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1.
Lancet ; 403(10430): 984-996, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38458217

RESUMEN

Globally, 9 million women are diagnosed with cancer each year. Breast cancer is the most commonly diagnosed cancer worldwide, followed by colorectal cancer in high-income countries and cervical cancer in low-income countries. Survival from cancer is improving and more women are experiencing long-term effects of cancer treatment, such as premature ovarian insufficiency or early menopause. Managing menopausal symptoms after cancer can be challenging, and more severe than at natural menopause. Menopausal symptoms can extend beyond hot flushes and night sweats (vasomotor symptoms). Treatment-induced symptoms might include sexual dysfunction and impairment of sleep, mood, and quality of life. In the long term, premature ovarian insufficiency might increase the risk of chronic conditions such as osteoporosis and cardiovascular disease. Diagnosing menopause after cancer can be challenging as menopausal symptoms can overlap with other common symptoms in patients with cancer, such as fatigue and sexual dysfunction. Menopausal hormone therapy is an effective treatment for vasomotor symptoms and seems to be safe for many patients with cancer. When hormone therapy is contraindicated or avoided, emerging evidence supports the efficacy of non-pharmacological and non-hormonal treatments, although most evidence is based on women older than 50 years with breast cancer. Vaginal oestrogen seems safe for most patients with genitourinary symptoms, but there are few non-hormonal options. Many patients have inadequate centralised care for managing menopausal symptoms after cancer treatment, and more information is needed about cost-effective and patient-focused models of care for this growing population.


Asunto(s)
Neoplasias de la Mama , Calidad de Vida , Femenino , Humanos , Menopausia , Sofocos/terapia , Sofocos/tratamiento farmacológico , Terapia de Reemplazo de Hormonas , Neoplasias de la Mama/tratamiento farmacológico
2.
Ann Surg Oncol ; 31(1): 460-472, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37875740

RESUMEN

PURPOSE: The purpose of this paper is to report on changes in overall survival, progression-free survival, and complete cytoreduction rates in the 5-year period after the implementation of a multidisciplinary surgical team (MDT). METHODS: Two cohorts were used. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients from January 2017 to September 2021. RESULTS: This study included 146 patients in cohort A (2006-2015) and 174 patients in cohort B (2017-2021) with FIGO stage III/IV ovarian cancer. Median follow-up in cohort A was 60 months and 48 months in cohort B. The rate of primary cytoreductive surgery increased from 38% (55/146) in cohort A to 46.5% (81/174) in cohort B. Complete macroscopic resection increased from 58.9% (86/146) in cohort A to 78.7% (137/174) in cohort B (p < 0.001). At 3 years, 75% (109/144) patients had disease progression in cohort A compared with 48.8% (85/174) in cohort B (log-rank, p < 0.001). Also at 3 years, 64.5% (93/144) of patients had died in cohort A compared with 24% (42/174) of cohort B (log-rank, p < 0.001). Cox multivariate analysis demonstrated that MDT input, residual disease, and age were independent predictors of overall (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.203-0.437, p < 0.001) and progression-free survival (HR 0.31, 95% CI 0.21-0.43, p < 0.001). Major morbidity remained stable throughout both study periods (2006-2021). CONCLUSIONS: Our data demonstrate that the implementation of multidisciplinary-team, intraoperative approach allowed for a change in surgical philosophy and has resulted in a significant improvement in overall survival, progression-free survival, and complete resection rates.


Asunto(s)
Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Estudios Retrospectivos , Carcinoma Epitelial de Ovario/cirugía , Modelos de Riesgos Proporcionales , Análisis Multivariante , Procedimientos Quirúrgicos de Citorreducción/métodos , Estadificación de Neoplasias
3.
Int J Cancer ; 153(1): 120-132, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-36883413

RESUMEN

Resistance to platinum-based chemotherapy is the major cause of death from high-grade serous ovarian cancer (HGSOC). We hypothesise that detection of specific DNA methylation changes may predict platinum resistance in HGSOC. Using a publicly available "discovery" dataset we examined epigenomic and transcriptomic alterations between primary platinum-sensitive (n = 32) and recurrent acquired drug resistant HGSOC (n = 28) and identified several genes involved in immune and chemoresistance-related pathways. Validation via high-resolution melt analysis of these findings, in cell lines and HGSOC tumours, demonstrated the most consistent changes were observed in three of the genes: APOBEC3A, NKAPL and PDCD1. Plasma samples from an independent HGSOC cohort (n = 17) were analysed using droplet digital PCR. Hypermethylation of NKAPL was detected in 46% and hypomethylation of APOBEC3A in 69% of plasma samples taken from women with relapsed HGSOC (n = 13), with no alterations identified in disease-free patients (n = 4). Following these results, and using a CRISPR-Cas9 approach, we were also able to demonstrate that in vitro NKAPL promoter demethylation increased platinum sensitivity by 15%. Overall, this study demonstrates the importance of aberrant methylation, especially of the NKAPL gene, in acquired platinum resistance in HGSOC.


Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Platino (Metal)/farmacología , Platino (Metal)/uso terapéutico , Resistencia a Antineoplásicos/genética , Epigenómica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Carcinoma Epitelial de Ovario , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología
4.
BJOG ; 130(12): 1437-1450, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37132126

RESUMEN

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.


Asunto(s)
Neoplasias Ováricas , Salpingooforectomía , Femenino , Humanos , Adulto , Persona de Mediana Edad , Calidad de Vida , Consenso , Premenopausia , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/cirugía , Ovariectomía , Predisposición Genética a la Enfermedad
5.
Gynecol Oncol ; 167(2): 314-322, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36163055

RESUMEN

OBJECTIVE: Investigate the clinical and functional implications of elevated CRABP2 expression in endometrial cancer (EC) patients. METHODS: Patients were stratified into high and low CRABP2 expression groups using a decision tree classifier. Univariate and multivariate statistical analyses determined the prognostic and clinicopathological consequences of increased CRABP2 expression. A CRABP2 gene signature was generated using differential expression analysis, and analyzed using network-based approaches. The findings were validated in The Clinical Proteomic Tumor Analysis Consortium (CPTAC), a newly generated cohort of 120 endometrial tissues, and The Cancer Dependency Map (DepMap). RESULTS: 60 (11%) patients in TCGA had high CRABP2 expression, whilst 468 (89%) had low expression. High expression was associated with serous EC, reduced overall survival, advanced stage and grade. Downstream retinoic acid receptors (RARG and RARA) were correlated with CRABP2 expression and were associated with worse prognosis in serous EC. The CRABP2 gene signature was enriched for Polycomb target gene sets, and was regulated by ELP3 and BMP7. BMP7 expression was increased in the CRABP2-high group, was associated with worse prognosis, and CRISPR-Cas9 screens revealed correlations in its cell-fitness score with CRABP2 following gene knockout. The opposite was true for ELP3, suggesting opposing effects from both master regulators. CONCLUSIONS: CRABP2 expression is associated with poor prognosis and advanced EC. The expression of RARA and RARG correlates with CRABP2 and are associated with worse prognosis in advanced histological subtypes. Polycomb target gene sets and two master regulators, ELP3 and BMP7, were identified as functionally relevant mechanisms driving aberrant CRABP2 expression.


Asunto(s)
Neoplasias Endometriales , Receptores de Ácido Retinoico , Femenino , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Regulación Neoplásica de la Expresión Génica , Pronóstico , Proteómica , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo
6.
BMC Pregnancy Childbirth ; 22(1): 397, 2022 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-35538441

RESUMEN

BACKGROUND: Placenta Accreta Spectrum is associated with significant clinical maternal morbidity and mortality, which has been extensively described in the literature. However, there is a dearth of research on the lived experiences of pregnant people and their support partners. The aim of this study is to describe living beyond a pregnancy and birth complicated by PAS for up to four years postpartum. Participants experiences inform the development of an integrated care pathway of family centered support interventions. METHODS: An Interpretative Phenomenological Analysis approach was applied to collect data through virtual interviews over a 3-month period from February to April 2021. Twenty-nine participants shared their stories; six people with a history of PAS and their support partners were interviewed together (n = 12 participants), six were interviewed separately (n = 12 participants), and five were interviewed without their partner. Pregnant people were eligible for inclusion if they had a diagnosis of PAS within the previous 5 years. This paper focuses on the postnatal period, with data from the antenatal and intrapartum periods described separately. RESULTS: One superordinate theme "Living beyond PAS" emerged from interviews, with 6 subordinate themes as follows; "Living with a different body", "The impact on relationships", "Coping strategies", "Post-traumatic growth", "Challenges with normal care" and recommendations for "What needs to change". These themes informed the development of an integrated care pathway for pregnant people and their support partners to support them from diagnosis up to one year following the birth. CONCLUSION: Parents described the challenges of the postnatal period in terms of the physical and emotional impact, and how some were able to make positive life changes in the aftermath of a traumatic event. An integrated care pathway of simple supportive interventions, based on participant recommendations, delivered as part of specialist multidisciplinary team care may assist pregnant people and their support partners in alleviating some of these challenges.


Asunto(s)
Prestación Integrada de Atención de Salud , Placenta Accreta , Femenino , Humanos , Padres , Parto , Placenta Accreta/terapia , Periodo Posparto , Embarazo
7.
Ann Surg Oncol ; 28(8): 4553-4560, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33423175

RESUMEN

BACKGROUND: Surgical resection remains the cornerstone of ovarian cancer management. In 2017, the authors implemented a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper gastrointestinal (GI) surgeons to increase gross macroscopic resection rates. This report aims to describe changes in complete cytoreduction rates and morbidity after the implementation of a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper GI surgeons in a tertiary gynecologic oncology unit. METHODS: The study used two cohorts. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients initiated in 2017. A multidisciplinary approach to preoperative medical optimization, intraoperative management, and postoperative care was implemented in 2017. The patients in cohort B with upper abdominal disease were offered primary cytoreduction with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Before 2017, the patients with upper abdominal disease received neoadjuvant chemotherapy (cohort A). RESULTS: This study included 146 patients in cohort A (2006-2015) and 93 patients in cohort B (2017-2019) with stages 3 or 4 ovarian cancer. The overall complete macroscopic resection rate (CC0) increased from 58.9 in cohort A to 67.7% in cohort B. The rate of primary cytoreductive surgery (CRS) increased from 38 (55/146) in cohort A to 42% (39/93) in cohort B. The CC0 rate for the patients who underwent primary CRS increased from 49 in cohort A to 77% in cohort B. Major morbidity remained stable throughout both study periods (2006-2019). CONCLUSIONS: The study data demonstrate that implementation of a multidisciplinary team intraoperative approach and a meticulous approach to preoperative optimization resulted in significantly improved complete resection rates, particularly for women offered primary CRS.


Asunto(s)
Neoplasias de los Genitales Femeninos , Hipertermia Inducida , Neoplasias Ováricas , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Femenino , Neoplasias de los Genitales Femeninos/cirugía , Humanos , Neoplasias Ováricas/cirugía , Estudios Retrospectivos , Tasa de Supervivencia
8.
Aust N Z J Obstet Gynaecol ; 61(5): 708-714, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33763885

RESUMEN

BACKGROUND AND AIMS: Little is known about the impact of Placenta Accreta Spectrum (PAS) on quality of life (QoL). This study aims to explore QoL and sexual function after a pregnancy complicated by PAS. METHODS: Women who experienced a pregnancy complicated by PAS were invited to complete an online survey. Two validated surveys were completed: Short Form 36 (SF-36) and Female Sexual Function Index (FSFI). The mean scores were calculated and were compared between women by pregnancy outcomes. Continuous variables were presented as mean (standard deviation (SD)) and were compared to assess for significance between groups using independent t-test and one-way analysis of variance. Categorical variables were compared using χ2 test. RESULTS: A total of 142 women responded to the survey. For the SF-36, physical health was significantly higher for women at 24-36 months postpartum compared to those from 0-6 months postpartum for physical functioning (mean difference 21.9 (95% confidence interval (CI) 10.2, 33.5), role limitation due to physical function (mean difference 32.1 (95% CI 9.4, 54.7)) and pain (mean difference 15.5 (95% CI 3.4, 30.9)). For the mental health domains, only vitality improved at 24-36 months compared to the first six months postpartum (mean difference 12.8 (95% CI 0.2, 25.5)). The mean FSFI score was 24.8 (±5.8), lower than the critical score of 26.5 indicating sexual dysfunction, and 56.8% (n = 75), scored less than 26.5. CONCLUSION: Women after a pregnancy complicated by PAS had high scores on the physical health domains of SF-36. The mental health scores were lower for all women regardless of time since birth.


Asunto(s)
Placenta Accreta , Disfunciones Sexuales Fisiológicas , Femenino , Humanos , Periodo Posparto , Embarazo , Calidad de Vida , Disfunciones Sexuales Fisiológicas/etiología , Encuestas y Cuestionarios
9.
Ann Surg Oncol ; 27(9): 3553-3564, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32221737

RESUMEN

BACKGROUND: Sarcopenia is defined as a progressive loss of skeletal muscle mass, strength and physical performance. Myosteatosis is an increase of intra- and intermuscular fat and can be measured radiologically by muscle attenuation. The study aim was to perform a systematic review and meta-analysis on the prognostic potential of sarcopenia and low muscle attenuation in relation to 3-year survival rates (3YSR) and 5YSR in epithelial ovarian cancer (EOC). METHODS: A systematic literature search was conducted using the databases Ovid Medline, EMBASE, and Scopus, using PRISMA guidelines, from inception to 10th of May 2019. Studies evaluated the prognostic potential of sarcopenia and low muscle attenuation on 3YSR and 5YSR in EOC. Quality assessment of included studies was performed using the Methodological Index for Non-Randomised Studies criteria. RESULTS: A comprehensive search of databases resulted in the identification of 2194 studies, resulting in 1695 citations meeting the inclusion criteria. Six studies were included for systematic review. Sarcopenia was not significantly associated with improved 3YSR (OR 1.7, 95% CI 0.8-3.5, p = 0.15) or 5YSR (OR 1.8, 95% CI 1.0-3.2, p = 0.07) in meta-analysis. Normal muscle attenuation was associated with a favourable 3YSR (OR 3.0, 95% CI 2.0-4.5, p < 0.001) and 5YSR (OR 2.3, 95% CI 1.6-3.4, p < 0.001) compared to low muscle attenuation. CONCLUSION: Our meta-analysis indicated normal muscle attenuation was significantly associated with improved 3YSR and 5YSR in patients with EOC. Sarcopenia was not significantly associated with 3YSR or 5YSR in patients with EOC.


Asunto(s)
Carcinoma Epitelial de Ovario , Neoplasias Ováricas , Sarcopenia , Tejido Adiposo/diagnóstico por imagen , Carcinoma Epitelial de Ovario/complicaciones , Carcinoma Epitelial de Ovario/mortalidad , Femenino , Humanos , Músculo Esquelético/diagnóstico por imagen , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/mortalidad , Pronóstico , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Sarcopenia/mortalidad , Análisis de Supervivencia
10.
Int J Gynecol Cancer ; 30(11): 1811-1823, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32381512

RESUMEN

OBJECTIVES: This review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular markers to reproducibly identify 'low-risk' cancers which may represent the best candidates for progestin therapy. We also discuss constraints in current approaches to progestin treatment of low-grade endometrial cancer and perform a systematic review of predictive biomarkers. METHODS: PubMed, ClinicalTrials.gov, and Cochrane Library were searched for studies reporting pre-treatment biomarkers associated with outcome in women with low-grade endometrial cancer or endometrial hyperplasia with an intact uterus who received progestin treatment. Studies of fewer than 50 women were excluded. The study protocol was registered in PROSPERO (ID 152374). A descriptive synthesis of pre-treatment predictive biomarkers reported in the included studies was conducted. RESULTS: Of 1908 records reviewed, 19 studies were included. Clinical features such as age or body mass index cannot predict progestin response. Lesions defined as 'low-risk' by FIGO criteria (stage 1A, grade 1) can respond well; however, the reproducibility and prognostic ability of the current histopathological classification system is suboptimal. Molecular markers can be reproducibly assessed, have been validated as prognostic biomarkers, and may inform patient selection for progestin treatment. DNA polymerase epsilon (POLE)-ultramutated tumors and a subset of p53 wild-type or DNA mismatch repair (MMR)-deficient tumors with 'low-risk' features (eg, progesterone and estrogen receptor-positive) may have improved response rates, though this needs to be validated. DISCUSSION: Molecular markers can identify cases which may be candidates for progestin treatment. More work is needed to validate these biomarkers and potentially identify new ones. Predictive biomarkers are anticipated to inform future research into progestin treatment of low-grade endometrial cancer and ultimately improve patient outcomes.


Asunto(s)
Hiperplasia Endometrial/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Progestinas/administración & dosificación , Biomarcadores de Tumor , Hiperplasia Endometrial/genética , Neoplasias Endometriales/clasificación , Neoplasias Endometriales/genética , Femenino , Humanos , Recurrencia Local de Neoplasia/prevención & control , Factores de Riesgo
11.
Proc Natl Acad Sci U S A ; 114(27): 7077-7082, 2017 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-28630300

RESUMEN

G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse factor in tumor growth and metastasis, the role of G9a in regulating gene expression in hypoxia has not been described extensively. Here, we show that G9a protein stability is increased in hypoxia via reduced proline hydroxylation and, hence, inefficient degradation by the proteasome. This inefficiency leads to an increase in H3K9me2 at its target promoters. Blocking the methyltransferase activity of G9a inhibited cellular proliferation and migration in vitro and tumor growth in vivo. Furthermore, an increased level of G9a is a crucial factor in mediating the hypoxic response by down-regulating the expression of specific genes, including ARNTL, CEACAM7, GATA2, HHEX, KLRG1, and OGN This down-regulation can be rescued by a small molecule inhibitor of G9a. Based on the hypothesis that the changes in gene expression would influence patient outcomes, we have developed a prognostic G9a-suppressed gene signature that can stratify breast cancer patients. Together, our findings provide an insight into the role G9a plays as an epigenetic mediator of hypoxic response, which can be used as a diagnostic marker, and proposes G9a as a therapeutic target for solid cancers.


Asunto(s)
Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Hipoxia/genética , Animales , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular , Supervivencia sin Enfermedad , Epigénesis Genética , Femenino , Perfilación de la Expresión Génica , Humanos , Células MCF-7 , Neoplasias Mamarias Experimentales/genética , Ratones , Ratones Endogámicos C57BL , Pronóstico , Prolina/química , Procesamiento Proteico-Postraduccional , ARN Interferente Pequeño/metabolismo , Recurrencia , Microambiente Tumoral
12.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-32069845

RESUMEN

Obesity is a major public health concern worldwide. The increased risk of certain types of cancer is now an established deleterious consequence of obesity, although the molecular mechanisms of this are not completely understood. In this review, we aim to explore the links between MAPK signalling and obesity-related cancer. We focus mostly on p38 and JNK MAPK, as the role of ERK remains unclear. These links are seen through the implication of MAPK in obesity-related immune paralysis as well as through effects on the endoplasmic reticulum stress response and activation of aromatase. By way of example, we highlight areas of interest and possibilities for future research in endometrioid endometrial cancer and hepatocellular carcinoma associated with non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and MAPK.


Asunto(s)
Proteínas Quinasas JNK Activadas por Mitógenos/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Estrés del Retículo Endoplásmico/genética , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/complicaciones , Obesidad/patología
13.
Gynecol Oncol ; 154(3): 622-630, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31349996

RESUMEN

Aim The aim of this meta-analysis is to review the morbidity and mortality associated with primary cytoreductive surgery (PCS) compared to neoadjuvant chemotherapy and interval cytoreductive surgery (NACT + ICS) for advanced ovarian cancer. METHODS: A literature search was performed for publications reporting morbidity and mortality in patients undergoing PCS compared to NACT + ICS. Databases searched were Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov and Embase. Two independent reviewers applied inclusion and exclusion criteria to select included papers, with differences agreed by consensus. A total of 1341 citations were reviewed; 17 studies comprising 3759 patients were selected for the analysis. The literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Patients in the PCS group were significantly more likely to have a Clavien-Dindo grade ≥ 3 morbidity with an overall rate of 21.2% compared to 8.8% (95%CI 1.9-4.0, p < 0.0001) and were more likely to die within 30 days of surgery (OR 6.1, 95% CI 2.1-17.6, p = 0.0008). Patients who underwent NACT + ICS had significantly shorter procedural times (MD -35 min, p = 0.01), lost less blood intraoperatively (MD-382 ml, p < 0.001) and had an average admission 5.0 days shorter (MD -5.0 days, 95% CI -8.1 to -1.9 days, p = 0.002) than those undergoing PCS. While NACT was associated with significantly increased optimal and complete cytoreduction rates (OR 1.9, 95% CI 1.3-2.9, p = 0.001, and OR 2.2, 95% CI 1.5-3.3, p = 0.0001 respectively), this did not confer any additional survival benefit (OR 1.0, p = 0.76). CONCLUSION: NACT is associated with less morbidity and mortality and improved complete cytoreduction compared to PCS, with no survival benefit. Hence NACT is an acceptable alternative in selected patients in particular with medical co-morbidities or a high tumour burden.


Asunto(s)
Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Morbilidad , Terapia Neoadyuvante , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
Int J Gynecol Cancer ; 28(6): 1073-1076, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29664842

RESUMEN

INTRODUCTION: Multidetector computed tomography (MDCT) is routinely used in the surveillance of epithelial ovarian cancer. The aim of this study was to determine the incidence of thoracic findings on routine MDCT surveillance imaging in patients with ovarian carcinoma. MATERIALS AND METHODS: Retrospective evaluation of 100 MDCT studies of patients with a diagnosis of epithelial ovarian cancer was performed at a university teaching hospital. The cross-sectional studies were reviewed by a consultant radiologist with subspeciality training in cross-sectional imaging. RESULTS: Intrathoracic findings were identified in 35% of patients. Pleural effusions were identified in 40%, pulmonary nodules in 37%, mediastinal adenopathy in 17%, and thyroid nodules in 6% of patients. Thirty-five (35%) patients were found to have thoracic findings on computed tomography. Pleural effusions developed in 14 (40%) of these patients. Small lung nodules (<1 cm) were present in 13 (37%) patients. Mediastinal lymphadenopathy was seen in 6 (17%) patients. Two patients (6%) had thyroid nodules of unknown significance. Pleural effusions and small lung nodules were present at a similar level to that of the general population. CONCLUSIONS: This retrospective study supports the imaging recommendations of the European Society of Urogenital Radiology that MDCT protocols for the initial staging and evaluation of recurrent disease in epithelial ovarian carcinoma require only inclusion of the lung bases to the inguinal region reducing exposure to ionizing radiation, alleviating patient anxiety, and offering a cost-benefit to hospitals.


Asunto(s)
Carcinoma Epitelial de Ovario/diagnóstico por imagen , Enfermedades Torácicas/diagnóstico por imagen , Tórax/diagnóstico por imagen , Femenino , Humanos , Hallazgos Incidentales , Neoplasias Pulmonares/diagnóstico por imagen , Linfadenopatía/diagnóstico por imagen , Enfermedades del Mediastino/diagnóstico por imagen , Derrame Pleural Maligno/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
16.
Br J Cancer ; 114(4): 417-26, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26882065

RESUMEN

BACKGROUND: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. METHODS: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis. RESULTS: Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts. CONCLUSIONS: CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer.


Asunto(s)
Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Cistadenocarcinoma Seroso/patología , Proteínas de Neoplasias/metabolismo , Neoplasias Ováricas/patología , Animales , Antígenos CD/genética , Antígenos de Neoplasias , Biomarcadores de Tumor/metabolismo , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Cistadenocarcinoma Seroso/metabolismo , Modelos Animales de Enfermedad , Femenino , Xenoinjertos , Humanos , Ratones , Clasificación del Tumor , Proteínas de Neoplasias/genética , Neoplasias Ováricas/metabolismo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Análisis de Supervivencia
19.
BMC Cancer ; 15: 33, 2015 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-25655024

RESUMEN

BACKGROUND: The purpose of this study was to evaluate serum HE4 as a biomarker to detect recurrent disease during follow-up of patients with endometrial adenocarcinoma (EAC). METHODS: We performed a retrospective analysis of 98 EAC patients treated at Innsbruck Medical University, between 1999 and 2009. Twenty-six patients developed recurrent disease. Median follow-up was 5 years. Serum HE4 and CA125 levels were analyzed using the ARCHITECT assay (Abbott, Wiesbaden, Germany) pre-operatively (baseline), post-operative (interval) and after histological confirmation of recurrent disease or when patients returned for clinical review with no evidence of recurrent disease (recurrence/final)). Receiver operator curves (ROC), Spearman rank correlation coefficient, chi-squared and Mann-Whitney tests were used for statistical analysis. RESULTS: HE4 levels decreased after initial treatment (p = 0.001) and increased again at recurrence (p = 0.002). HE4 was elevated (>70 pmol/L) in 21 of 26 (81%) and CA125 was elevated (>35 U/ml) in 12 of 26 (46%) patients at recurrence. In endometrioid histology (n = 69) serum HE4 measured during follow up (Area under the curve (AUC) = 0.87, 95%CI 0.79-0.95) was a better indicator of recurrence than CA125 (AUC = 0.67, 95%CI 0.52-0.83). A HE4 level of 70 pmol/L was associated with a sensitivity of 84%, a specificity of 74% and a negative predictive value of 93% when assessing for recurrent endometrioid EAC. CONCLUSION: This is a preliminary description of HE4 serum levels measured during routine follow up of EAC patients. Serum HE4 measured during clinical follow-up may identify recurrent disease particularly in patients with endometrioid histology. Further prospective validation of HE4 is warranted.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Endometriales/sangre , Neoplasias Endometriales/patología , Proteínas , Adulto , Anciano , Anciano de 80 o más Años , Antígeno Ca-125/sangre , Neoplasias Endometriales/terapia , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Curva ROC , Estudios Retrospectivos , Resultado del Tratamiento , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP
20.
Acta Obstet Gynecol Scand ; 94(12): 1380-6, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26344420

RESUMEN

INTRODUCTION: Abnormally invasive placenta is a major cause of maternal morbidity and mortality. The aim of this study was to assess the effectiveness of a standardized operative approach performed by gynecological oncologists in the surgical management of abnormally invasive placenta. MATERIALS AND METHODS: We performed a retrospective analysis of all cases of morbid placental adherence managed at the Mater Mothers' Hospitals, Brisbane, Australia between January 2000 and June 2013. A standard operative approach involving extensive retro-peritoneal and bladder dissection before delivery of the fetus, was undertaken when a gynecological oncologist was present at the start of the procedure. Main outcome measures were estimated blood loss, transfusion requirements, and maternal and neonatal morbidity. RESULTS: The study includes 98 cases of histologically confirmed abnormally invasive placenta. Median estimated blood loss for the entire cohort was 2150 mL (range 300-11 500 mL). Women were divided into three groups, (1) those who had a gynecological oncologist present at the start of the procedure (group 1; n = 43), (2) those who had a gynecological oncologist called in during the procedure (group 2; n = 23), and (3) those who had no gynecological oncologist involved (group 3; n = 32). Group 2 had a significantly higher blood loss than the other groups (p = 0.001) (median 4400 mL). Transfusion requirements were higher in groups 2 and 3 compared with group 1 (p = 0.004). Other maternal and neonatal morbidity was similar across all three groups. CONCLUSION: This study supports the early presence of a gynecological oncologist at delivery when abnormally invasive placenta is suspected and demonstrates that a "call if needed" approach is not acceptable for these complex cases.


Asunto(s)
Parto Obstétrico/métodos , Histerectomía/métodos , Obstetricia , Enfermedades Placentarias/cirugía , Adulto , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea/estadística & datos numéricos , Cesárea , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Recursos Humanos
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