RESUMEN
OBJECTIVE: The aim of this study was to describe the long-term outcome of asymptomatic BRCA1/2 germline pathogenic variant (GPV) carriers with high-grade serous carcinoma (HGSC) in their risk-reducing salpingo-oophorectomy (RRSO) specimen. METHODS: In a previously described cohort of asymptomatic BRCA1/2 GPV carriers derived from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study, women with HGSC at RRSO were identified. Main outcome was ten-year disease-free survival (DFS). Secondary outcomes were time to recurrence, ten-year disease-specific survival (DSS), ten-year overall survival (OS). Patient, disease and treatment characteristics associated with recurrence were described. RESULTS: The 28 included women with HGSC at RRSO were diagnosed at a median age of 55.3 years (range: 33.5-74.3). After staging, eighteen women had (FIGO) stage I, three stage II and five had stage III disease. Two women did not undergo surgical staging and were classified as unknown stage. After a median follow-up of 13.5 years (range: 9.1-24.7), six women with stage I (33%), one woman with stage II (33%), two women with stage III (40%) and none of the women with unknown stage developed a recurrence. Median time to recurrence was 6.9 years (range: 0.8-9.2 years). Ten-year DFS was 68%, ten-year DSS was 88% and ten-year OS was 82%. CONCLUSION: Most asymptomatic BRCA1/2 GPV carriers with HGSC at RRSO were diagnosed at an early stage. Nevertheless, after a median follow-up of 13.5 years, nine of the 28 women with HGSC at RRSO developed a recurrence after a median of 6.9 years.
Asunto(s)
Cistadenocarcinoma Seroso , Mutación de Línea Germinal , Neoplasias Ováricas , Salpingooforectomía , Humanos , Femenino , Persona de Mediana Edad , Adulto , Anciano , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Proteína BRCA2/genética , Proteína BRCA1/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/prevención & control , Genes BRCA2 , Supervivencia sin Enfermedad , Genes BRCA1 , Heterocigoto , Clasificación del TumorRESUMEN
OBJECTIVE: This study aimed to assess the outcomes of patients with early stage mucinous ovarian carcinoma based on subtype (expansile vs infiltrative). METHODS: We retrospectively analyzed all surgically treated patients with mucinous ovarian carcinoma in the Netherlands (2015-2020), using data from national registries. Subtypes were determined, with any ambiguities resolved by a dedicated gynecologic pathologist. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I were categorized into full staging, fertility-sparing, or partial stagings. Outcomes were overall survival and recurrence free survival, and recurrence rates. RESULTS: Among 409 identified patients, 257 (63%) had expansile and 152 (37%) had infiltrative tumors. Patients with expansile tumors had FIGO stage I more frequently (n=243, 95% vs n=116, 76%, p<0.001). For FIGO stage I disease, patients with expansile and infiltrative tumors underwent similar proportions of partial (n=165, 68% vs n=78, 67%), full (n=32, 13% vs n=23, 20%), and fertility-sparing stagings (n=46, 19% vs n=15, 13%) (p=0.139). Patients with expansile FIGO stage I received less adjuvant chemotherapy (n=11, 5% vs n=24, 21%, p<0.001), exhibited better overall and recurrence free survival (p=0.006, p=0.012), and fewer recurrences (n=13, 5% vs n=16, 14%, p=0.011). Survival and recurrence rates were similar across the expansile extent of staging groups. Patients undergoing fertility-sparing staging for infiltrative tumors had more recurrences compared with full or partial stagings, while recurrence free survival was similar across these groups. Full staging correlated with better overall survival in infiltrative FIGO stage I (p=0.022). CONCLUSIONS: While most patients with FIGO stage I underwent partial staging, those with expansile had better outcomes than those with infiltrative tumors. Full staging was associated with improved overall survival in infiltrative, but not in expansile FIGO stage I. These results provide insight for tailored surgical approaches.
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Adenocarcinoma Mucinoso , Estadificación de Neoplasias , Neoplasias Ováricas , Humanos , Femenino , Países Bajos/epidemiología , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidad , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Adulto , Estudios de Cohortes , Anciano , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiologíaRESUMEN
BACKGROUND: Up to 40% of vulvar cancer patients present with local recurrence within 10 years of follow-up. An inguinofemoral lymphadenectomy (IFL) is indicated if not performed at primary treatment. The incidence and risk factors for lymph node metastases (LNM) at first local recurrence, however, are unclear. Our aim was to determine the incidence of LNM at first local recurrence, in relation to previous groin treatment and clinicopathological factors. METHODS: A multicenter cohort study including vulvar cancer patients with a first macroinvasive local recurrence after primary surgical treatment between 2000 and 2015 was conducted in the Netherlands. Groin status at local recurrence was defined as positive (N+), negative (N-) or unknown (N?) and based on histology, imaging and follow-up. Patient-, tumour- and treatment characteristics of primary and recurrent disease were analysed. RESULTS: Overall, 16.3% (66/404) had a N+ groin status at first local recurrence, 66.4% (268/404) N- and 17.3% (70/404) N? groin status. The incidence of a N+ groin status was comparable after previous SLN and IFL, 11.5% and 13.8%, respectively. A N+ groin status was related to tumour size (25 vs.12 mm; P < 0.001), depth of invasion (5 vs. 3 mm; P < 0.001) and poorly differentiated tumours (22.9 vs. 11.9%; P = 0.050) at local recurrence. CONCLUSIONS: The incidence of LNM at first local recurrence in vulvar cancer patients was 16.3%, and independent of previous type of groin surgery. In accordance with primary diagnosis, tumour size, depth of invasion, and tumour grade were significantly associated with a positive groin status.
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Neoplasias de la Vulva , Femenino , Humanos , Metástasis Linfática/patología , Neoplasias de la Vulva/epidemiología , Neoplasias de la Vulva/cirugía , Neoplasias de la Vulva/patología , Estudios de Cohortes , Incidencia , Recurrencia Local de Neoplasia/patología , Escisión del Ganglio Linfático/efectos adversos , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure 1 to 3 years after a premenopausal oophorectomy. However, the long-term effects of premenopausal oophorectomy on sexual functioning are unknown. OBJECTIVE: This study aimed to study long-term sexual functioning in women at increased familial risk of breast or ovarian cancer who underwent a risk-reducing salpingo-oophorectomy either before the age of 46 years (premenopausal group) or after the age of 54 years (postmenopausal group). Subgroup analyses were performed in the premenopausal group, comparing early (before the age of 41 years) and later (at ages 41-45 years) premenopausal risk-reducing salpingo-oophorectomy. STUDY DESIGN: Between 2018 and 2021, 817 women with a high familial risk of breast or ovarian cancer from an ongoing cohort study were invited to participate in our study. Because of a large difference in age in the study between the premenopausal and postmenopausal salpingo-oophorectomy groups, we restricted the comparison of sexual functioning between the groups to 368 women who were 60 to 70 years old at completion of the questionnaire (226 in the premenopausal group and 142 in the postmenopausal group). In 496 women with a premenopausal risk-reducing salpingo-oophorectomy, we compared the sexual functioning between women in the early premenopausal group (n=151) and women in the later premenopausal group (n=345). Differences between groups were analyzed using multiple regression analyses, adjusting for current age, breast cancer history, use of hormone replacement therapy, body mass index, chronic medication use (yes or no), and body image. RESULTS: Mean times since risk-reducing salpingo-oophorectomy were 20.6 years in the premenopausal group and 10.6 years in the postmenopausal group (P<.001). The mean age at questionnaire completion was 62.7 years in the premenopausal group, compared with 67.0 years in the postmenopausal group (P<.001). Compared with 48.9% of women in the postmenopausal group, 47.4% of women in the premenopausal group were still sexually active (P=.80). Current sexual pleasure scores were the same for women in the premenopausal group and women in the postmenopausal group (mean pleasure score, 8.6; P=.99). However, women in the premenopausal group more often reported substantial discomfort than women in the postmenopausal group (35.6% vs 20.9%; P=.04). After adjusting for confounders, premenopausal risk-reducing salpingo-oophorectomy was associated with substantially more discomfort during sexual intercourse than postmenopausal risk-reducing salpingo-oophorectomy (odds ratio, 3.1; 95% confidence interval, 1.04-9.4). Moreover, after premenopausal risk-reducing salpingo-oophorectomy, more severe complaints of vaginal dryness were observed (odds ratio, 2.6; 95% confidence interval, 1.4-4.7). Women with a risk-reducing salpingo-oophorectomy before the age of 41 years reported similar pleasure and discomfort scores as women with a risk-reducing salpingo-oophorectomy between ages 41 and 45 years. CONCLUSION: More than 15 years after premenopausal risk-reducing salpingo-oophorectomy, the proportion of sexually active women was comparable with the proportion of sexually active women with a postmenopausal risk-reducing salpingo-oophorectomy. However, after a premenopausal risk-reducing salpingo-oophorectomy, women experienced more vaginal dryness and more often had substantial sexual discomfort during sexual intercourse. This did not lead to less pleasure with sexual activity.
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Neoplasias Ováricas , Salpingooforectomía , Femenino , Humanos , Persona de Mediana Edad , Adulto , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Genes BRCA1 , Genes BRCA2 , Ovariectomía , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & controlRESUMEN
OBJECTIVE: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years after RRSO. DESIGN: A cross-sectional study with prospective follow-up, nested in a nationwide cohort. SETTING: Multicentre in the Netherlands. POPULATION OR SAMPLE: 641 women (66% BRCA1/2 pathogenic variant carriers) who underwent either a premenopausal RRSO ≤ age 45 (n = 436) or a postmenopausal RRSO ≥ age 54 (n = 205). All participants were older than 55 years at recruitment. METHODS: Participants completed an online cognitive test battery and a questionnaire on subjective cognition. We used multivariable regression analyses, adjusting for age, education, breast cancer, hormone replacement therapy, cardiovascular risk factors and depression. MAIN OUTCOME MEASURES: The influence of RRSO on objective and subjective cognition of women with a premenopausal RRSO compared with women with a postmenopausal RRSO. RESULTS: After adjustment, women with a premenopausal RRSO (mean time since RRSO 18.2 years) performed similarly on objective cognitive tests compared with women with a postmenopausal RRSO (mean time since RRSO 11.9 years). However, they more frequently reported problems with reasoning (odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.1-3.1) and multitasking (OR 1.9, 95% CI 1.1-3.4) than women with a postmenopausal RRSO. This difference between groups disappeared in an analysis restricted to women of comparable ages (60-70 years). CONCLUSIONS: Reassuringly, approximately 18 years after RRSO, we found no association between premenopausal RRSO and objective cognition.
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Neoplasias Ováricas , Salpingooforectomía , Femenino , Humanos , Persona de Mediana Edad , Proteína BRCA1/genética , Proteína BRCA2/genética , Cognición , Estudios Transversales , Predisposición Genética a la Enfermedad , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Ovariectomía , Estudios Prospectivos , Salpingooforectomía/efectos adversos , AdultoRESUMEN
OBJECTIVE: Complication rates after cytoreductive surgery are important quality indicators for hospitals that treat patients with advanced-stage ovarian cancer. Case-mix factors are patient and tumor characteristics that may influence hospital outcomes such as the complication rates. Currently, no case-mix adjustment model exists for complications after cytoreductive surgery; therefore, it is unclear whether hospitals are being compared correctly. This study aims to develop the first case-mix adjustment model for complications after surgery for advanced-stage ovarian cancer, enabling an accurate comparison between hospitals. METHODS: This population-based study included all patients undergoing cytoreductive surgery for advanced-stage ovarian cancer registered in the Netherlands in 2017-2019. Case-mix variables were identified and assessed using logistic regressions. The primary outcome was the composite outcome measure 'complicated course'. Patients had a complicated course when at least one of the following criteria were met: (1) any complication combined with a prolonged length of hospital stay; (2) complication requiring reintervention; (3) any complication with a prolonged length of stay in the intensive care unit; or (4) 30-day mortality or in-hospital mortality during admission following surgery. Inter-hospital variation was analyzed using univariable and multivariable logistic regressions and visualized using funnel plots. RESULTS: A total of 1822 patients were included, of which 10.7% (n=195) had a complicated course. Comorbidity and tumor stage had a significant impact on complicated course rates in multivariable logistic regression. Inter-hospital variation was not significant for case-mix factors. Complicated course rates ranged between 2.2% and 29.1%, and case-mix adjusted observed/expected ratios ranged from 0.20 to 2.67 between hospitals. Three hospitals performed outside the confidence intervals for complicated course rates. These hospitals remained outliers after case-mix adjustment. CONCLUSION: There is variation between hospitals regarding complicated course rates after cytoreductive surgery for ovarian cancer in the Netherlands. While comorbidity and tumor stage significantly affected the complicated course rates, adjusting for case-mix factors did not significantly affect hospital outcomes. The limited impact of case-mix adjustment could be a result of the Dutch centralized healthcare model.
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Neoplasias Ováricas , Indicadores de Calidad de la Atención de Salud , Humanos , Femenino , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Hospitales , Neoplasias Ováricas/cirugía , Carcinoma Epitelial de Ovario/cirugíaRESUMEN
INTRODUCTION: Opportunistic salpingectomy (OS) refers to additional removal of the fallopian tubes during abdominal surgery performed for another medical indication, as prevention for ovarian cancer. As OS has been inconsistently implemented, its clinical practice varies worldwide. To reduce this variation, insight is required into current clinical practice and its determinants. Therefore, the study aim was to determine the implementation of counseling and performance of OS between 2015 and 2018, and its patient, surgical, physician, and hospital characteristics. MATERIAL AND METHODS: Retrospective study using electronic medical records from six different Dutch hospitals: two academic, two large teaching, and two non-teaching hospitals. Patients were considered eligible for OS if they underwent elective non-obstetric abdominal surgery for a gynecological indication from January 2015 through December 2018. Primary outcomes were uptake of counseling and performance of OS. Multilevel multivariable logistic regression analyses were conducted to identify characteristics associated with OS. RESULTS: A total of 3214 patients underwent elective non-obstetric abdominal surgery for a gynecological indication and were eligible for OS. Counseling on OS increased significantly from 2.9% in 2015 to 29.4% in 2018. In this period, 440 patients were counseled on OS, of which 95.9% chose OS. Performance of OS increased significantly from 6.9% in 2015 to 44.5% in 2018. Counseling for and performance of OS were more likely in patients who had surgery by laparoscopic approach, were counseled by a gynecological resident, or had more than three contact moments before surgery. Additionally, OS was less likely in patients who had vaginal surgery. CONCLUSIONS: Although the uptake of OS increased from 2015 to 2018, the majority of patients who were eligible for OS were not counseled and did not undergo OS. Its clinical practice varies on patient, surgery, and physician characteristics. Therefore, an implementation strategy tailored to associated determinants is recommended.
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Ginecología , Neoplasias Ováricas , Humanos , Femenino , Histerectomía , Estudios Retrospectivos , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/cirugía , SalpingectomíaRESUMEN
BACKGROUND: Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly when no lymphadenectomy is performed. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH), both without lymphadenectomy, for early-stage endometrial cancer up to 5 years postoperatively. METHODS: Follow-up of a multi-centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, grade, and radiotherapy with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. To test for significance, non-inferiority margins were defined. RESULTS: In total, 279 women underwent a surgical procedure, of whom 263 (94%) had follow-up data. For the TLH (n = 175) and TAH (n = 88) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.69; 95%CI, 0.31-1.52), OS (89.2% vs 82.8%; aHR[death], 0.60; 95%CI, 0.30-1.19), and DSS (95.0% vs 89.8%; aHR[death], 0.62; 95%CI, 0.23-1.70) were reported at 5 years. At a 10% significance level, and with a non-inferiority margin of 0.20, the null hypothesis of inferiority was rejected for all three outcomes. There were no port-site or wound metastases, and local recurrence rates were comparable. CONCLUSION: Disease recurrence and 5-year survival rates were comparable between the TLH and TAH groups and comparable to studies with lymphadenectomy, supporting the widespread use of TLH without lymphadenectomy as the primary treatment for early-stage, low-grade endometrial cancer.
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Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/cirugía , Histerectomía/métodos , Recurrencia Local de Neoplasia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Humanos , Laparoscopía/métodos , Laparotomía/métodos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Radioterapia AdyuvanteRESUMEN
OBJECTIVE: High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers undergoing surgery to prevent ovarian cancer, and identified factors associated with high cancer worry. METHODS: Cancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose either novel risk-reducing salpingectomy with delayed oophorectomy or standard risk-reducing salpingo-oophorectomy. The Cancer Worry Scale was obtained before and 3 and 12 months after surgery. Cancer worry patterns were analysed using latent class growth analysis and associated factors were identified with regression analysis. RESULTS: Of all 577 BRCA1/2-PV carriers, 320 (57%) had high (≥ 14) cancer worry pre-surgery, and 54% had lower worry 12 months post-surgery than pre-surgery. Based on patterns over time, BRCA1/2-PV carriers could be classified into three groups: persistently low cancer worry (56%), persistently high cancer worry (6%), and fluctuating, mostly declining, cancer worry (37%). Factors associated with persistently high cancer concerns were age below 35 (BRCA1) or 40 (BRCA2), unemployment, previous breast cancer, lower education and a more recent BRCA1/2-PV diagnosis. CONCLUSIONS: Some degree of cancer worry is considered normal, and most BRCA1/2-PV carriers have declining cancer worry after gynaecological risk-reducing surgery. However, a subset of these BRCA1/2-PV carriers has persisting major cancer concerns up to 1 year after surgery. They should be identified and potentially offered additional support. CLINICAL TRIAL REGISTRATION: The TUBA-study is registered at ClinicalTrials.gov since December 11th, 2014. Registration number: NCT02321228.
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Neoplasias de la Mama , Neoplasias Ováricas , Proteína BRCA1/genética , Femenino , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Estudios Prospectivos , Salpingectomía , SalpingooforectomíaRESUMEN
OBJECTIVE: Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment. METHODS: Women diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2-IVA cervical cancer with lymph nodes ≥1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis. RESULTS: Of 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83). CONCLUSIONS: This study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors.
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Neoplasias del Cuello Uterino , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
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.
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Recurrencia Local de Neoplasia/patología , Enfermedad de Paget Extramamaria/secundario , Enfermedad de Paget Extramamaria/terapia , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Imiquimod/uso terapéutico , Estimación de Kaplan-Meier , Metástasis Linfática , Persona de Mediana Edad , Invasividad Neoplásica , Países Bajos , Estudios Retrospectivos , Tasa de Supervivencia , VulvectomíaRESUMEN
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.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Mutación , Neoplasias Peritoneales/diagnóstico , Salpingooforectomía/métodos , Adulto , Anciano , Femenino , Heterocigoto , Humanos , Persona de Mediana Edad , Neoplasias Peritoneales/etiología , Factores de Riesgo , Salpingooforectomía/efectos adversosRESUMEN
BACKGROUND: Spread of evidence-based innovations beyond pioneering settings is essential to improve quality of care. This study aimed to evaluate the influence of a national project to implement 'Enhanced Recovery After Surgery' (ERAS) among colorectal teams on the spread of this innovation to gynaecological procedures. METHODS: A retrospective observational multicentre study was performed of a consecutive sample of patients who underwent major elective gynaecological surgery in 2012-2013. Ten Dutch hospitals (294 patients) had participated in a colorectal breakthrough project implementing ERAS on a nationwide basis and were assigned to the intervention group. Thirteen hospitals (390 patients) that had not participated in this project acted as controls. Outcome measures were time to functional recovery and total length of postoperative hospital stay. Multilevel models adjusted for clustering and baseline demographics were used for analysis. The uptake of ten selected perioperative care elements was evaluated for each hospital. RESULTS: The estimated mean difference (95% confidence interval) between the intervention and control hospitals was -0.3 (-0.9 to 0.3) days in the time to recovery and 0.2 (-0.8 to 1.3) days in the total length of hospital stay. The mean (± standard deviation) absolute rate of implemented perioperative care elements per hospital was 28.9 ± 14.9% in the control, versus 29.3 ± 11.1% in the intervention group (p = 0.934). CONCLUSION: Initial implementation effects seem to be restricted to the participating teams and do not automatically spread to other surgical teams in the same hospital.
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Procedimientos Quirúrgicos Electivos , Procedimientos Quirúrgicos Ginecológicos , Atención Perioperativa/métodos , Recuperación de la Función , Anciano , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Calidad de la Atención de Salud , Estudios RetrospectivosRESUMEN
BACKGROUND: The scope of implementation research is often restricted to the analysis of organizations that participate voluntarily in implementation interventions. The recruitment of participants for a quality improvement collaborative increases awareness of the specific innovation. The objective of this multiphase observational study was to identify differences between organizations that participated in a large-scale implementation project aiming to improve perioperative care, functional recovery, and length of hospital stay after gynecologic surgery and organizations that did not participate. A secondary objective was to explore how perioperative practice changed among nonparticipants. METHODS: Of the seven gynecology departments of nonparticipating Dutch hospitals, five agreed to participate in a retrospective analysis. Baseline data of participating hospitals' (N = 19) characteristics, time to functional recovery, and length of hospital stay were compared. Outcome measures for the subsequent pre-post awareness study in the five nonparticipating hospitals were: (1) overall adherence to predefined evidence-based perioperative elements; and (2) change in functional recovery and length of hospital stay. Multivariable regression models, adjusted for baseline characteristics, were used for analysis. RESULTS: In retrospect, nonparticipating and participating hospitals did not differ in baseline characteristics, functional recovery, and length of hospital stay. In three of the five nonparticipating hospitals, adherence to the selected evidence-based perioperative elements increased significantly after awareness of the trial (overall mean difference 9.7%, 95% CI 6.9 to 12.5%, p < 0.001). Linear regression models revealed no statistically significant or clinically relevant differences in time to functional recovery (mean difference - 0.2 days, 95% CI -0.7 to 0.2, p = 0.319) or length of hospital stay (mean difference - 0.4 days, 95% CI -1.3 to 0.5, p = 0.419) in the nonparticipating hospitals. None of these hospitals managed to reduce time to functional recovery or length of hospital stay significantly. CONCLUSIONS: No differences in perioperative outcomes between the nonparticipating and participating hospitals were identified at baseline. Despite the statistically significant improvement in overall evidence-based perioperative care, the awareness raised by recruitment activities alone was not enough to reduce time to functional recovery and length of hospital stay in nonparticipating hospitals. Insight into the trends of nonparticipants is valuable to existing implementation effectiveness research.
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Procedimientos Quirúrgicos Ginecológicos/normas , Atención Perioperativa/normas , Mejoramiento de la Calidad/organización & administración , Anciano , Femenino , Humanos , Persona de Mediana Edad , Innovación Organizacional , Atención Perioperativa/métodos , Recuperación de la Función , Estudios RetrospectivosRESUMEN
OBJECTIVES: To analyze how well untrained examiners - without experience in the use of International Ovarian Tumor Analysis (IOTA) terminology or simple ultrasound-based rules (simple rules) - are able to apply IOTA terminology and simple rules and to assess the level of agreement between non-experts and an expert. METHODS: This prospective multicenter cohort study enrolled women with ovarian masses. Ultrasound was performed by non-expert examiners and an expert. Ultrasound features were recorded using IOTA nomenclature, and used for classifying the mass by simple rules. Interobserver agreement was evaluated with Fleiss' kappa and percentage agreement between observers. RESULTS: 50 consecutive women were included. We observed 46 discrepancies in the description of ovarian masses when non-experts utilized IOTA terminology. Tumor type was misclassified often (nâ=â22), resulting in poor interobserver agreement between the non-experts and the expert (kappaâ=â0.39, 95â%-CI 0.244â-â0.529, percentage of agreementâ=â52.0â%). Misinterpretation of simple rules by non-experts was observed 57 times, resulting in an erroneous diagnosis in 15 patients (30â%). The agreement for classifying the mass as benign, malignant or inconclusive by simple rules was only moderate between the non-experts and the expert (kappaâ=â0.50, 95â%-CI 0.300â-â0.704, percentage of agreementâ=â70.0â%). The level of agreement for all 10 simple rules features varied greatly (kappa index range: -0.08â-â0.74, percentage of agreement 66â-â94â%). CONCLUSION: Although simple rules are useful to distinguish benign from malignant adnexal masses, they are not that simple for untrained examiners. Training with both IOTA terminology and simple rules is necessary before simple rules can be introduced into guidelines and daily clinical practice.
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Enfermedades de los Anexos , Neoplasias Ováricas , Terminología como Asunto , Enfermedades de los Anexos/diagnóstico por imagen , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Ováricas/diagnóstico por imagen , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: Female renal transplant recipients (RTRs) have increased risk for developing human papillomavirus (HPV)-related (pre)malignancies of the lower genital tract. Annual cervical screening is advised for RTRs, but the participation rate is low. The aim of this study is to investigate whether HPV self-sampling is suitable for gynecological screening of RTRs to increase participation rate. METHODS: A large cohort of 253 RTRs was investigated for the prevalence of HPV. All participants received a device for a cervicovaginal self-sample. Questionnaires were sent to assess the experience with this device. High-risk (hrHPV) presence was determined with the SPF10-LiPA25 system and GP5+/6+ PCR. HrHPV-positive patients underwent gynecological examination. RESULTS: More than 90% of the patients rated their experience with the self-sample device as good to excellent, and 77% preferred self-sampling over a physician taken sample. Approximately thirty-five of 217 women tested hrHPV positive with SPF10- LiPA25, and 22 tested positive with the GP5+/6+ PCR. Eleven hrHPV-positive patients had clinically relevant gynecological abnormalities, and they all tested positive with GP5+/6+ PCR. CONCLUSIONS: Self-sampling is clinically applicable in a gynecological screening and is preferred by female RTRs. Therefore, self-sampling could be implemented with the aim to increase the participation rate of female RTRs in yearly gynecological screening.
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Detección Precoz del Cáncer/métodos , Trasplante de Riñón , Infecciones por Papillomavirus/diagnóstico , Autoexamen/métodos , Manejo de Especímenes/métodos , Receptores de Trasplantes , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Aceptación de la Atención de Salud , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis. METHODS: We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC. RESULTS: BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HRmult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HRmult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HRmult 1.15; 95% CI 0.84-1.57) and OCSS (HRmult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HRmult 1.99; 95% CI 1.21-3.31). CONCLUSIONS: Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Mutación/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/genética , Pronóstico , Adulto JovenRESUMEN
INTRODUCTION: Enhanced recovery pathways have been widely accepted and implemented for different types of surgery. Their overall effect in abdominal gynecologic surgery is still underdetermined. A systematic review and meta-analysis were performed to provide an overview of current evidence and to examine their effect on postoperative outcomes in women undergoing open gynecologic surgery. MATERIAL AND METHODS: Searches were conducted using Embase, Medline, CINAHL, and the Cochrane Library up to 27 June 2014. Reference lists were screened to identify additional studies. Studies were included if at least four individual items of an enhanced recovery pathway were described. Outcomes included length of hospital stay, complication rates, readmissions, and mortality. Quantitative analysis was limited to comparative studies. Effect sizes were presented as relative risks or as mean differences (MD) with 95% confidence intervals (CI). RESULTS: Thirty-one records, involving 16 observational studies, were included. Diversity in reported elements within studies was observed. Preoperative education, early oral intake, and early mobilization were included in all pathways. Five studies, with a high risk of bias, were eligible for quantitative analysis. Enhanced recovery pathways reduced primary (MD -1.57 days, 95% CI CI -2.94 to -0.20) and total (MD -3.05 days, 95% CI -4.87 to -1.23) length of hospital stay compared with traditional perioperative care, without an increase in complications, mortality or readmission rates. CONCLUSION: The available evidence based on a broad range of non-randomized studies at high risk of bias suggests that enhanced recovery pathways may reduce length of postoperative hospital stay in abdominal gynecologic surgery.
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Abdomen/cirugía , Procedimientos Quirúrgicos Ginecológicos , Atención Perioperativa , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Readmisión del Paciente , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: Estimating the risk of malignancy is essential in the management of adnexal masses. An accurate differential diagnosis between benign and malignant masses will reduce morbidity and costs due to unnecessary operations, and will improve referral to a gynecologic oncologist for specialized cancer care, which improves outcome and overall survival. The Risk of Malignancy Index is currently the most commonly used method in clinical practice, but has a relatively low diagnostic accuracy (sensitivity 75-80% and specificity 85-90%). Recent reports show that other methods, such as simple ultrasound-based rules, subjective assessment and (Diffusion Weighted) Magnetic Resonance Imaging might be superior to the RMI in the pre-operative differentiation of adnexal masses. METHODS/DESIGN: A prospective multicenter cohort study will be performed in the south of The Netherlands. A total of 270 women diagnosed with at least one pelvic mass that is suspected to be of ovarian origin who will undergo surgery, will be enrolled. We will apply the Risk of Malignancy Index with a cut-off value of 200 and a two-step triage test consisting of simple ultrasound-based rules supplemented -if necessary- with either subjective assessment by an expert sonographer or Magnetic Resonance Imaging with diffusion weighted sequences, to characterize the adnexal masses. The histological diagnosis will be the reference standard. Diagnostic performances will be expressed as sensitivity, specificity, positive and negative predictive values and likelihood ratios. DISCUSSION: We hypothesize that this two-step triage test, including the simple ultrasound-based rules, will have better diagnostic accuracy than the Risk of Malignancy Index and therefore will improve the management of women with adnexal masses. Furthermore, we expect this two-step test to be more cost-effective. If the hypothesis is confirmed, the results of this study could have major effects on current guidelines and implementation of the triage test in daily clinical practice could be a possibility. TRIAL REGISTRATION: ClinicalTrials.gov: registration number NCT02218502.
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Análisis Costo-Beneficio , Neoplasias Ováricas , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Países Bajos , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/economía , Neoplasias Ováricas/patología , Estudios Prospectivos , Proyectos de Investigación , Riesgo , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80-96% but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated. METHODS: A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40-45 (BRCA1) or 45-50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed. DISCUSSION: The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02321228 ).