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1.
JMIR Res Protoc ; 10(1): e24414, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33480862

RESUMO

BACKGROUND: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited. OBJECTIVE: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer. METHODS: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery. RESULTS: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study. CONCLUSIONS: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO. TRIAL REGISTRATION: ClinicalTrials.gov NCT03835793; https://clinicaltrials.gov/ct2/show/NCT03835793. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24414.

2.
J Cardiol ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33229237

RESUMO

BACKGROUND: BRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10-40% life-time risk of ovarian cancer in this population. Although effective, premature and acute menopause induces non-cancer related morbidity in both the short and long term. Little is known about the impact of RRSO on the cardiovascular system. METHODS: This cross-sectional study explored the relationship between time since RRSO and signs of subclinical atherosclerosis, as measured by carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), in 165 BRCA1/2 mutation carriers. All participants, aged 40 to 63 years, underwent RRSO before the age of 45 years, and at least 5 years ago. Cardiovascular risk factors were assessed by questionnaires and a single screening visit. Data were analyzed using linear regression models. RESULTS: Mean CIMT was 692.7 µm (SD 87.0), and mean central PWV 6.40 m/s (SD 1.42). After adjustment for age and several relevant cardiovascular risk factors, time since RRSO was not associated with CIMT (ß=0.68 µm; 95% CI -4.02, 5.38) and PWV (ß=44 mm/s; 95% CI -32, 120). Compared to women of a reference group from the general population, lower systolic blood pressure [mean difference 12 mmHg; 95% confidence interval (CI) 10, 14] was found in BRCA1/2 mutation carriers. CONCLUSIONS: We found that, in BRCA1/2 mutation carriers, at 5 to 24 years follow-up, time since RRSO is not related to development of subclinical atherosclerosis. However, the follow-up period in these relatively young women might have been too short.

3.
Surg Oncol ; 35: 149-155, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32877884

RESUMO

BACKGROUND: Inguinofemoral lymphadenectomy (IFL) is part of the surgical treatment of different malignancies of the genital tract and/or the lower limb including vulvar carcinoma, penile carcinoma and melanoma. IFL is associated with morbidity in up to 85% of the patients. The aims of this MAMBO-IC study (Morbidity And Measurement of the Body) are to study the feasibility of using LigaSure for IFL and to assess the differences in the incidence of short-term complications using LigaSure versus conventional IFL randomized within each individual patient. METHODS: In this multicenter randomized controlled trial (RCT), women diagnosed with squamous cell carcinoma of the vulva with an indication for bilateral IFL were included. It was randomly assigned for which groin the LigaSure was used; the other groin was treated with conventional IFL (sharp/diathermia). We estimated the incidence of ≥1 complication(s) per groin using logistic regression and compared this between the two surgical methods, adjusting for possible confounders. RESULTS: We included 40 groins of 20 patients. The estimated incidence of ≥1 complication(s) was 29% after LigaSure versus 70% after conventional IFL (risk difference 41% (95% CI 19-62), p < 0.001). Patients' reported restriction of daily living activities and maximum pain score were equal for both treatment methods. There were no differences in the surgeon reported workload scores. CONCLUSIONS: This RCT shows that LigaSure for IFL is feasible and associated with significantly less short-term surgical complications compared to conventional IFL. Further studies with a larger sample size are needed to validate our findings. ISRCTN15057626.

5.
Int J Mol Sci ; 21(14)2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664330

RESUMO

Vulvar squamous cell carcinoma (VSCC) originates from the progression of either a high-grade squamous intraepithelial lesion (HSIL) or differentiated-type vulvar intraepithelial neoplasia (dVIN), often in a background of lichen sclerosus (LS). The mechanisms leading to the progression of these premalignant lesions to VSCC are elusive. This study aims to identify pathogenic mutations implicated in VSCC development. Using next-generation sequencing, 38 HSIL, 19 dVIN, 20 LS, of which 10 were solitary lesions and 10 with adjacent VSCC, and 10 VSCC adjacent to LS, were screened for hotspot mutations in 50 genes covered by the Ion AmpliSeq Cancer Hotspot Panel v2 Kit (Thermo Fisher Scientific). Pathogenic mutations of TP53 were the most common genetic alterations identified in 53% and 24% of dVIN and HSIL cases, respectively, followed by CDKN2A (p16) mutated in 42% and 0% of dVIN and HSIL, respectively. Seven (70%) and three (30%) of 10 cases of VSCC associated with LS carried TP53 and CDKN2A mutations, respectively, whereas neither solitary LS nor LS associated with VSCC cases harbored mutations in these genes. It appears that TP53 mutations are early events during VSCC carcinogenesis, being present in both HSIL and dVIN lesions. Our preliminary data do not support a genetic background for the notion of LS as the VSCC premalignant lesion.

6.
Gynecol Oncol ; 158(2): 339-346, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32409160

RESUMO

OBJECTIVE: Uterine serous carcinoma (USC) is presumed to arise from endometrial intra-epithelial carcinoma (EIC), whereas tubo-ovarian high-grade serous carcinomas have similar precursor lesions in the Fallopian tube, i.e. serous tubal intra-epithelial carcinoma (STIC). The presence of Fallopian tube abnormalities and their clonal relationship to the concurrent USC was investigated. METHODS: In this multicenter study, all patients treated for USC between 1992 and 2017 were retrospectively identified. Histopathological diagnosis of USC, EIC and STIC was revised by an expert pathologist. Additionally, all Fallopian tube sections were immunohistochemically stained (p53 and Ki-67). Fallopian tube abnormalities were classified as either p53 signature, serous tubal intra-epithelial lesion (STIL) or STIC. The USCs and Fallopian tube abnormalities were analyzed by targeted next-generation sequencing. RESULTS: In 168 included patients, Fallopian tube abnormalities were found in 27.4% (46/168): p53-signatures in 17.9% (30/168), STILs in 3.0% (5/168) and STICs in 6.5% (11/168). In subgroup analysis, STICs were found in 9.5% (11/115) of patients with at least one section of the fimbriated end embedded. Next-generation sequencing showed identical TP53-mutations in the STIC and corresponding USC. CONCLUSIONS: In conclusion, the presence of Fallopian tube abnormalities was shown in a high percentage of patients with USC, representing either true precursor lesions or metastasized disease.

7.
Int J Cancer ; 147(2): 478-489, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32022266

RESUMO

Synchronous primary endometrial and ovarian cancers (SEOs) represent 10% of all endometrial and ovarian cancers and are assumed to develop as independent entities. We investigated the clonal relationship between endometrial and ovarian carcinomas in a large cohort classified as SEOs or metastatic disease (MD). The molecular profiles were compared to The Cancer Genome Atlas (TCGA) data to explore primary origin. Subsequently, the molecular profiles were correlated with clinical outcome. To this extent, a retrospective multicenter study was performed comparing patients with SEOs (n = 50), endometrial cancer with synchronous ovarian metastasis (n = 19) and ovarian cancer with synchronous endometrial metastasis (n = 20). Targeted next-generation sequencing was used, and a clonality index was calculated. Subsequently, cases were classified as POLE mutated, mismatch repair deficient (MMR-D), TP53-wild-type or TP53-mutated. In 92% of SEOs (46/50), the endometrial and concurrent ovarian carcinoma shared at least one somatic mutation, with a clonality index above 0.95, supporting a clonal origin. The SEO molecular profiles showed striking similarities with the TCGA endometrial carcinoma set. SEOs behaved distinctly different from metastatic disease, with a superior outcome compared to endometrial MD cases (p < 0.001) and ovarian MD cases (p < 0.001). Classification according to the TCGA identified four groups with different clinical outcomes. TP53 mutations and extra-utero-ovarian disease were independent predictors for poor clinical outcome. Concluding, SEOs were clonally related in an overwhelming majority of cases and showed a favorable prognosis. Their molecular profile implied a primary endometrial origin. TP53 mutation and extra-utero-ovarian disease were independent predictors for outcome, and may impact adjuvant systemic treatment planning.

8.
Cancer Genomics Proteomics ; 17(2): 151-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32108037

RESUMO

BACKGROUND/AIM: Differentiated vulvar intraepithelial neoplasia (dVIN) and lichen sclerosus (LS) can give rise to vulvar squamous cell carcinoma (VSCC), but genetic evidence is currently still limited. We aimed to determine genetic abnormalities in VSCC and backtrack these abnormalities in the dVIN and LS lesions. MATERIALS AND METHODS: DNA from VSCC and patient-matched dVIN and LS samples of twelve patients was collected. High-resolution genome-wide copy number analysis was performed and subsequently, we sequenced TP53. RESULTS: Copy number alterations were identified in all VSCC samples. One dVIN lesion presented with three copy number alterations that were preserved in the paired VSCC sample. Targeted sequencing of TP53 identified mutations in five VSCCs. All five mutations were traced back in the dVIN (n=5) or the LS (n=1) with frequencies ranging from 3-19%. CONCLUSION: Our data provide genetic evidence for a clonal relationship between VSCC and dVIN or LS.


Assuntos
Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Líquen Escleroso e Atrófico/genética , Neoplasias Vulvares/diagnóstico por imagem , Neoplasias Vulvares/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade
9.
J Natl Cancer Inst ; 112(2): 161-169, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31076742

RESUMO

BACKGROUND: Women with epithelial ovarian cancer (OC) have a higher chance to benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) therapy if their tumor has a somatic or hereditary BRCA1/2 pathogenic variant. Current guidelines advise BRCA1/2 genetic predisposition testing for all OC patients, though this does not detect somatic variants. We assessed the feasibility of a workflow for universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as a prescreen for PARPi treatment and cancer predisposition testing. METHODS: Formalin-fixed paraffin-embedded tissue was obtained from OC patients in seven hospitals immediately after diagnosis or primary surgery. DNA was extracted, and universal tumor BRCA1/2 testing was then performed in a single site. Diagnostic yield, uptake, referral rates for genetic predisposition testing, and experiences of patients and gynecologists were evaluated. RESULTS: Tumor BRCA1/2 testing was performed for 315 (77.6%) of the 406 eligible OC samples, of which 305 (96.8%) were successful. In 51 of these patients, pathogenic variants were detected (16.7%). Most patients (88.2%) went on to have a genetic predisposition test. BRCA1/2 pathogenic variants were shown to be hereditary in 56.8% and somatic in 43.2% of patients. Participating gynecologists and patients were overwhelmingly positive about the workflow. CONCLUSIONS: Universal tumor BRCA1/2 testing in all newly diagnosed OC patients is feasible, effective, and appreciated by patients and gynecologists. Because many variants cannot be detected in DNA from blood, testing tumor DNA as the first step can double the identification rate of patients who stand to benefit most from PARP inhibitors.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Idoso , Gerenciamento Clínico , Feminino , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
10.
Cochrane Database Syst Rev ; 8: CD012858, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31456223

RESUMO

BACKGROUND: Ovarian cancer has the highest mortality rate of all gynaecological malignancies with an overall five-year survival rate of 30% to 40%. In the past two decades it has become apparent and more commonly accepted that a majority of ovarian cancers originate in the fallopian tube epithelium and not from the ovary itself. This paradigm shift introduced new possibilities for ovarian cancer prevention. Salpingectomy during a hysterectomy for benign gynaecological indications (also known as opportunistic salpingectomy) might reduce the overall incidence of ovarian cancer. Aside from efficacy, safety is of utmost importance, especially due to the preventive nature of opportunistic salpingectomy. Most important are safety in the form of surgical adverse events and postoperative hormonal status. Therefore, we compared the benefits and risks of hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy. OBJECTIVES: To assess the effect and safety of hysterectomy with opportunistic salpingectomy versus hysterectomy without salpingectomy for ovarian cancer prevention in women undergoing hysterectomy for benign gynaecological indications; outcomes of interest include the incidence of epithelial ovarian cancer, surgery-related adverse events and postoperative ovarian reserve. SEARCH METHODS: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two clinical trial registers were searched in January 2019 together with reference checking and contact with study authors. SELECTION CRITERIA: We intended to include both randomised controlled trials (RCTs) and non-RCTs that compared ovarian cancer incidence after hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For assessment of surgical and hormonal safety, we included RCTs that compared hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were ovarian cancer incidence, intraoperative and short-term postoperative complication rate and postoperative hormonal status. Secondary outcomes were total surgical time, estimated blood loss, conversion rate to open surgery (applicable only to laparoscopic and vaginal approaches), duration of hospital admission, menopause-related symptoms and quality of life. MAIN RESULTS: We included seven RCTs (350 women analysed). The evidence was of very low to low quality: the main limitations being a low number of included women and surgery-related adverse events, substantial loss to follow-up and a large variety in outcome measures and timing of measurements.No studies reported ovarian cancer incidence after hysterectomy with opportunistic salpingectomy compared to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For surgery-related adverse events, there were insufficient data to assess whether there was any difference in both intraoperative (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.11 to 3.94; 5 studies, 286 participants; very low-quality evidence) and short-term postoperative (OR 0.13, 95% CI 0.01 to 2.14; 3 studies, 152 participants; very low-quality evidence) complication rates between hysterectomy with opportunistic salpingectomy and hysterectomy without opportunistic salpingectomy because the number of surgery-related adverse events was very low. For postoperative hormonal status, the results were compatible with no difference, or with a reduction in anti-Müllerian hormone (AMH) that would not be clinically relevant (mean difference (MD) -0.94, 95% CI -1.89 to 0.01; I2 = 0%; 5 studies, 283 participants; low-quality evidence). A reduction in AMH would be unfavourable, but due to wide CIs, the postoperative change in AMH can still vary from a substantial decrease to even a slight increase. AUTHORS' CONCLUSIONS: There were no eligible studies reporting on one of our primary outcomes - the incidence of ovarian cancer specifically after hysterectomy with or without opportunistic salpingectomy. However, outside the scope of this review there is a growing body of evidence for the effectiveness of opportunistic salpingectomy itself during other interventions or as a sterilisation technique, strongly suggesting a protective effect. In our meta-analyses, we found insufficient data to assess whether there was any difference in surgical adverse events, with a very low number of events in women undergoing hysterectomy with and without opportunistic salpingectomy. For postoperative hormonal status we found no evidence of a difference between the groups. The maximum difference in time to menopause, calculated from the lower limit of the 95% CI and the natural average AMH decline, would be approximately 20 months, which we consider to be not clinically relevant. However, the results should be interpreted with caution and even more so in very young women for whom a difference in postoperative hormonal status is potentially more clinically relevant. Therefore, there is a need for research on the long-term effects of opportunistic salpingectomy during hysterectomy, particularly in younger women, as results are currently limited to six months postoperatively. This limit is especially important as AMH, the most frequently used marker for ovarian reserve, recovers over the course of several months following an initial sharp decline after surgery. In light of the available evidence, addition of opportunistic salpingectomy should be discussed with each woman undergoing a hysterectomy for benign indication, with provision of a clear overview of benefits and risks.


Assuntos
Histerectomia/métodos , Neoplasias Ovarianas/cirurgia , Salpingectomia/métodos , Feminino , Humanos , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
11.
Histopathology ; 75(3): 413-420, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31021414

RESUMO

AIMS: The depth of invasion is an important prognostic factor for patients with vulvar squamous cell carcinoma (SCC). The threshold of 1 mm distinguishes between FIGO stages IA and ≥IB disease and guides the need for groin surgery. Therefore, high interobserver agreement is crucial. The conventional and the alternative method are described to measure the depth of invasion. The aims of this study were to assess interobserver agreement for classifying the depth of invasion using both methods and to identify pitfalls. METHODS AND RESULTS: Fifty slides of vulvar SCC with a depth of invasion approximately 1 mm were selected, digitally scanned and independently assessed by 10 pathologists working in a referral or oncology centre and four pathologists in training. The depth of invasion was measured using both the conventional and alternative method in each slide and categorised into ≤1 and >1 mm. The percentage of agreement and Light's kappa for multi-rater agreement were calculated, and 95% confidence intervals were calculated by bootstrapping (1000 runs). The agreement using the conventional method was moderate (κ = 0.57, 95% confidence interval = 0.45-0.68). The percentage of agreement among the participating pathologists using the conventional method was 85.0% versus 89.4% using the alternative method. Six pitfalls were identified: disagreement concerning which invasive nest is deepest, recognition of invasive growth and where it starts, curved surface, carcinoma situated on the edge of the tissue block, ulceration and different measurement methods. CONCLUSIONS: Pathologists reached only moderate agreement in determining the depth of invasion in vulvar SCC, without a notable difference between the two measurement methods.


Assuntos
Carcinoma de Células Escamosas/patologia , Estadiamento de Neoplasias/métodos , Patologia Cirúrgica/métodos , Neoplasias Vulvares/patologia , Feminino , Humanos , Estadiamento de Neoplasias/normas , Variações Dependentes do Observador , Patologia Cirúrgica/normas
12.
J Gynecol Oncol ; 30(1): e2, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30479086

RESUMO

OBJECTIVE: To explore current practice and influencing factors on adoption of the opportunistic salpingectomy (OS), particularly regarding the decision making, to eventually enhance the development and implementation of clear guidelines. METHODS: This nationwide cross-sectional survey study was conducted in all hospitals in the Netherlands. An anonymous online survey was sent to gynecologists with special interest in gynecological oncology, gynecological endoscopy or urogynecology and all Dutch gynecology trainees. The survey mainly focused on current practice regarding OS and identification of influencing factors on the level of innovation, organization, healthcare professional and individual patient. RESULTS: The response rate was 348 out of 597 gynecologists (58.3%) and 142 out of 340 trainees (41.8%). Current practice of discussing and performing the OS varied widely, with ovarian cancer (OC) risk reduction as most important supportive factor on innovation level. Supportive factors on the level of organization and healthcare provider were; working in a non-training hospital, knowledge of current literature and extensive work experience (in years and annual number of hysterectomies). On individual patient level, a vaginal approach of hysterectomy, negative family history for OC and the presence of firm adhesions were suppressive factors for the OS. CONCLUSION: In this study we evaluated the current practice regarding the opportunistic salpingectomy in the Netherlands and identified influencing factors on different levels to raise awareness and attribute to development of a targeted implementation strategy, on both national and international level.


Assuntos
Carcinoma Epitelial do Ovário/prevenção & controle , Tomada de Decisão Clínica , Neoplasias Ovarianas/prevenção & controle , Procedimentos Cirúrgicos Profiláticos/psicologia , Salpingectomia/psicologia , Estudos Transversais , Feminino , Ginecologia/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Histerectomia Vaginal/estatística & dados numéricos , Países Baixos , Ovário/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Medição de Risco , Inquéritos e Questionários
13.
J Am Acad Dermatol ; 81(4): 956-962, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30458205

RESUMO

BACKGROUND: Vulvar Paget disease (VPD) is a rare skin disorder that is considered premalignant. OBJECTIVE: To assess the clinical course, treatment schedules, and effect of invasion and treatment on recurrence and survival in patients with VPD. METHODS: Data on women with VPD were retrieved from the medical files and pathology reports in all Dutch tertiary university medical centers. Disease-free survival and 5-year disease-specific survival were estimated by using Kaplan-Meier curves. RESULTS: Data on 113 patients whose VPD was diagnosed between 1991 and 2016 were analyzed; 77% had noninvasive VPD. Most of the women (65%) underwent a surgical procedure. Recurrences were reported in 40%. Of the women with noninvasive VPD, 8% developed invasion. There were no disease-specific deaths reported in the women with noninvasive VPD. The 5-year disease-specific survival rate was greater than 98% in noninvasive and microinvasive VPD, but significantly worse in invasive VPD (50% [P < .0005]). LIMITATIONS: The main limitations of this study are its retrospective character and the fact that original pathology samples were not available for reassessment. CONCLUSIONS: VPD is extremely rare, and the recurrence rates are high. Most patients have noninvasive VPD, which does not affect survival and should be considered a chronic disorder with limited invasive potential. In cases of invasive disease, survival decreases significantly.


Assuntos
Recidiva Local de Neoplasia/patologia , Doença de Paget Extramamária/secundário , Doença de Paget Extramamária/terapia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Imiquimode/uso terapêutico , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Países Baixos , Estudos Retrospectivos , Taxa de Sobrevida , Vulvectomia
14.
Eur J Surg Oncol ; 44(10): 1555-1561, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29934053

RESUMO

INTRODUCTION: The recommended pathological resection margin (8 mm) for vulvar squamous cell carcinoma (SCC) is broader than for SCC located elsewhere, and does not depend on tumor grade or lesion size. Our aim is to evaluate the resection margin in vulvar SCC in relation to local recurrence, and to determine the impact of other prognostic factors. MATERIALS AND METHODS: Data of all surgically treated patients at the Gynecological Oncology Center South with vulvar SCC, FIGO IB-IIIC, between 2005 and 2015 were analysed retrospectively. The relation between the pathological resection margin and other clinicopathological factors with the risk of local recurrence was analysed. RESULTS: In this cohort of 167 patients, the tumor was radically removed in 87% of the patients. Yet, in 57% the pathological resection margin was <8 mm. Including re-excisions, the median closest margin was 7.0 mm. There was no significant difference in the risk of local recurrence for a resection margin <8 mm or ≥8 mm (25.0% (n = 20) and 22.2% (n = 16)), nor in the median resection margin of patients with or without local recurrence (6.5 mm and 7.0 mm). Lichen sclerosus was the only significant risk factor for local recurrence. CONCLUSION: A pathological resection margin <8 mm was not related to an increased risk of local recurrence. The most important predictor of local recurrence was the presence of lichen sclerosus. A resection margin <8 mm in vulvar SCC can therefore be accepted, especially in tumors located close to clitoris, urethra or anus.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/etiologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Carga Tumoral , Líquen Escleroso Vulvar/complicações , Neoplasias Vulvares/complicações
15.
Cancer ; 124(5): 952-959, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29315498

RESUMO

BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for BRCA1/2 mutation carriers because of their increased risk of ovarian carcinoma. Despite RRSO, metachronous peritoneal carcinomatosis occasionally is diagnosed. METHODS: The literature was searched for BRCA1/2 mutation carriers with peritoneal carcinomatosis after risk-reducing surgery. The authors were asked for additional data. Clinical and histopathological data were descriptively analyzed. Cases were compared with a single-institution control cohort. RESULTS: Of 36 cases, 86.1% concerned BRCA1 mutation carriers. The median age of the patients was 52 years (range, 30-71 years) at the time of risk-reducing surgery and 60 years (range, 37-75 years) at the time of diagnosis of peritoneal carcinomatosis. The median interval between the 2 events was 54.5 months (range, 11-292 months). Peritoneal carcinomatosis was mostly high-grade serous carcinoma. Histopathological details of the RRSO specimens were retrieved in 8 cases; 5 (62.5%) were found to have serous tubal intraepithelial carcinoma and 1 had epithelial atypia. Cases were older (P = .025) at the time of risk-reducing surgery and harbored more serous tubal intraepithelial carcinomas (P<.001) compared with women from the control cohort. CONCLUSIONS: Metachronous peritoneal carcinomatosis after risk-reducing surgery occurs predominantly in BRCA1 mutation carriers, usually within 5 years. Data have suggested that surgery at a younger age lowers the rates of peritoneal carcinomatosis. These data can be used in the gynecologic counseling of BRCA1/2 mutation carriers. RRSO should include complete salpingectomy. Detailed histopathological examination of specimens removed during RRSO is essential. Cancer 2018;124:952-9. © 2018 American Cancer Society.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação , Neoplasias Peritoneais/diagnóstico , Salpingo-Ooforectomia/métodos , Adulto , Idoso , Feminino , Heterozigoto , Humanos , Pessoa de Meia-Idade , Neoplasias Peritoneais/etiologia , Fatores de Risco , Salpingo-Ooforectomia/efeitos adversos
16.
Maturitas ; 108: 13-17, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29290209

RESUMO

OBJECTIVES: To reduce the risk of ovarian cancer, BRCA1/2 mutation carriers are advised to undergo salpingo-oophorectomy (RRSO) around the age of 40 years. This may induce severe climacteric symptoms, potentially lowering their quality of life. Personal positive resources such as physical fitness and self-compassion may help women to deal with these symptoms. We investigated the association of climacteric symptoms with self-compassion and physical fitness in oophorectomized BRCA1/2 mutation carriers. STUDY DESIGN: A cross-sectional study was conducted in 165 BRCA1/2 mutation carriers, aged 40-63 years, who underwent an RRSO at age 45 years or younger and at least 5 years previously. MAIN OUTCOME MEASURES: Climacteric symptoms were measured by the Greene Climacteric Scale. Self-compassion was rated using the Self-Compassion Scale-Short Form, and physical fitness using the Duke Activity Status Index. RESULTS: BRCA1/2 mutation carriers reported low levels of climacteric symptoms (mean 10.28 [SD 6.45], and being highly self-compassionate and physically fit. After adjustment for possible covariates, higher self-compassion (ß=-1.65, 95% CI -2.46, -0.84) and physical fitness (ß=-0.25, 95% CI -0.34, -0.16) were associated with fewer climacteric symptoms. Current smoking was independently associated with more climacteric symptoms (ß=2.66, 95% CI 0.26, 5.07). CONCLUSIONS: Being self-compassionate and physically fit were associated with fewer climacteric symptoms. Future research is needed to investigate the effect of training in self-compassion and physical fitness on climacteric symptoms in BRCA1/2 mutation carriers.


Assuntos
Empatia , Menopausa/fisiologia , Ovariectomia , Aptidão Física , Adulto , Estudos Transversais , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/prevenção & controle , Qualidade de Vida , Risco
17.
Health Expect ; 21(3): 659-667, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29281161

RESUMO

BACKGROUND: BRCA1/2 mutation carriers' choice between risk-reducing salpingo-oophorectomy (RRSO) and salpingectomy with delayed oophorectomy is very complex. Aim was to develop a patient decision aid that combines evidence with patient preferences to facilitate decision making. DESIGN: Systematic development of a patient decision aid in an iterative process of prototype development, alpha testing by patients and clinicians and revisions using International Patient Decision Aid Standards (IPDAS) quality criteria. Information was based on the available literature and current guidelines. A multidisciplinary steering group supervised the process. SETTING AND PARTICIPANTS: Pre-menopausal BRCA1/2 mutation carriers choosing between RRSO and salpingectomy with delayed oophorectomy in Family Cancer Clinics in the Netherlands. MAIN OUTCOME MEASURES: IPDAS quality criteria, relevance, usability, clarity. RESULTS: The patient decision aid underwent four rounds of alpha testing and revisions. Finally, two paper decision aids were developed: one for BRCA1 and one for BRCA2. They both contained a general introduction, three chapters and a step-by-step plan containing a personal value clarification worksheet. During alpha testing, risk communication and information about premature menopause and hormone therapy were the most revised items. The patient decision aids fulfil 37 of 43 (86%) IPDAS criteria for content and development process. DISCUSSION AND CONCLUSIONS: Both BRCA1/2 mutation carriers and professionals are willing to use or offer the developed patient decision aids for risk-reducing surgery. The patient decision aids have been found clear, balanced and comprehensible. Future testing among patients facing the decision should point out its effectiveness in improving decision making.


Assuntos
Neoplasias da Mama , Técnicas de Apoio para a Decisão , Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias Ovarianas , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Países Baixos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Ovariectomia/métodos , Comportamento de Redução do Risco , Salpingectomia/métodos
18.
Gynecol Oncol ; 148(3): 622-631, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29137809

RESUMO

BACKGROUND: In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to local recurrences should be helpful to select high risk patients and/or to develop strategies to prevent local recurrences. OBJECTIVE: This systematic review aims to evaluate the current knowledge on the incidence of local recurrences in vulvar carcinoma related to clinicopathologic and cell biologic variables. DATA SOURCES: Relevant studies were identified by an extensive online electronic search in July 2017. STUDY ELIGIBILITY CRITERIA: Studies reporting prognostic factors specific for local recurrences of vulvar carcinoma were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Two review authors independently performed data selection, extraction and assessment of study quality. The risk difference was calculated for each prognostic factor when described in two or more studies. RESULTS: Twenty-two studies were included; most of all were retrospective and mainly reported pathologic prognostic factors. Our review indicates an estimated annual local recurrence rate of 4% without plateauing. The prognostic relevance for local recurrence of vulvar carcinoma of all analyzed variables remains equivocal, including pathologic tumor free margin distance <8mm, presence of lichen sclerosus, groin lymph node metastases and a variety of primary tumor characteristics (grade of differentiation, tumor size, tumor focality, depth of invasion, lymphovascular space invasion, tumor localization and presence of human papillomavirus). CONCLUSIONS: Current quality of data on prognostic factors for local recurrences in vulvar carcinoma patients does not allow evidence-based clinical decision making. Further research on prognostic factors, applying state of the art methodology is needed to identify high-risk patients and to develop alternative primary and secondary prevention strategies.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Linfonodos/patologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Vulvares/cirurgia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Feminino , Virilha , Procedimentos Cirúrgicos em Ginecologia , Humanos , Metástase Linfática , Margens de Excisão , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Infecções por Papillomavirus/epidemiologia , Prognóstico , Fatores de Risco , Líquen Escleroso Vulvar/epidemiologia , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/patologia
19.
Expert Rev Anticancer Ther ; 17(7): 615-624, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28608762

RESUMO

INTRODUCTION: Inguinofemoral lymphadenectomy (IFL) is performed in the treatment for vulvar cancer. One or more complications after IFL is reported in up to 85% of the patients. This review presents an overview of surgical techniques and peri- and post-operative care that has been studied in order to reduce the morbidity associated with IFL in vulvar cancer patients. Areas covered: Current knowledge on post-operative complications after different surgical techniques and peri- and post-operative protocols were discussed. A systematic literature review was conducted using MEDLINE, EMBASE and the Cochrane library on 20 February 2017. In order to be eligible for inclusion, studies must report the associated post-operative morbidity per surgical technique, or peri- or post-operative care given after IFL in vulvar cancer patients. Expert commentary: After the implementation of several new surgical techniques, the morbidity after IFL decreased but remains high and clinically meaningful. More research is needed on surgical techniques and peri-or post-operative care to further reduce the complication rates after IFL in vulvar cancer patients.


Assuntos
Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias Vulvares/patologia , Feminino , Humanos , Canal Inguinal , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Cuidados Pós-Operatórios/métodos
20.
Hum Pathol ; 68: 184-188, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28461034

RESUMO

Vulvar Paget disease is a rare skin disorder, considered an in situ adenocarcinoma. It is characterized by intraepithelial Paget cells, of which the origin is unclear. About 75% of cases have a cutaneous origin; the other 25% originate from an intestinal or urological malignancy. We report the first case of retrograde pagetoid spread from a rectal adenocarcinoma to the vulva and cervix. A 66-year-old woman presented with postmenopausal bleeding and a history of Crohn disease. Gynecological workup revealed vulvar and endocervical lesions consisting of Paget cells and adenocarcinoma, respectively. A rectal adenocarcinoma with in situ adenocarcinoma was diagnosed. The surgical specimen demonstrated Paget cells in the squamous epithelium of the anus and vulva. Immunohistochemistry demonstrated an intestinal phenotype of these cells. Genetic testing revealed the same TP53 mutation in tumor cells of the rectal adenocarcinoma and vulvar and endocervical lesions, demonstrating that the Paget cells originated from the same intestinal tumor.


Assuntos
Adenocarcinoma/secundário , Doença de Paget Extramamária/secundário , Neoplasias Retais/patologia , Neoplasias do Colo do Útero/secundário , Neoplasias Vulvares/secundário , Adenocarcinoma/química , Adenocarcinoma/genética , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Mutação , Doença de Paget Extramamária/química , Doença de Paget Extramamária/genética , Neoplasias Retais/química , Neoplasias Retais/genética , Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/genética , Neoplasias Vulvares/química , Neoplasias Vulvares/genética
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