RESUMO
BACKGROUND: The aim of this study was to determine attitude of Dutch midwifes, gynecologists and general practitioners (GPs) towards involvement in antenatal cervical cancer screening (CCS) in the Netherlands. METHODS: In 2021, Dutch midwives, gynecologists, and GPs were offered a single digital questionnaire assessing perceived feasibility, benefits, and harms of antenatal CCS. RESULTS: A total of 6943 Questionnaires were send and response rate was 18% (N = 1260). Of all respondents, 78% considered antenatal CCS via obstetric care providers feasible. Most respondents (85%) agreed that offering CCS in person can increase motivation to attend. Most midwives (93%) considered that women would feel less encumbered if cervical sampling would be performed by obstetric care providers, rather than by GPs. CONCLUSION: Results indicate that introduction of antenatal CCS is considered feasible by a majority of Dutch midwifes, gynecologists, and GPs. Considered benefits include improved motivation to attend and reduced test related barriers.
Assuntos
Atitude do Pessoal de Saúde , Detecção Precoce de Câncer , Cuidado Pré-Natal , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Países Baixos , Detecção Precoce de Câncer/psicologia , Adulto , Cuidado Pré-Natal/métodos , Gravidez , Inquéritos e Questionários , Pessoa de Meia-Idade , Tocologia , Clínicos Gerais/psicologiaRESUMO
OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.
Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Salpingo-Ooforectomia , Humanos , Feminino , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias das Tubas Uterinas/prevenção & controle , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/prevenção & controle , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/prevenção & controle , Adulto , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Mutação em Linhagem Germinativa , Genes BRCA2 , Proteína BRCA2/genética , Proteína BRCA1/genética , Genes BRCA1RESUMO
OBJECTIVE: A major side effect of cervical excision for high-grade cervical intraepithelial neoplasia (CIN) is premature birth. A non-invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high-grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared with surgical treatment and placebo. METHODS: Databases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr-HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist. RESULTS: Five studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod-treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03-8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59-33.27) for histological regression to ≤CIN 1. The hr-HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62-23.77). CONCLUSIONS: The histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Imiquimode/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia , Colo do Útero/patologia , PapillomaviridaeRESUMO
OBJECTIVES: To determine rates of vascular toxicity, acute kidney injury (AKI), chronic kidney disease (CKD) and survival in high-risk cervical cancer patients treated with platinum-based induction chemotherapy followed by thermoradiotherapy. METHODS: Between January 1999 and April 2017, patients with large primary tumors (>6cm) and/or para-aortic lymph node (LN) metastases >1 cm and/or para-iliac LN >2 cm were included. Patient and tumor characteristics, Common Toxicity Criteria v4.03 scores, laboratory tests and treatment data were retrieved from patient records. CT scans were reviewed for the presence of thrombo-embolic events (TEE). The study protocol was approved by the Medical Ethics Review Committee of Erasmus MC, Rotterdam (MEC2017-133). RESULTS: The 105 included patients had a mean age of 47.9 years (range 22-79) and a median follow-up time of 43 months (IQR 14-72). Median tumor size was 6.0 cm (range 2.6-11.5), 30% had a clinical FIGO stage ≥ IIIB and 42% had enlarged para-aortic LN. Cisplatin-based therapy was started in 86 patients (82%), of whom 30 (35%) switched to carboplatin and 47% of patients completed six cycles of platinum-based chemotherapy. All patients received external beam radiotherapy as planned, 98 patients (93%) underwent brachytherapy as planned or received an external boost, and 95 patients (90%) completed all five planned hyperthermia treatments. During cisplatin chemotherapy, 34 patients experienced AKI (39%). At last follow-up, 35% of patients had chronic renal toxicity (GFR 59 - 15/min/1.73 m2). At presentation, a TEE was present in 10 (10%) and another 23 (22%) patients experienced a TEE (18% venous, 4% arterial) during chemotherapy. Five-year overall survival was 58% (95% CI 47.8-68.6 SE 0.053). CONCLUSION: Achieving a five-year overall survival of 58%, platinum-based induction chemotherapy followed by thermoradiotherapy is an effective treatment for advanced-stage high-risk cervical cancer. However, treatment is accompanied by an unacceptably high prevalence of chemotherapy-associated TEE and acute kidney injury, as well as chronic kidney disease. Future studies should investigate the role of carboplatin in reducing toxicity and the effect of thromboprophylaxis in high-risk patients.
Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Neoplasias do Colo do Útero , Tromboembolia Venosa , Feminino , Humanos , Lactente , Pré-Escolar , Criança , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Quimioterapia de Indução , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Carboplatina/uso terapêutico , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
OBJECTIVE: Standard surgical treatment of advanced-stage ovarian carcinoma with electrosurgery cannot always result in complete cytoreductive surgery (CRS), especially when many small metastases are found on the mesentery and intestinal surface. We investigated whether adjuvant use of a neutral argon plasma device can help increase the complete cytoreduction rate. PATIENTS AND METHODS: 327 patients with FIGO stage IIIB-IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were randomized to either surgery with neutral argon plasma (PlasmaJet) (intervention) or without PlasmaJet (control group). The primary outcome was the percentage of complete CRS. The secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30-day morbidity, and quality of life (QoL). RESULTS: Complete CRS was achieved in 119 patients (75.8%) in the intervention group and 115 patients (67.6%) in the control group (risk difference (RD) 8.2%, 95% confidence interval (CI) -0.021 to 0.181; P = 0.131). In a per-protocol analysis excluding patients with unresectable disease, complete CRS was obtained in 85.6% in the intervention group and 71.5% in the control group (RD 14.1%, 95% CI 0.042 to 0.235; P = 0.005). Patient-reported QoL at 6 months after surgery differed between groups in favor of PlasmaJet surgery (95% CI 0.455-8.350; P = 0.029). Other secondary outcomes did not differ significantly. CONCLUSIONS: Adjuvant use of PlasmaJet during CRS for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete CRS in patients with resectable disease and higher QoL at 6 months after surgery. (Funded by ZonMw, Trial Register NL62035.078.17.) TRIAL REGISTRATION: Approved by the Medical Ethics Review Board of the Erasmus University Medical Center Rotterdam, the Netherlands, NL62035.078.17 on 20-11-2017. Recruitment started on 30-1-2018.
Assuntos
Neoplasias Ovarianas , Gases em Plasma , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Países Baixos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Qualidade de VidaRESUMO
BACKGROUND: Cervical cancer is caused by Human Papilloma viruses (HPV) and is preceded by precursor stages: Cervical Intraepithelial Neoplasia (CIN). CIN is mostly found in women in their reproductive age and treated with a Loop Electrosurgical Excision Procedure (LEEP). The recurrence or residual disease rate after treatment is up to 17%. These women have a lifelong increased risk of recurrent CIN, cervical cancer and other HPV related malignancies. Furthermore, LEEP treatments are associated with complications such as premature birth. Limited data show that prophylactic HPV vaccination at the time of LEEP reduces recurrence rates, therefore leading to a reduction in repeated surgical interventions and side effect like preterm birth. The primary study objective is to evaluate the efficacy of the nonavalent HPV vaccination in women with a CIN II-III (high-grade squamous intraepithelial lesion (HSIL) lesion who will undergo a LEEP in preventing recurrent CIN II-III after 24 months. METHODS: This study is a randomised, double blinded, placebo controlled trial in 750 patients without prior HPV vaccination or prior treatment for CIN and with histologically proven CIN II-III (independent of their hrHPV status) for whom a LEEP is planned. Included patients will be randomised to receive either three injections with nonavalent (9 HPV types) HPV vaccine or placebo injections (NaCL 0.9%) as a comparator. Treatment and follow-up will be according the current Dutch guidelines. Primary outcome is recurrence of a CIN II or CIN III lesion at 24 months. A normal PAP smear with negative hrHPV test serves as surrogate for absence of CIN. At the start and throughout the study HPV typing, quality of life and cost effectiveness will be tested. DISCUSSION: Although prophylactic HPV vaccines are highly effective, little is known about the effectivity of HPV vaccines on women with CIN. Multiple LEEP treatments are associated with complications. We would like to evaluate the efficacy of HPV vaccination in addition to LEEP treatment to prevent residual or recurrent cervical dysplasia and decrease risks of repeated surgical treatment. TRIAL REGISTRATION: Medical Ethical Committee approval number: NL66775.078.18. Affiliation: Erasmus Medical Centre. Dutch trial register: NL 7938. Date of registration 2019-08-05.
Assuntos
Eletrocirurgia/métodos , Recidiva Local de Neoplasia/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Fatores Etários , Alphapapillomavirus/imunologia , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Infecções por Papillomavirus/complicações , Tamanho da Amostra , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVES: Carriers of BRCA1 and BRCA2 mutations are at increased risk of high grade serous carcinoma and are therefore offered risk-reducing salpingo-oophorectomy (RRSO) by 40-45â¯years. Most of these carcinomas are believed to arise in the fallopian tube from serous tubal intraepithelial carcinoma (STIC). We conducted a retrospective study on the prevalence of high grade serous carcinoma and STIC in BRCA1/2 carriers presenting for RRSO, and their follow-up. METHODS: Consecutive BRCA1/2 carriers presenting for an RRSO at Erasmus MC (2000-2016) were studied. SEE-FIM pathology protocol was followed from 2010 onwards. For the cases with carcinoma and/or STIC, the histology was reviewed and immunohistochemistry (p53 & MIB-1) was performed. Next Generation Targeted Sequencing (NGTS) for TP53 mutation was used to establish clonality in 2 cases. RESULTS: Of the 527 included patients, 68% were BRCA1, 31.6% were BRCA2, and 0.4% carried both mutations. The prevalence of high grade serous carcinoma was 2.3% (12/527); 59% of these were of tubal origin. High grade serous carcinoma was more common in patients operated on after the recommended age (pâ¯=â¯0.03). Isolated STIC was present in 0.8% (4/527). Two BRCA1 carriers with isolated STIC at RRSO developed peritoneal serous carcinoma >7â¯years later. Identical TP53 mutations in the peritoneal serous carcinoma and the preceding STIC established their clonal origin. CONCLUSIONS: High grade serous carcinoma is more common in BRCA1/2 carriers presenting for RRSO after the recommended age, and is more often of tubal origin. Longer follow up of patients with STIC at RRSO should be considered.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma in Situ/epidemiologia , Cistadenocarcinoma Seroso/epidemiologia , Neoplasias das Tubas Uterinas/epidemiologia , Adulto , Idoso , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma in Situ/prevenção & controle , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/prevenção & controle , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/prevenção & controle , Tubas Uterinas/patologia , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prevalência , Procedimentos Cirúrgicos Profiláticos , Estudos Retrospectivos , Salpingo-OoforectomiaRESUMO
BACKGROUND: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be "complete" in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. METHODS: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery. DISCUSSION: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void. TRIAL REGISTRATION: Dutch Trial Register NTR6624 . Registered 18 August 2017. Medical Ethical Committee approval number: NL62035.078.17 (Medical Ethical Committee Erasmus Medical Centre Rotterdam).
Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Análise Custo-Benefício , Procedimentos Cirúrgicos de Citorredução/economia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Países Baixos , Neoplasias Ovarianas/mortalidade , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Cervical dysplasia (cervical intraepithelial neoplasia (CIN)) is caused by Human Papillomavirus (HPV) and is most common in women of reproductive age. Current treatment of moderate to severe CIN is surgical. This procedure has potential complications, such as haemorrhage, infection and preterm birth in subsequent pregnancies. Moreover, 15% of women treated for high grade CIN develop residual/recurrent CIN or cervical cancer after surgical excision. Finally, 75-100% of patients with a residual and recurrent CIN 2-3 lesion are still HPV positive. They could possibly benefit from an alternative medical treatment, which aims to eliminate HPV. The primary study objective is to evaluate the effectivity of imiquimod 5% cream compared to treatment with Large Loop Excision of the Transformation Zone (LLETZ) for recurrent/residual CIN. METHODS/DESIGN: This study is a multicentre, non-inferiority randomized single blinded study. The study population consists of female patients with histological proven residual/recurrent CIN after previous surgical treatment. Four hundred thirty-three patients will be included in the Netherlands. The first 35 patients will be included in a pilot study to prove non-futility. Included patients will be randomized to receive either 5% imiquimod cream or LLETZ treatment. Imiquimod will be inserted three times a week intravaginally for a period of 16 weeks using a vaginal applicator. Ten weeks after the end of imiquimod treatment a biopsy will be taken for treatment response. In case of progressive or stable disease a LLETZ will be performed. At 12 and 24 months after the start of treatment cytology will be taken for follow up. The LLETZ group will be treated according to the current guidelines. Throughout the study, HPV typing and quality of life will be tested. DISCUSSION: Repeated LLETZ in women with residual/recurrent CIN lesions has complications. We would like to possibly offer alternative treatment in a selected group to avoid these risks. Moreover, we monitor treatment efficacy, side effects and long-term recurrence rates. TRIAL REGISTRATION: Medical Ethical Committee approval number: NL 53792.078.15. Affiliation: Erasmus Medical Center. Registration number ClinicalTrials.gov : NCT02669459 , date of registration: 27th January 2016.
Assuntos
Antineoplásicos/administração & dosagem , Imiquimode/administração & dosagem , Displasia do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/cirurgia , Projetos de Pesquisa , Método Simples-Cego , Neoplasias do Colo do Útero/cirurgia , Displasia do Colo do Útero/cirurgiaRESUMO
The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.
Assuntos
Aminoquinolinas/administração & dosagem , Displasia do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Administração Tópica , Aminoquinolinas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , ImiquimodeRESUMO
BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the premalignant condition of cervical cancer. Whereas not all high grade CIN lesions progress to cervical cancer, the natural history and risk of progression of individual lesions remain unpredictable. Therefore, high-grade CIN is currently treated by surgical excision: large loop excision of the transformation zone (LLETZ). This procedure has potential complications, such as acute haemorrhage, prolonged bleeding, infection and preterm birth in subsequent pregnancies. These complications could be prevented by development of a non-invasive treatment modality, such as topical imiquimod treatment. The primary study objective is to investigate the efficacy of topical imiquimod 5% cream for the treatment of high-grade CIN and to develop a biomarker profile to predict clinical response to imiquimod treatment. Secondary study objectives are to assess treatment side-effects, disease recurrence and quality of life during and after different treatment modalities. METHODS/DESIGN: The study design is a randomized controlled trial. One hundred forty women with a histological diagnosis of high-grade CIN (CIN 2-3) will be randomized into two arms: imiquimod treatment during 16 weeks (experimental arm) or immediate LLETZ (standard care arm). Treatment efficacy will be evaluated by colposcopy with diagnostic biopsies at 20 weeks for the experimental arm. Successful imiquimod treatment is defined as regression to CIN 1 or less, successful LLETZ treatment is defined as PAP 1 after 6 months. Disease recurrence will be evaluated by cytology at 6, 12 and 24 months after treatment. Side-effects will be evaluated using a standardized report form. Quality of life will be evaluated using validated questionnaires at baseline, 20 weeks and 1 year after treatment. Biomarkers, reflecting both host and viral factors in the pathophysiology of CIN, will be tested at baseline with the aim of developing a predictive biomarker profile for the clinical response to imiquimod treatment. DISCUSSION: Treatment of high-grade CIN lesions with imiquimod in a selected patient population may diminish complications as a result of surgical intervention. More knowledge on treatment efficacy, side effects and long-term recurrence rates after treatment is necessary. TRIAL REGISTRATION: EU Clinical Trials Register EU-CTR2013-001260-34 . Registered 18 March 2013. Medical Ethical Committee approval number: NL44336.068.13 (Medical Ethical Committee Maastricht University Hospital, University of Maastricht). Affiliation: Maastricht University Hospital. Registration number ClinicalTrials.gov: NCT02329171.
Assuntos
Aminoquinolinas/administração & dosagem , Antineoplásicos/administração & dosagem , Displasia do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Imiquimode , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas Associadas a Pancreatite , Qualidade de Vida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgiaRESUMO
BACKGROUND: To assess the clinical value of peritoneal washing cytology (PWC) in women with BRCA1 or BRCA2 mutations and women from a family with hereditary breast and/or ovarian cancer (HBOC) undergoing risk-reducing salpingo-oophorectomy (RRSO) in detecting primary peritoneal cancer (PPC) or occult ovarian/fallopian tube cancer. METHODS: A retrospective study of patients with known BRCA1 or BRCA2 mutation or HBOC who underwent RRSO at the Erasmus Medical Centre, Rotterdam, The Netherlands between January 2000-2014. Patients with an elevated risk of malignancy prior to the procedure were excluded from primary analysis (elevated CA-125, an ovarian mass, abdominal pain or another gynecological malignancy). A review of the literature was conducted. RESULTS: Of the 471 patients who underwent RRSO, a total of 267 cytology samples were available for analysis. Four samples showed malignant cells, all four patients were diagnosed with ovarian and/or fallopian tube cancer at histologic examination. A fifth patient, of whom no cytology sample was obtained during RRSO, developed primary peritoneal cancer 80 months post RRSO. CONCLUSIONS: This study failed to show that cytology is of value during RRSO in detecting primary peritoneal cancer, however 36% of patients with concomitant ovarian or fallopian tube cancer had positive cytology. Therefore, the routine sampling of peritoneal washings during RRSO is not found to be useful to detect subsequent PPC.
Assuntos
Citodiagnóstico/métodos , Neoplasias das Tubas Uterinas/genética , Neoplasias Ovarianas/genética , Neoplasias Peritoneais/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Peritônio/patologia , Valor Preditivo dos Testes , Medição de Risco , SalpingectomiaRESUMO
Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients.