Linfócitos T/patologia , Adenocarcinoma de Células Claras/genética , Microambiente Tumoral , Citidina Desaminase , Antígenos de Histocompatibilidade Menor
3.
BMC Cancer ; 23(1): 608, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37391693

RESUMO

PURPOSE: To assess the clinical characteristics and the risk factors related to the unfavorable prognosis of endometrioid ovarian carcinoma (EOVC) based on data from the Surveillance, Epidemiology, and End Results (SEER) database and two clinical centers in China. METHODS: Data were extracted from the SEER database and two clinical centers in China (2010 ~ 2021), 884 cases and 87 patients with EOVC were selected, respectively. Overall survival (OS) and progression-free survival (PFS) were compared among the different groups using Kaplan-Meier analysis. The Cox proportional-hazards model was used to identify independent prognostic factors related to EOVC. A nomogram was constructed based on the risk factors of the SEER database affecting prognosis and the discrimination and calibration of the nomogram were evaluated by C-index and calibration curves. RESULTS: The average age at diagnosis of patients with EOVC in the SEER database and two centers in China was 55.77 ± 12.40 years and 47.14 ± 11.50 years, 84.7% and 66.6% of them were diagnosed at FIGO stage I ~ II, respectively. In the SEER database, age over 70 years, advanced FIGO stage, tumor grade 3, only unilateral salpingo-oophorectomy were independent risk factors of unfavorable prognosis. In two clinical centers in China, 27.6% of EOVC patients were diagnosed with synchronous endometriosis. Advanced FIGO stage, HE4 > 179 pmol/L and bilateral ovarian involvement significantly correlated with poor OS and PFS in Kaplan-Meier analysis. Body mass index (BMI) < 19.34 kg/m2 was an independent risk factor relating to OS and PFS. Additionally, C-index of internal and external verification for the nomogram were 0.812 and 0.754 respectively, revealing good accuracy and clinical applicability. CONCLUSIONS: Most patients were diagnosed at early stage, low grade and had better prognosis. Asian/Pacific Islander and Chinese diagnosed with EOVC were more likely to be younger than whites and blacks. Age, tumor grade and FIGO stage (SEER database) and BMI (two centers) are independent prognostic factors. HE4 appears to be more valuable in prognostic assessment compared with CA125. The nomogram had good discrimination and calibration for predicting prognosis, providing a convenient and reliable tool for clinical decision-making for patients with EOVC.


Assuntos
Carcinoma Endometrioide , Neoplasias Ovarianas , Feminino , Humanos , Idoso , Prognóstico , Nomogramas , Carcinoma Epitelial do Ovário , China/epidemiologia , Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/terapia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/terapia
4.
Gynecol Oncol ; 167(3): 502-512, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36270832

RESUMO

BACKGROUND: Patients with epithelial ovarian cancer (EOC) can benefit from poly- (ADP ribose) polymerase inhibitors (PARPi) therapy. However, PARPi resistance has become a challenge in clinical practice, and its mechanism requires further exploration. METHODS: We established three PARPi-resistant cell strains following olaparib exposure. CCK-8, clonogenic survival, transwell, wound healing, cell cycle, RT-qPCR and western blot assays were performed to explore the functional phenotype of the resistant cells. Whole-exome sequencing and RNA-sequencing were performed to identify the altered genes. Stable knockdown and overexpression were used to investigate the role of EP300, an upstream regulator of E-cadherin and epithelial-mesenchymal transition (EMT), in cell lines. We further validated the finding in clinical ovarian cancer samples by immunohistochemistry. RESULTS: We combined public datasets to obtain an integrated PARPi sensitivity profile in EOC cells, which indicated that primary PARPi resistance could not be fully explained by mutations in BRCA1/2 or homologous recombination deficiency related genes. Genomic and transcriptome analyses revealed distinct mechanisms between primary and acquired resistance. Long-term PARPi treatment induced accumulation of de novo single nucleotide variants (SNV), and the complete frame-shift deletion of PARP1 was detected in the A2780 resistant strain. Additionally, the depressed histone acetyltransferase of EP300 could cause resistant phenotype through activated EMT process in vitro, and associated with PARPi-resistance in EOC patients. CONCLUSION: Long-term PARPi treatment led to evolutionary genomic and transcriptional alterations that were associated with acquired resistance, among which depressed EP300 partly contributed to the resistant phenotype.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética
5.
J Minim Invasive Gynecol ; 29(5): 673-682, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35051658

RESUMO

STUDY OBJECTIVES: The purpose of this study was to evaluate the feasibility of "cuff-sleeve" sutures for reconstructing a functional neocervix in laparoscopic radical trachelectomy (RT). DESIGN: A retrospective analysis of a case series. SETTING: A teaching hospital. PATIENTS: Twenty-five patients who were diagnosed as early-stage cervical cancer from June 2017 to October 2020 in Sun Yat-sen Memorial Hospital. INTERVENTIONS: Laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients successfully underwent the laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction, and no intraoperative complications occurred or conversion to laparotomy was needed. For all patients, approximately 80% of the cervical length was removed. Surgical radicality and negative surgical margins were also confirmed. During a median follow-up time of 29 months (range 8-48 months), no severe postoperative complications were observed. No cervical stenosis or secondary abnormal menstruation was reported. After the removal of the uterine stent 6 months after surgery, the neocervix length was approximately 14 mm (range 10-19 mm) and almost all the neocervixes were restored closely to the original anatomy. Four of 8 patients attempting actively to conceive were successful, and the cervical length of these pregnant patients was greater than or equal to 15 mm in all but one measurement at different gestational age. Three patients were ongoing pregnant, and the other had delivered successfully with a 16- mm cervix at term without cerclage. CONCLUSION: The "cuff-sleeve" suture method in cervicovaginal reconstruction is feasible in laparoscopic RT. This simplified suture technique can provide a functional neocervix to reduce cervical stenosis and incompetence.


Assuntos
Laparoscopia , Traquelectomia , Neoplasias do Colo do Útero , Constrição Patológica/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Gravidez , Estudos Retrospectivos , Técnicas de Sutura , Suturas , Traquelectomia/métodos , Neoplasias do Colo do Útero/cirurgia
6.
J Obstet Gynaecol Res ; 48(7): 1867-1875, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35537684

RESUMO

AIM: The purpose of this study was to investigate the surgical techniques and clinical feasibility of nonuterine manipulator and enclosed colpotomy to avoid cancer cell spillages in laparoscopic radical trachelectomy (LRT) for patients with early-stage cervical cancer. METHODS: We performed the newly optimized surgical techniques of round ligament suspension and vaginal purse-string suture in LRT in 12 patients with early-stage cervical cancer from May 2019 to October 2020. Surgical information and postoperative results were recorded. RESULTS: All 12 patients successfully underwent LRT with round ligament suspension and vaginal purse-string suture, and no conversion to laparotomy was required. The median operation time was 268.5 min (range 200-320 min), including 5 min of round ligament suspension, and the median blood loss was 20 mL (range 5-50 mL). The median number of pelvic lymph nodes removed was 27 (range 19-35), and median amounts of paracervical tissue was 24 mm (range 21-26 mm) and vaginal tissue was 18 mm (range 16-26 mm). No intraoperative complication or serious postoperative complications were reported. CONCLUSION: Round ligament suspension and vaginal purse-string suture techniques are feasible and effective in LRT. They can replace uterine manipulator and unprotected colpotomy with satisfactory perioperative outcomes.


Assuntos
Laparoscopia , Ligamentos Redondos , Traquelectomia , Neoplasias do Colo do Útero , Feminino , Humanos , Laparoscopia/métodos , Ligamentos Redondos/patologia , Técnicas de Sutura , Suturas , Traquelectomia/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
7.
Br J Cancer ; 124(2): 414-424, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33087896

RESUMO

BACKGROUND: We aimed to comprehensively evaluate the immunologic landscape at baseline and upon chemotherapy in cervical cancer. The information should aid ongoing clinical investigations of checkpoint blockade immunotherapies in this disease setting. METHODS: A series of 109 cervical carcinoma patients was retrospectively assayed before and after neoadjuvant chemotherapy. Tumour-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, PD-L1) were assessed by immunohistochemistry. RNA sequencing analysis was performed on matched pre- and post-treatment fresh-frozen tissues. RESULTS: At diagnosis, diverse immune cell types including CD20+ B cells, CD3+ T cells, CD56+ natural killer (NK) cells, and CD68+ macrophages were detected in different proportions of cervical carcinoma. Unsupervised hierarchical clustering evidently showed that CD4+ and CD8+ T cell abundance correlated with PD-L1 expression. Based on the immune infiltration patterns, the patients could be stratified into four groups with prognostic relevance, namely, 'immuno-active', 'immuno-medial', 'immuno-NK', and 'immuno-deficient'. Neoadjuvant chemotherapy was associated with increased CD4, CD8, CD20, and CD56 signals, most prominently in good responders. Transcriptomic data corroborated the improved anticancer immunity and identified immunosuppressive CD200 upregulation following chemotherapeutic intervention. CONCLUSIONS: A subset of cervical cancer harbours active immune microenvironment, and chemotherapy treatment may further exert locoregional immunostimulation. Immune checkpoint inhibitors as combination or maintenance therapies warrant future exploration in clinic.


Assuntos
Antineoplásicos/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/tratamento farmacológico , Carcinoma/imunologia , Carcinoma/patologia , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Feminino , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Microambiente Tumoral/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia
8.
Cancer Cell Int ; 21(1): 252, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962626

RESUMO

PURPOSE: The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined. METHODS: We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored. RESULTS: Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025-0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells. CONCLUSION: HHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.

9.
Med Sci Monit ; 26: e928826, 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33361739

RESUMO

BACKGROUND The utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis. MATERIAL AND METHODS A retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002-2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated. RESULTS A total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml. CONCLUSIONS The incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.


Assuntos
Antígeno Ca-125/metabolismo , Neoplasias do Endométrio/patologia , Neoplasias Ovarianas/secundário , Receptores de Estrogênio/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Fatores de Risco
10.
Gynecol Oncol ; 151(3): 533-541, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30336948

RESUMO

OBJECTIVE: Resistance to radiotherapy accounts for most treatment failures in cervical cancer patients who receive radical radiation therapy. To discover the possible mechanism of radioresistance and improve the 5-year survival rate, we focused on how sex-determining region Y-box 2 (SOX2) mediates radioresistance in cervical cancer as well as on the interaction between SOX2 and the hedgehog (Hh) signaling pathway in this study. METHODS: We established the acquired radioresistant subclone cells Hela-RR and Siha-RR. RT-qPCR, Western blot analysis, IHC, clonogenic survival assay, CCK-8 assay, apoptosis analysis, cell cycle analysis and xenograft models were used to explore the relationship between SOX2 expression and radiation resistance and to determine how SOX2 mediates radioresistance in cervical cancer. Furthermore, luciferase reporter and ChIP-PCR assays were utilized to assess the interaction between SOX2 and the Hh signaling pathway. RESULTS: Our research suggested that high expression of SOX2 was responsible for radioresistance in cervical cancer. SOX2 was observed to be closely related to irradiation-induced survival, proliferation, apoptosis, and cell cycle changes. The Hh signaling pathway was found to be activated in Hela-RR and Siha-RR, and the activation changed with SOX2 expression. IHC staining of SOX2 and Gli1 showed a close relationship between SOX2 and the Hh pathway. Luciferase reporter and ChIP-PCR assays demonstrated that SOX2 interacted with the Hh signaling pathway by occupying the HHAT promoter. CONCLUSIONS: SOX2 is a potential therapeutic target of irradiation resistance in cervical cancer. It mediates radioresistance in cervical cancer via the Hh signaling pathway.


Assuntos
Proteínas Hedgehog/genética , Fatores de Transcrição SOXB1/genética , Neoplasias do Colo do Útero/genética , Animais , Feminino , Proteínas Hedgehog/metabolismo , Humanos , Camundongos Nus , Pessoa de Meia-Idade , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais , Neoplasias do Colo do Útero/metabolismo
11.
Med Sci Monit ; 24: 3042-3049, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29742071

RESUMO

BACKGROUND The aim of this study was to evaluate the safety and efficacy of a 'baseball' suture technique for uterine myomectomy incision closure in laparoscopic surgical enucleation of uterine leiomyoma (fibroid). MATERIAL AND METHODS The study included 20 patients who underwent laparoscopic myomectomy with a 'baseball' suture technique, compared with 20 patients who underwent laparoscopic myomectomy with a standard suture method. Clinical characteristics, perioperative and follow-up data were compared between the two groups. RESULTS For the study group, compared with the standard or control group, had a significantly reduced operation time (60.15±9.97 min vs. 71.85±9.74 min) and suturing time (18.05±4.71 min vs. 28.35±3.13 min) (both p<0.05), significantly less intraoperative blood loss (93.25±19.62 ml vs. 121.50±24.87 ml) (p<0.05) and significantly less reduction in postoperative hemoglobin levels (8.9±1.97 g/L vs. 11.15±2.23 g/L) (p<0.05). There were no statistically significant differences between the two groups in duration of the use of the indwelling drainage tube, drainage volume, or time to recovery of gastrointestinal function (all, p>0.05). Following surgery, blood transfusion was given to one patient in the study group and two patients in the control group. One patient from each group had a fever. There was no significant difference in pregnancy outcomes between the two groups. CONCLUSIONS The 'baseball' suture technique for closure of the uterine incision is a safe and effective method for use in laparoscopic myomectomy. However, the long-term recovery outcomes require further study.


Assuntos
Laparoscopia , Leiomioma/cirurgia , Técnicas de Sutura , Miomectomia Uterina , Neoplasias Uterinas/cirurgia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Gravidez , Resultado da Gravidez , Técnicas de Sutura/efeitos adversos , Miomectomia Uterina/efeitos adversos
12.
Med Sci Monit ; 24: 7952-7957, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30398217

RESUMO

BACKGROUND The aim of this study was to compare magnetic resonance imaging (MRI) and hysteroscopy (HS) for assessing cervical involvement in early-stage endometrial adenocarcinoma in order to establish a more reliable screening method to aid in clinical decision-making. MATERIAL AND METHODS A retrospective analysis was performed on the clinicopathological data from 88 patients with stage I or II endometrial adenocarcinoma who underwent MRI and HS prior to surgery in the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Chi-square and Fisher's exact tests were performed to compare the accuracy, sensitivity, specificity, and positive and negative predictive values in the diagnosis of cervical involvement by MRI and HS. The relationship between clinicopathological factors and the deviation of diagnosis by MRI and HS from that by pathology was also analyzed. RESULTS The accuracy of assessing cervical conditions was 93.2% by MRI and 55.7% by HS. Among these variables, the accuracy, specificity, and positive predictive values of MRI were significantly different from those of HS, while the sensitivity and negative predictive values of MRI and HS were not significantly different from each other. Age, tumor size, tumor differentiation, and depth of myometrial invasion were not associated with the differences in cervical assessment between MRI and HS. However, the tumor location may affect assessment by HS. CONCLUSIONS MRI is better than HS for cervical assessment. The negative predictive values of both MRI and HS are high and unsatisfactory.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , China , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histeroscopia/métodos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Tumour Biol ; 37(8): 11469-77, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27012551

RESUMO

Galectin-3 (Gal-3) has been found to be involved in the tumor progression and chemoresistance of epithelial ovarian cancer (EOC). Some studies have shown that Gal-3 may interact with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, it is unclear whether the effects of Gal-3 on the metastasis and chemosensitivity of EOC are related to NF-κB. In this study, we aimed to explore whether Gal-3 promoted progression and carboplatin resistance in EOC via NF-κB pathway. Plasmid transfection and RNA interference were used to upregulate or downregulate the expression of Gal-3 in ovarian cancer cell lines. Then, the expression of Gal-3 and the protein expressions of phosphorylation NF-κB pathway molecules were further detected by Western blot. Transwell migration assay was employed to detect the effects of Gal-3 on the migration and invasion of ovarian cancer cell lines. After treatment with carboplatin, flow cytometry (FCM) was employed to detect the effects of Gal-3 on carboplatin-induced apoptosis. Immunofluorescence technique was used to examine the translocation of phosphorylated P65 into the nucleus in ovarian cancer cells after the upregulation of Gal-3. After the knockdown of Gal-3 by small interfering RNA (siRNA), the migration and the invasion of cancer cells were significantly inhibited while the apoptosis and the sensitivities to carboplatin increased. Western blot showed reduction in the phosphorylation components of the NF-κB pathway: inhibitor of kappa B (IκB), IκB kinase (IKK), and P65. However, after the Gal-3 upregulation by plasmid transfection, the capabilities of migration and invasion of cancer cells were significantly promoted while the apoptosis and the sensitivities to carboplatin decreased. Immunofluorescence showed increased nuclear translocation of P65. Inhibitors of the NF-κB pathway did not affect the Gal-3 expression level in ovarian cancer cells. Gal-3 may affect the migratory and invasive capabilities of cancer cells as well as the chemosensitiviy to carboplatin in EOC by acting through the NF-κB pathway.


Assuntos
Resistencia a Medicamentos Antineoplásicos/fisiologia , Galectina 3/metabolismo , NF-kappa B/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Transdução de Sinais/fisiologia , Apoptose , Proteínas Sanguíneas , Western Blotting , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Imunofluorescência , Galectinas , Humanos , Microscopia Confocal , Invasividade Neoplásica/patologia , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
14.
Med Sci Monit ; 22: 408-14, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26852916

RESUMO

BACKGROUND In cervical adenocarcinoma, surgical treatment involves bilateral oophorectomy, which affects the long-term quality of life. The aim of our study was to access the incidence of ovarian metastasis in early-stage cervical adenocarcinoma and to suggest an algorithm for the triage of these patients to preserve the ovaries. MATERIAL AND METHODS A total 101 patients with cervical adenocarcinoma who had undergone radical hysterectomy with pelvic lymphadenectomy and bilateral oophorectomy were included in this study. Data on the clinicopathologic characteristics of the cases were collected and low risk factors for ovarian metastasis in early-stage cervical adenocarcinoma were analyzed. RESULTS The ovary metastasis rate of cervical adenocarcinoma in this study was 4.95%, while it is only 2% in stage IB1. Pathological grade, LSVI, lymph node status, tumor size, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis, while LSVI, lymph node status, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis in stage IB. Multivariate analysis revealed that LVSI and lymph node metastasis were independent risk factors for ovarian metastasis in all stages of cervical adenocarcinoma, but involvement of the junction of the cervix and the body of the uterus was an independent risk factor for ovarian metastasis in stage IB. CONCLUSIONS The incidence of ovarian metastasis in cervical adenocarcinoma is low. Our study suggests that ovarian preservation is safe and feasible in patients with no risk factors for ovarian metastasis. Further prospective studies are warranted.


Assuntos
Preservação da Fertilidade/métodos , Neoplasias Ovarianas/secundário , Ovário/fisiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Algoritmos , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Ovariectomia/métodos , Ovário/cirurgia , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco
15.
Zhonghua Yi Xue Za Zhi ; 96(3): 203-6, 2016 Jan 19.
Artigo em Zh | MEDLINE | ID: mdl-26879723

RESUMO

OBJECTIVE: To investigate the rate of ovarian metastasis and its related factors in patients with cervical adenocarcinoma, and explore whether the ovary should be reserved or not in cervical adenocarcinoma. METHOD: The clinical data of 111 patients with cervical adenocarcinoma who received extensive total hysterectomy plus pelvic lymph node resection in Sun Yat-sen Memorial Hospital and Quanzhou Women's and Children's Hospital from January 2008 to December 2014 were collected and analyzed by single factor χ(2) test and multivariate logistic regression analysis. RESULTS: The median age of the included 111 cases of cervical adenocarcinoma was 44. Sixty-five of the patients were stage Ⅰb1, while 46 were stage Ⅰb2. The single factor analysis indicated that lymph-vascular space invasion(LSVI), lymph node status, interstitial infiltration depth, parametrial involvement and involvement of cervical body junction were associated with ovarian metastasis. Multivariate analysis indicated that LSVI (HR: 47.01, 95% CI: 2.48-890.03, P=0.010) and lymph node status (HR: 23.58, 95% CI: 1.20-463.21, P=0.038) were independent risk factors for ovarian metastasis. CONCLUSIONS: Ovarian metastasis rate of stage Ⅰb cervical adenocarcinoma is low; patients with age less than or equal to 45 years old, negative LSVI, <1/2 cervical stromal invasion, no lymph node metastasis and no cervical body junction involvement can consider preservation of ovary; but these findings still need to be further confirmed by large randomized controlled trials.


Assuntos
Adenocarcinoma/secundário , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Análise Multivariada , Estadiamento de Neoplasias , Pelve , Estudos Retrospectivos , Fatores de Risco
16.
Chin J Cancer ; 34(9): 413-9, 2015 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-26253113

RESUMO

BACKGROUND: Occult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP. METHODS: A total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed. RESULTS: Of the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence. CONCLUSIONS: Perioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.


Assuntos
Histerectomia , Excisão de Linfonodo , Neoplasias Primárias Desconhecidas , Complicações Pós-Operatórias , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco
17.
Gynecol Oncol Rep ; 53: 101385, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623267

RESUMO

Introduction: Epithelial Ovarian cancer most commonly presents at advanced stages with extra-abdominal disease metastasis. Notably, enlarged cardiophrenic lymph nodes are found in 10.5-62 % of patients with advanced ovarian cancer. However, the safety and feasibility of cardiophrenic lymph nodes dissection as a component of debulking surgery remains controversial (Acs et al., 2022, Agusti et al., 2024). Case/methods: We present a surgical video demonstrating the technique of bulky pericardial mass and metastatic cardiophrenic lymph nodes resection by transdiaphragmatic approach in advanced ovarian cancer. After the complete excision of intra-abdominal disease at laparotomy, the diaphragm is exposed, following the liver mobilization. According to the preoperative radiological examinations, the pericardial mass in the diaphragmatic space is reconfirmed, and then carefully removed by blunt and sharp dissection. Next, the pericardial cavity is closed by continuous suture. Through the transdiaphragmatic access to thoracic cavity, the pericardial fat pad containing cardiophrenic lymph nodes is explored and completely resected in view throughout. The diaphragm incision is closed continuously using non-absorbable suture with a biofilm, meanwhile, performing air aspiration in thoracic cavity. Conclusion: We demonstrate that advanced ovarian cancer with extra-abdominal diseases, such as bulky pericardial mass and cardiophrenic lymph nodes, should not be an absolute contraindication to a planned complete debulking surgery. Based on our growing experience, transdiaphragmatic approach is a safe and feasible access for metastatic cardiophrenic lymph nodes dissection.

18.
Eur J Surg Oncol ; 50(1): 107276, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38064863

RESUMO

INTRODUCTION: The aim of this study was to assess the safety of fertility-sparing surgery (FSS) in stage I endometrioid epithelial cancer (EEOC) and mucinous ovarian cancer (MOC). METHODS: A retrospective case‒controlled study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on stage I EEOC and MOC between 2000 and 2016. The effects of FSS on overall survival (OS) were compared using log-rank tests. Univariate and multivariate Cox analyses were performed to control for confounders. RESULTS: The study identified 970 patients with FIGO stage I EEOC and 810 with stage I MOC. Of these patients, 116 (12.0%) EEOC and 268 (33.1%) MOC patients underwent fertility-sparing surgery. The results showed that patients with G3 EEOC had a worse 5-year OS than patients with G1 EEOC (96.1% vs. 90.1%, p = 0.020). IC stage MOC patients had a worse prognosis than IA and IB stage patients (94.9% vs. 88.7%, p = 0.001). FSS did not significantly affect the 5-year OS of patients with EEOC (94.8% vs. 95.4%, p = 0.687) or MOC (95.9% vs. 92.3%, p = 0.071). Further subgroup analysis according to tumor stage and histological grade did not show a worse OS with FSS in stage I EEOC or MOC patients, even with high-risk types such as G3 histology and IC phase. In a multivariable analysis, the application of FSS was not associated with inferior OS in EEOC or MOC. CONCLUSIONS: FSS for patients with stage I EEOC or MOC does not lead to worse outcomes than radical surgery, making it a viable option for young patients with early-stage disease wishing to preserve fertility.


Assuntos
Preservação da Fertilidade , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Preservação da Fertilidade/efeitos adversos , Preservação da Fertilidade/métodos , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/patologia , Tratamentos com Preservação do Órgão/métodos , Estadiamento de Neoplasias
19.
Int J Surg ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093863

RESUMO

OBJECTIVES: To describe treatment patterns and prognoses for clear cell adenocarcinoma of the cervix (CCAC), a poorly understood rare tumor. METHODS: A retrospective case‒control study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on females diagnosed with CCAC between 2000 and 2019. Kaplan‒Meier analysis, propensity score matching, Cox regression analysis, and subgroup analysis were used to assess treatment outcomes and risk factors. RESULTS: Of the 52,153 patients with cervical cancer in the SEER database, 528 had CCAC. Overall survival (OS) was worse for patients with early-stage and locally advanced CCAC disease, although no differences in survival were observed for patients with stage IVB disease compared to those with other histologies. In our investigation into treatment patterns, we have discovered that surgical treatment was the preferred choice for the majority of patients with locally advanced CCAC (58.5%). Further, Kaplan-Meier analysis revealed that surgery improved OS in CCAC patients (65.6% vs. 25.3%, P=0.000), with similar results in locally advanced-stage patients (57.9% vs. 26.7%, P=0.000). Moreover, multivariate Cox regression analysis revealed that surgery was significantly associated with a more favorable prognosis in CCAC patients with locally advanced disease (HR 0.299, 95% CI: 0.153-0.585, P=0.000). Consistent findings were observed following propensity score matching (HR 0.283, 95% CI: 0.106-0.751, P=0.011). According to the subgroup analyses, surgical intervention continued to show a beneficial effect on CCAC patients with locally advanced disease (HR=0.31, 95% CI 0.21-0.46, P<0.001). In particular, we also found that compared to patients who received primary radiotherapy (RT), those with CCAC who underwent radical surgery exhibited a significantly prolonged OS in locally advanced CCAC patients. Furthermore, multivariate Cox regression analysis revealed that surgery was associated with better outcomes in patients with stage IB3-IIA2 and locally resectable stage IIIC patients (HR 0.207, 95% CI=0.043-0.991, P=0.049). However, this trend was not observed for patients with stage IIB-IVA (except locally resectable stage IIIC) CCAC. CONCLUSION: Surgery should be considered the preferred treatment option for patients with locally advanced CCAC at stage IB3-IIA2 and locally resectable stage IIIC.

20.
Gynecol Oncol Rep ; 54: 101432, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39021506

RESUMO

Objective: To explore the feasibility of the "cuff-sleeve" suture method in improving the uterine blood supply after radical trachelectomy (RT). Study design: Patients in the "cuff-sleeve" (n = 25) and traditional group (n = 10) underwent computed tomography angiography (CTA) to evaluate the residual uterine blood supply pattern after the surgery, and the preoperative group patients (n = 20) underwent CTA before the procedure. Results: The uteri of the 20 patients in the preoperative group were all supplied by bilateral uterine arteries of average diameter, 2.25 ± 0.35 mm. The uterine artery-supplying, hybrid supplying, and ovarian artery-supplying patterns accounted for 40 %, 36 %, and 24 % in the "cuff-sleeve" group and 20 %, 50 %, and 30 %, respectively, in the traditional group. The average diameter of the uterine arteries among the uterine artery-supplying pattern in the "cuff-sleeve" group (1.98 ± 0.36 mm) was more extensive than that in the traditional group (1.73 ± 0.15 mm) (p = 0.049). As also, the ovarian artery diameter of the hybrid supplying pattern in the "cuff-sleeve" group (1.65 ± 0.25 mm) was significantly larger than that in the traditional group (1.50 ± 0.35 mm) (p = 0.010). Additionally, while the pregnancy rate in the "cuff-sleeve" group (50.0 %) was higher than that in the traditional group (25.0 %), this difference was not statistically significant. Conclusions: The "cuff-sleeve" suture method was associated with increased diameter of the uterine and ovarian vessels and may be a feasible method to improve the uterine blood supply and pregnancy rate after radical trachelectomy. It still warrants further evaluation for both fertility and oncologic outcomes.

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