RESUMO
With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.
Assuntos
Infecções por Papillomavirus , Médicos , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Papillomavirus Humano , Detecção Precoce de Câncer/métodos , Papillomaviridae/genética , Manejo de Espécimes/métodos , Esfregaço Vaginal/métodos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Endometrial cancer (EC) and colorectal cancer (CRC) may share a common genetic background. In a subset of patients, the two malignancies can coexist either at the time of diagnosis (synchronous) or develop consequently (metachronous). The purpose of this nationwide, population-based study was to investigate the occurrence and clinical outcomes of synchronous/metachronous EC/CRC in Taiwanese women. MATERIALS AND METHODS: Data for women diagnosed with EC and/or CRC between 2007 and 2015 were retrospectively retrieved from the nationwide Taiwan Cancer Registry. Mortality data were obtained from the National Death Registry. Women with synchronous/metachronous EC/CRC versus EC or CRC were compared in terms of clinical characteristics and outcomes. RESULTS: Of the 62,764 Taiwanese women diagnosed with EC and/or CRC during the study period, 167 (0.3%) had synchronous/metachronous EC/CRC. Among them, 72 cases (43.1%) presented with EC followed by CRC, 66 (39.5%) with CRC followed by EC, and 29 (17.4%) with synchronous EC/CRC. Kaplan-Meier estimates for time-to-event data revealed that the 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC were 39.6% and 42.1%, respectively. The 5-year overall survival rates of women with metachronous EC/CRC who had an initial diagnosis of EC, CRC, and synchronous EC/CRC were 73.9%, 70.9%, and 37.0%, respectively. CONCLUSIONS: Endometrial cancer is the most common first tumor in Taiwanese women with metachronous EC/CRC. The 2-year risk rates of developing a metachronous tumor of interest (CRC or EC) in women diagnosed with an initial EC and CRC are not negligible. Surveillance for CRC is recommended for all women diagnosed with EC. The clinical outcomes of synchronous EC/CRC are markedly less favorable.
Assuntos
Neoplasias Colorretais , Neoplasias do Endométrio , Neoplasias Primárias Múltiplas , Segunda Neoplasia Primária , Neoplasias Colorretais/epidemiologia , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/patologia , Estudos RetrospectivosRESUMO
Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.
Assuntos
Alphapapillomavirus/genética , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Alphapapillomavirus/patogenicidade , Conização , Progressão da Doença , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Teste de Papanicolaou , Estudos Prospectivos , Taiwan , Resultado do Tratamento , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/virologiaRESUMO
PURPOSE: To investigate the prognostic factors and impact of adjuvant treatment on uterine carcinosarcoma (UCS). METHODS: A retrospective review of UCS patients treated between 2005 and 2019 was conducted. International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system was used. Multivariate stepwise Cox proportional hazard regression models were used to identify the independent predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 138 patients were eligible for descriptive analysis. Excluding 12 patients without surgery, 126 patients with adequate clinicopathologic data were included for prognostic analysis. The median follow-up for survivors was 51.8 months. 5-year OS and PFS rates for FIGO stage I, II, III, IV were 64.5% and 51.8%, 60.8% and 57.7%, 47.7% and 45.9%, 5.1% and 4.1%, respectively. By multivariate analysis, six models each for PFS and OS were formulated including highly correlated variables alternatively. Adjuvant chemoradiation was consistently selected as an independent prognostic factor for OS (hazard ratio [HR] 0.10-0.22, all p < 0.001) and PFS (HR 0.12-0.23, all p < 0.001), while adjuvant chemotherapy (HR 0.33-0.41), age≥58 years (HR 1.80-1.91), stage III/IV (HR 3.36-13.34), and adnexal metastasis (HR 2.06-5.02) in three to four of the six models for OS. Stratified analyses revealed that adjuvant chemoradiation significantly improved outcome compared with adjuvant chemotherapy for stage IA patients with lymphovascular space invasion and stage IB-IV, lymph node metastasis, and adnexal metastasis. CONCLUSION: Adjuvant chemoradiation was confirmed as an independent good prognostic factor, while older age, stage III/IV, and adnexal metastasis were associated with poor outcome in UCS.
Assuntos
Carcinossarcoma , Neoplasias Uterinas , Idoso , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
BACKGROUND/PURPOSE: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. METHODS: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). RESULTS: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8-25.2] vs recurrence group: 43.6 months [range, 7.1-217.8]; p < 0.001). Patients with solitary recurrence had significantly better SAR than those with disseminated relapse (median: not reached vs 10.4 months, p < 0.001). On multivariate analysis, six models each for SAR and CSS were formulated alternatively including highly correlated variables for the recurrence group. Of these models, solitary relapse pattern (HR: 0.07, p < 0.001), progression-free interval (PFI) > 12 months (HR: 0.22-0.40, p = 0.001 and p = 0.023), CA125 < 35 U/mL at initial recurrence (HR: 0.32, p = 0.007), and overall salvage treatment including radiotherapy (HR: 0.19, p = 0.001) were significant predictors of favorable SAR. The same significant predictors were selected for CSS. CONCLUSION: Recurrent OCCC can be treated with curative intent if the relapse is solitary and can be completely resected or encompassed with radiotherapy, whereas novel therapies are needed for disseminated relapse or progression during primary treatment.
Assuntos
Adenocarcinoma de Células Claras/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida , Taiwan , Falha de TratamentoRESUMO
BACKGROUND/PURPOSE: To compare the clinical outcomes of Taiwanese patients with ovarian clear cell carcinomas (CCCs) and serous carcinomas (SCs). METHODS: We retrieved the clinical records of women with epithelial ovarian cancer (Stage I-IV) who received primary surgeries between 2000 and 2013. Cancer-specific survival (CSS), progression-free survival, and survival after recurrence (SAR) of CCC and SC patients were retrospectively compared. Multivariate analysis was used to identify the independent predictors of survival. RESULTS: Of 891 women diagnosed with epithelial ovarian cancer, 169 CCCs and 351 high-grade SCs were analyzed. The 5-year CSS rates of CCC patients were significantly lower than those of SC for both Stage III (22.3% vs. 47.3%, p = 0.001) and Stage IV (0% vs. 24.4%, p = 0.001) disease. In the absence of gross residual malignancies, the 5-year CSS rate was better for CCC (82.3%) than SC (75.2%, p = 0.010). The 5-year SAR rate was significantly lower for CCC than SC (14.3% vs. 24.4%, p = 0.002). Old age and residual malignancies were independent prognostic factors for CSS in the entire cohort of CCC patients. In the subgroup of Stage I CCC, positive cytology was identified as the only adverse prognostic factor for CSS. CONCLUSION: The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes.
Assuntos
Adenocarcinoma de Células Claras/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Neoplasia Residual/epidemiologia , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Análise de Sobrevida , Taiwan/epidemiologia , Adulto JovemRESUMO
PURPOSE: The aim of this prospective study was to assess the usefulness of (18)F-FDG PET/CT performed before and during treatment for predicting treatment failure in patients with advanced squamous cell carcinoma of the uterine cervix treated with concurrent chemoradiotherapy (CCRT). METHODS: Patients with cervical squamous cell carcinoma, International Federation of Gynecology and Obstetrics stage III/IVA or positive pelvic or paraaortic lymph node (LN) metastasis without other distant metastasis on PET/CT entering a randomized trial of CCRT (AGOG 09-001) were eligible. PET/CT scans were performed at baseline, during week 3 of CCRT and 2 - 3 months after CCRT. PET/CT parameters were correlated with sites of failure and overall survival (OS). The resulting predictors developed from the study cohort were validated on two independent datasets using area under the curve values, sensitivities and specificities. RESULTS: With a median follow-up of 54 months for survivors, 20 (36 %) of the 55 eligible patients were proven to have treatment failure. Sites of failure were local in five, regional in 11, and distant in 11. Four predictors for local failure, three for regional failure, and four for distant failures were identified. After validation with two independent cohorts of 31 and 105 patients, we consider the following as clinically useful predictors: pretreatment metabolic tumour volume (MTV) and during-treatment cervical tumour MTV for local failure; during-treatment SUVnode (maximum standardized uptake value of LNs) for regional and distant failure, and during-treatment MTV for distant failure. During-treatment SUVnode (P = .001) and cervical tumour MTVratio (P = .004) were independent significant predictors of OS by stepwise Cox regression. CONCLUSION: PET/CT imaging before and during treatment is useful for predicting failure sites and OS, making tailored therapeutic modifications feasible with potential outcome improvement during primary therapy.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Feminino , Fluordesoxiglucose F18 , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
BACKGROUND/PURPOSE: Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. METHODS: Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. RESULTS: Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find two CIN2+. Another two cases of CIN2+ were identified from a national registry database. The cost of direct mailing self-samplers was less than that done on request (from NT$434,866 to NT$164,229, response rate of 5% to 15%, respectively, versus NT$683,957 for detecting 1 CIN2+). Reasons for not attending screening included lack of time, embarrassment, assumed low risk, fear of positive results, and perceived potential pain. Among the responders, 90.8% found the method acceptable. CONCLUSION: Our study indicated that different approaches (e.g., direct mailing self-samplers to under-users and/or various educational interventions) must be explored to improve coverage in populations with culture characteristics similar to Taiwan.
Assuntos
Programas de Rastreamento/psicologia , Infecções por Papillomavirus/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Autocuidado/psicologia , Esfregaço Vaginal/psicologia , Adulto , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Teste de Papanicolaou/estatística & dados numéricos , Papillomaviridae , Estudos Prospectivos , Autocuidado/métodos , Inquéritos e Questionários , Taiwan , Esfregaço Vaginal/métodos , Adulto JovemRESUMO
A new poly(aminoester) (EPAE-FA) containing folic acid and amino groups in the backbone and side chain was synthesized. EPAE-FA self-assembled readily with the plasmid DNA (pCMV-ßgal) in HEPES buffer and was characterized by dynamic light scattering, zeta potential, fluorescence images, and XTT cell viability assays. To evaluate the transfection effect of graft ratio of FA on the EPAE system, EPAE-FA polymers with two different graft ratios (EPAE-FA12k and EPAE-FA14k) were also prepared. This study found that all EPAE-FA polymers were able to bind plasmid DNA and yielded positively charged complexes with nano-sized particles (< 200 nm). To assess the transfection efficiency mediated by EPAE and EPAE-FA polymers, we performed in vitro transfection activity assays using FR-negative (COS-7) and FR-positive (HeLa) cells. The EPAE-FA12k/DNA and EPAE-FA14k/DNA complexes were able to transfect HeLa cell in vitro with higher transfection efficiency than PEI25k/DNA at the similar weight ratio. These results demonstrated that the introduction of FA into EPAE system had a significant effect on transferring ability for FR-positive cells (HeLa). Examination of the cytotoxicity of PEI25k and EPAE-FA system revealed that EPAE-FA system had lower cytotoxicity. In this paper, EPAE-FA seemed to be a novel cationic poly(aminoester) for gene delivery and an interesting candidate for further study.
Assuntos
Ácido Fólico/análogos & derivados , Ácido Fólico/síntese química , Indicadores e Reagentes/síntese química , Poliaminas/síntese química , Transfecção , Animais , Células COS , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , DNA/química , DNA/genética , Eletroforese em Gel de Ágar , Ácido Fólico/toxicidade , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Indicadores e Reagentes/toxicidade , Tamanho da Partícula , Plasmídeos/química , Plasmídeos/genética , Poliaminas/toxicidade , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , TitulometriaRESUMO
Uterine carcinosarcoma (UCS) is a highly aggressive gynecologic malignancy. Recurrent or persistent/progressive disease is usually fatal. We aimed to investigate the management and prognosis of these patients. Clinical records of UCS patients from June 1987 to April 2020 were retrospectively reviewed. The stage was re-assigned with the FIGO 2009 staging system. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Of the 168 patients, 98 experienced treatment failure. The median time to treatment failure (TTF) was 8.1 months (range: 0.0-89.1). The median follow-up time of censored patients was 32.0 months (range: 16.8-170.7). The 5-year SAR rates of those with recurrent or persistent/progressive disease were 7.6%. On multivariate analysis, salvage therapy mainly using radiotherapy (HR 0.27, 95% CI: 0.10-0.71) or chemotherapy (HR 0.41, 95% CI: 0.24-0.72) or chemoradiotherapy (CRT) (HR 0.33, 95% CI: 0.15-0.75) were associated with improved SAR, whereas disseminated recurrence was associated with significantly worse SAR (HR 3.94, 95% CI: 1.67-9.31, p = 0.002). Salvage therapy using radiotherapy or chemotherapy or CRT significantly improved SAR. Surgery significantly improved CSS but not SAR, adjusting for confounding factors.
Assuntos
Carcinossarcoma , Neoplasias Uterinas , Humanos , Feminino , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia , PrognósticoRESUMO
Heterologous prime-boost COVID-19 vaccine strategy may facilitate mass COVID-19 immunization. We reported early immunogenicity and safety outcomes of heterologous immunization with a viral vector vaccine (ChAdOx1) and a spike-2P subunit vaccine (MVC-COV1901) in a participant-blinded, randomized, non-inferiority trial (NCT05054621). A total of 100 healthy adults aged 20-70 years having the first dose of ChAdOx1 were 1:1 randomly assigned to receive a booster dose either with ChAdOx1 (n = 50) or MVC-COV1901 (n = 50) at an interval of 4-6 or 8-10 weeks. At day 28 post-boosting, the neutralizing antibody geometric mean titer against wild-type SARS-CoV-2 in MVC-COV1901 recipients (236 IU/mL) was superior to that in ChAdOx1 recipients (115 IU/mL), with a GMT ratio of 2.1 (95% CI, 1.4 to 2.9). Superiority in the neutralizing antibody titer against Delta variant was also found for heterologous MVC-COV1901 immunization with a GMT ratio of 2.6 (95% CI, 1.8 to 3.8). Both spike-specific antibody-secreting B and T cell responses were substantially enhanced by the heterologous schedule. Heterologous boosting was particularly prominent at a short prime-boost interval. No serious adverse events occurred across all groups. The findings support the use of heterologous prime-boost with ChAdOx1 and protein-based subunit vaccines.
Assuntos
COVID-19 , Vacinas Virais , Adulto , Anticorpos Neutralizantes , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2 , Vacinas de Subunidades Antigênicas , Vacinas SintéticasRESUMO
OBJECTIVE: This study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent good prognostic factor and investigate the impact of treatment modalities to cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC). MATERIALS AND METHODS: Patients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were retrospectively (1993-2014) and prospectively (since 2014) enrolled. DNA extraction from paraffin-embedded tissue (FFPE) specimens was used for HPV genotyping. Those with suspected endometrial origin were excluded for analysis. RESULTS: A total of 354 patients with valid HPV results were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types were HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). The HPV16-negativity rates varied widely across hospitals. 322 patients were eligible for prognostic analyses. By multivariate analysis, advanced stage (HR5.8, 95% confidence interval [CI] 2.1-15.8; HR5.8, 95% CI 1.6-20.5), lymph node metastasis (HR4.6, 95% CI 2.7-7.9; HR7.3, 95% CI 3.8-14.0), and HPV16-positivity (HR0.3, 95% CI 0.1-0.6; HR0.3, 95% CI 0.1-0.9) were independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Stage I patients with primary surgery had better 5-year PFS (82.8% vs 50.0% p = 0.020) and OS (89.3% vs 57.1%, p = 0.017) than those with non-primary surgery, while the propensity scores distribution were similar among the treatment groups. CONCLUSION: This study confirmed that HPV16-positivity was a good prognostic factor for PFS and OS in AD/ASC, and patients seemed to have better outcome with primary surgery than non-primary surgery.
Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Carcinoma Adenoescamoso/terapia , Feminino , Papillomavirus Humano 16/genética , Humanos , Estadiamento de Neoplasias , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is frequently associated with endometriosis. Since serum levels of cancer antigen 125 (CA125) have limited diagnostic and prognostic value in this malignancy, there is an unmet need for reliable and specific biomarkers. Previous findings indicated that alpha 1-antitrypsin isoforms (isoAAT) are significantly increased in the peritoneal fluid of patients with endometriosis. This study was undertaken to examine whether serum isoAAT levels in patients with OCCC differ from those measured in women with endometriosis or benign ovarian tumors. We also investigated whether this biomarker may be useful for predicting survival in OCCC. METHODS: Paired serum samples before and after debulking surgery were collected from 27 patients with OCCC. All sera from patients with endometriosis (n = 44) and benign ovarian tumors (n = 32) were obtained in the pretreatment phase. Serum isoAAT levels were assayed using a proprietary ELISA kit. RESULTS: The highest levels of serum isoAAT (median, range) were identified in patients with OCCC (preoperative values: 160.9 ng/mL, range, 101.4-1098.8 ng/mL), followed by patients with endometriosis (125.0 and 83.4-473.2 ng/mL), and those with benign tumors (125.2 and 60.5-191.3 ng/mL). The differences in serum isoAAT levels between patients with OCCC and benign tumors were significant (p = 0.041). Debulking surgery of OCCC resulted in a significant decrease in serum isoAAT levels compared with the preoperative period (median, 160.9 versus 113.0 ng/mL, respectively, p = 0.012). As for prognostic prediction, we found that none of the nine patients with OCCC and serum isoAAT levels ≤130 ng/mL died of disease. CONCLUSION: Serum isoAAT levels may be diagnostically useful to distinguish OCCC from benign ovarian tumors and could also serve as a potential prognostic marker.
Assuntos
Adenocarcinoma de Células Claras , Neoplasias Ovarianas , Isoformas de Proteínas/sangue , alfa 1-Antitripsina/sangue , Biomarcadores Tumorais , Endometriose/fisiopatologia , Feminino , Humanos , Neoplasias Ovarianas/fisiopatologia , Estudos RetrospectivosRESUMO
OBJECTIVE: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer. STUDY DESIGN: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m2) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles. RESULTS: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively. CONCLUSION: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout.
Assuntos
Terapia Neoadjuvante , Neoplasias Ovarianas , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , PaclitaxelRESUMO
To improve the cytotoxicity of PEI25k and the transfection efficiency of poly(beta-amino ester) with DNA, we synthesized a poly(beta-amino ester), PEDP, bearing ester linkages in the backbone and tertiary amines in the backbone and side chain and prepared a binary mixture, PEDP-PEI25k, using physical blending meyhod. Both poly(beta-amino ester) PEDP and binary mixture PEDP-PEI25k, readily self-assembled with plasmid DNA (pCMV-beta gal) in a HEPES buffer, were characterized by dynamic light scattering. The results reveal that PEDP-PEI25k was able to self-assemble plasmid DNA into PEDP-PEI25k/DNA nano-complexes small enough to enter a cell through endocytosis. Titration studies were performed to determine the buffering capacities of PEDP and PEDP-PEI25k. The COS-7 cell viabilities in the presence of PEDP and PEDP-PEI25k were studied. At low mass ratio of PEDP/PEI25k (1/1), it is found that the transfection curve of PEDP-PEI25k/DNA bearing a maximum peak is similar to that of PEI25k/DNA. In addition, the PEDP-PEI25k/DNA complexes were able to transfect COS-7 cells in vitro with a high efficiency comparable to a well-known gene carrier PEI25k/DNA. The results indicate that binary mixture PEDP-PEI25k is an attractive cationic carrier for gene delivery and an interesting candidate for further study.
Assuntos
Transfecção , Aminas/química , Animais , Células COS , Cátions , Chlorocebus aethiops , DNA/química , DNA/genética , Ésteres , Técnicas de Transferência de Genes , Terapia Genética/métodos , Humanos , Plasmídeos , PolímerosRESUMO
OBJECTIVE: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases. METHODS: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members. RESULTS: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies. CONCLUSIONS: Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama/genética , Feminino , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/genética , Estudos Retrospectivos , TaiwanRESUMO
OBJECTIVES: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Doxorrubicina/análogos & derivados , Quimioterapia de Manutenção/métodos , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma Epitelial do Ovário/mortalidade , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , TaiwanRESUMO
The incidence of uterine rupture through a previous cesarean scar (CS) is declining as a result of a lower parity and fewer options for vaginal birth after cesarean. However, uterine ruptures attributable to other causes that traumatize the myometrium are on the rise. To determine whether changes in the causes of uterine rupture had occurred in recent years, we retrospective retrieved the clinical records of all singletons with uterine rupture observed in the delivery room of a Taiwanese tertiary obstetric center over a 15-year period. The overall uterine rupture rate was 3.8 per 10,000 deliveries. A total of 22 cases in 20 women (with two of them experiencing two episodes). Seven uterine ruptures occurred through a previous cesarean scar (CS ruptures, 32%), 13 through a non-cesarean scar (non-CS ruptures, 59%), whereas the remaining two (9%) were in women who did not previously undergo any surgery. All of the 13 non-CS ruptures were identified in women with a history of laparoscopic procedures to the uterus. Specifically, 10 (76%) occurred after a previous laparoscopic myomectomy, one (8%) following a hysteroscopic myomectomy, and two (16%) after a laparoscopic wedge resection of cornual ectopic pregnancy. Severe bleeding (blood loss >1500 mL) requiring transfusions was more frequent in women who experienced non-CS compared with CS ruptures (10 versus 1 case, respectively, P = 0.024). Patients with a history of endoscopic uterine surgery should be aware of uterine rupture during pregnancy.
Assuntos
Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Ruptura Uterina/epidemiologia , Adulto , Cesárea/efeitos adversos , Cicatriz , Feminino , Humanos , Nascimento Prematuro/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. KEY MESSAGES: Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.
Assuntos
Adenocarcinoma de Células Claras/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genômica , Recombinação Homóloga , Humanos , Perda de Heterozigosidade , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
BACKGROUND: Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS: We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS: Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS: The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01276314. FUNDING: Ministry of Science and Technology of Taiwan.