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1.
Int J Gynaecol Obstet ; 164(1): 66-74, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37350560

RESUMO

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 , Papillomaviridae
2.
Gynecol Oncol ; 170: 273-281, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36738486

RESUMO

OBJECTIVES: The purpose of this systematic review and meta-analysis was to evaluate the proportion and risk factors of lymphoceles and symptomatic lymphoceles after PLND in early-stage cervical and early-stage high or high-intermediate risk endometrial cancer. METHODS: Studies reporting on the proportion of lymphocele after PLND were conducted in PubMed, Embase and Cochrane Library. Retrieved studies were screened on title/abstract and full text by two reviewers independently. Quality assessment was conducted using the Newcastle Ottowa Scale and the Cochrane risk-of-bias tool. Proportion of lymphocele and possible risk factors were pooled through random-effects meta-analyses. RESULTS: From the 233 studies retrieved, 24 studies were included. The pooled proportion of lymphocele was 14% and of symptomatic lymphocele was 3%. Routinely performing diagnostics was associated with a significantly higher proportion of lymphocele compared to diagnostics performed on indication (21% versus 4%, p < 0.01). Laparotomic surgical approach led to a significantly higher proportion of lymphoceles than laparoscopic surgical approach (18% versus 7%, p = 0.05). The proportion of lymphocele was significantly higher when >15% of the study population underwent additional paraaortic lymph node dissection (PAOLND) opposed to <15% (15% versus 3%, p < 0.01). A mean number of lymph nodes dissected of <21 resulted in a significantly higher pooled proportion of lymphoceles opposed to when the mean number was 21 or higher (19% versus 5%, p = 0.02). Other risk factors analysed were BMI, lymph node metastasis, adjuvant radiotherapy and follow up. There was no sufficient data to detect significant risk factors for the development of symptomatic lymphoceles. CONCLUSION: The pooled proportion of lymphocele was 14% of which symptomatic lymphoceles occurred in 3%. Significant risk factors for the total proportion of lymphoceles were laparotomic approach, decreased number of lymph nodes dissected and additional PAOLND.


Assuntos
Neoplasias do Endométrio , Laparoscopia , Linfocele , Feminino , Humanos , Linfocele/etiologia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Laparoscopia/métodos , Neoplasias do Endométrio/patologia , Pelve , Complicações Pós-Operatórias/etiologia
3.
Gynecol Oncol ; 167(1): 115-122, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36031452

RESUMO

OBJECTIVE: Germline genetic testing is increasingly offered to patients with epithelial ovarian cancer by non-genetic healthcare professionals, so called mainstream genetic testing. The aim of this study was to evaluate the effect of implementing a mainstream genetic testing pathway on the percentage of newly diagnosed patients with epithelial ovarian cancer to whom genetic testing was offered and the genetics-related healthcare costs. METHODS: The possible care pathways for genetic counseling and testing and their associated costs were mapped. Patient files from all newly diagnosed patients with epithelial ovarian cancer before (March 2016 - September 2017) and after (April 2018 - December 2019) implementing our mainstream genetic testing pathway were analyzed. Based on this analysis, the percentage of newly diagnosed patients to whom genetic testing was offered was assessed and genetics-related healthcare costs were calculated using a healthcare payer perspective based on a Diagnosis-Related Group financing approach. RESULTS: Within six months after diagnosis, genetic testing was offered to 56% of patients before and to 70% of patients after implementation of our mainstream genetic testing pathway (p = 0.005). Genetics-related healthcare costs decreased from €3.511,29 per patient before implementation to €2.418,41 per patient after implementation of our mainstream genetic testing pathway (31% reduction, p = 0.000). CONCLUSION: This study shows that mainstream genetic testing leads to a significantly higher proportion of newly diagnosed patients with epithelial ovarian cancer being offered germline genetic testing. In addition, it significantly reduces genetics-related healthcare costs per patient.


Assuntos
Testes Genéticos , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/genética , Feminino , Aconselhamento Genético , Células Germinativas , Custos de Cuidados de Saúde , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia
4.
Gynecol Oncol ; 165(2): 257-263, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35219527

RESUMO

OBJECTIVE: In cervical cancer, sentinel lymph nodes (SLNs) are processed according to the pathological ultrastaging protocol. According to current guidelines, immunohistochemistry with pancytokeratin antibodies is performed in addition to step sectioning with hematoxylin and eosin (H&E), aiding the detection of low volume disease (micrometastasis and isolated tumor cells (ITC)). We studied the added clinical value, and costs, of routine immunohistochemistry (IHC). METHODS: We retrospectively included all FIGO stage IA-IIA1 cervical cancer patients who had undergone SLN procedures at UMC Utrecht from 2008 to 2020. Pathological data were derived from the Dutch Pathology Registry (PALGA) including SLN tumor status and number of slides stained with IHC. RESULTS: In total 234 cervical cancer patients were included. In the 516 surgically resected SLN specimens, 630 SLNs were discovered by the pathologist. Hereof, 579 SLNs from 211 patients were routinely processed with IHC. IHC identified three patients with micrometastasis and five patients with ITC undetected with H&E staining. Thereby, IHC significantly increased the number of patients with low volume disease from 11 (5.3%) to 19 patients (9.1%) (p = 0.04). To achieve this, 3791 slides were stained with IHC at an estimated additional cost of €94,775. In 1.4% (95% CI 0.3%-4.3%) of patients routine use of IHC adjusted the adjuvant treatment. CONCLUSIONS: Routine use of IHC increases detection of low volume disease in cervical cancer SLNs compared to step sectioning with H&E alone by nearly 4%, with an impact on therapeutic strategy-decisions in about 1% of patients. In view of the high associated costs, cost-effectiveness of routine IHC is questionable.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Imuno-Histoquímica , Queratinas , Micrometástase de Neoplasia , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia
5.
Gynecol Oncol ; 163(3): 538-544, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34583837

RESUMO

OBJECTIVE: To evaluate the desire for parenthood and reproductive outcomes of young cervical cancer survivors who underwent fertility-sparing surgery or fertility preservation procedures for invasive cervical cancer. METHODS: All women <45 years who underwent fertility-sparing treatment for invasive cervical cancer in a tertiary referral center in the Netherlands between January 2009 and January 2020 were identified. Fertility-sparing treatment options included Vaginal Radical Trachelectomy (VRT) for patients with early-stage disease and fertility preservation techniques (FP) when requiring Radical Hysterectomy (RH) or chemoradiotherapy. Data on reproductive intentions - and outcomes were retrieved from medical files and questionnaires. RESULTS: 75 patients were identified of whom 34 underwent VRT, 9 RH and 32 had (chemo)radiotherapy. 26 patients started FP of whom 23 (88.5%) successfully preserved fertility through cryopreservation of embryos, oocytes and ovarian tissue. After a median follow-up of 49 months, 5 patients developed recurrent disease and died. Reproductive outcomes were retrieved in 58 patients. 89.6% maintained their desire for parenthood after cancer treatment. Following VRT, we report a pregnancy rate of 61.9% among the patients attempting conception (n = 24). 15 patients conceived 21 pregnancies which resulted in 15 live-births, yielding a live-birth rate of 75.0%. Following RH or (chemo)radiotherapy, 3 surrogate pregnancies were established (21.4%) using frozen-thawed material with good neonatal outcomes. CONCLUSION: Many cervical cancer survivors maintain the desire to become parents eventually. In early-stage disease, VRT shows good reproductive outcomes without compromising oncological safety. For those requiring gonadotoxic treatment fertility preservation and gestational surrogacy provides a promising alternative for achieving a biological offspring.


Assuntos
Preservação da Fertilidade/métodos , Preservação da Fertilidade/psicologia , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Sobreviventes de Câncer/psicologia , Quimiorradioterapia Adjuvante , Estudos de Coortes , Feminino , Seguimentos , Humanos , Histerectomia , Estadiamento de Neoplasias , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Traquelectomia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto Jovem
6.
Gynecol Oncol ; 162(2): 517-525, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34053747

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is often diagnosed late, with a 5-year relative survival of 30.2% for patients with metastatic disease. Residual disease following cytoreductive surgery is an important predictor for poor survival. EOC is characterized by diffuse peritoneal metastases and depositions of small size, challenging a complete resection. Targeted fluorescence imaging is a technique to enhance tumor visualization and can be performed intraoperatively. Folate receptor alpha (FRα) and human epidermal growth factor receptor 2 (HER2) are overexpressed in EOC in 80% and 20% of the cases, respectively, and have been previously studied as a target for intraoperative imaging. OBJECTIVE: To systematically review the literature on the feasibility of FRα and HER2 targeted fluorescence-guided cytoreductive surgery (FGCS) in women with EOC. METHODS: PubMed and Embase were searched for human and animal studies on FGCS targeting either HER2 or FRα in either women with EOC or animal models of EOC. Risk of bias and methodological quality were assessed with the SYRCLE and MINORS tool, respectively. RESULTS: All animal studies targeting either FRα or HER2 were able to detect tumor deposits using intraoperative fluorescence imaging. One animal study targeting HER2 compared conventional cytoreductive surgery (CCS) to FGCS and concluded that FGCS, either without or following CCS, resulted in statistically significant less residual disease compared to CCS alone. Human studies on FGCS showed an increased detection rate of tumor deposits. True positives ranged between 75%-77% and false positives between 10%-25%. Lymph nodes were the main source of false positive results. Sensitivity was 85.9%, though only reported by one human study. CONCLUSION: FGCS targeting either HER2 or FRα appears to be feasible in both EOC animal models and patients with EOC. FGCS is a promising technique, but further research is warranted to validate these results and particularly study the survival benefit.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Imagem Óptica/métodos , Neoplasias Ovarianas/cirurgia , Cirurgia Assistida por Computador/métodos , Animais , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Modelos Animais de Doenças , Reações Falso-Positivas , Estudos de Viabilidade , Feminino , Fluorescência , Receptor 1 de Folato/metabolismo , Humanos , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Imagem Molecular/métodos , Neoplasia Residual , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/diagnóstico por imagem , Ovário/patologia , Ovário/cirurgia , Intervalo Livre de Progressão , Receptor ErbB-2/metabolismo
7.
BJOG ; 128(3): 563-571, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32627934

RESUMO

OBJECTIVE: To investigate the learning curve of robot-assisted laparoscopy in early-stage cervical cancer and quantify impact on oncological outcomes. DESIGN: Observational cohort study. SETTING: Tertiary referral centre with one surgical team. POPULATION: All women with early-stage cervical cancer treated consecutively with robot-assisted laparoscopy between 2007 and 2017. METHODS: With multivariate risk-adjusted cumulative sum analysis (RA-CUSUM), we assessed the learning curve of robot-assisted laparoscopy of a single surgical team based on cervical cancer recurrence. Subsequently, a survival analysis was conducted comparing oncological outcomes of women treated during different phases of the learning curve. MAIN OUTCOME MEASURES: Surgical proficiency based on recurrence, survival rates in the different learning phases. RESULTS: One hundred and sixty-five women with cervical cancer underwent robot-assisted laparoscopy, with a median follow up of 57 months (range 3-132 months). The RA-CUSUM analysis demonstrated two phases of the learning curve: a learning phase of 61 procedures (group 1) and an experienced phase representing the 104 procedures thereafter (group 2). The 5-year disease-free survival was 80.2% in group 1 and 91.1% in group 2 (P = 0.040). Both the 5-year disease-specific survival and overall survival significantly increased after the learning phase. CONCLUSION: The learning phase of robot-assisted laparoscopy in early-stage cervical cancer in this institutional cohort is at least 61 procedures, with higher survival rates in the women treated thereafter. The learning curve of robot-assisted laparoscopy affects oncological outcomes and warrants more attention in the design of future studies. TWEETABLE ABSTRACT: The learning curve of robot-assisted laparoscopy in early-stage cervical cancer affects oncological outcomes and warrants more attention.


Assuntos
Competência Clínica/estatística & dados numéricos , Laparoscopia/mortalidade , Oncologia/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/mortalidade , Cirurgiões/estatística & dados numéricos , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Laparoscopia/educação , Curva de Aprendizado , Oncologia/educação , Pessoa de Meia-Idade , Análise Multivariada , Procedimentos Cirúrgicos Robóticos/educação , Cirurgiões/educação , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
8.
Eur J Surg Oncol ; 45(8): 1425-1431, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31027945

RESUMO

INTRODUCTION: The care for patients with epithelial ovarian cancer(EOC) is organised in eight different geographical regions in the Netherlands. This situation allows us to study differences in practice patterns and outcomes between geographical regions for patients with FIGO stage IIIC and IV. METHODS: We identified all EOC patients who were diagnosed with FIGO stage IIIC or IV between 01.01.2008 and 31.12.2015 from the Netherlands Cancer Registry. Descriptive statistics were used to summarize treatment and treatment sequence(primary cytoreductive surgery(PCS) or neoadjuvant chemotherapy and interval cytoreductive surgery(NACT-ICS)). Moreover, outcome of surgery was compared between geographical regions. Multilevel logistic regression was used to assess whether existing variation is explained by geographical region and case-mix factors. RESULTS: Overall, 6,741 patients were diagnosed with FIGO IIIC or IV disease. There were no differences in the percentage of patients that received any form of treatment between the geographical regions(range 80-86%, P = 0.162). In patients that received cytoreductive surgery and chemotherapy, a significant variation between the geographical regions was observed in the use of PCS and NACT-ICS(PCS: 24-48%, P < 0.001). The percentage of complete cytoreductive surgeries after PCS ranged from 10 to 59%(P < 0.001) and after NACT-ICS from 37 to 70%(P < 0.001). Moreover, geographical region was independently associated with the outcome of surgery, also when adjusted for treatment sequence(P < 0.001). CONCLUSION: We observed a significant variation in treatment approach for advanced EOC between geographical regions in the Netherlands. Furthermore, the probability to achieve no residual disease differed significantly between regions, regardless of treatment sequence. This may suggest that surgical outcomes can be improved across geographical regions.


Assuntos
Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/cirurgia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Ovariectomia/métodos , Sistema de Registros , Idoso , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução/métodos , Intervalo Livre de Doença , Feminino , Geografia , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Avaliação das Necessidades , Terapia Neoadjuvante , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Países Baixos , Neoplasias Ovarianas/patologia , Ovariectomia/mortalidade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
9.
BMC Cancer ; 18(1): 655, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29902979

RESUMO

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/cirurgia
10.
J Eur Acad Dermatol Venereol ; 32(2): 271-275, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28925576

RESUMO

BACKGROUND: Oral immunosuppressive drugs are frequently prescribed in young women with atopic dermatitis (AD). Immunocompromised patients may have a higher risk of developing high-risk HPV infections, cervical intra-epithelial neoplasia (CIN) and cervical carcinoma. Most literature on patients using oral immunosuppressive drugs is available in organ transplant patients. Literature on the risk of developing cervical carcinoma in AD patients treated with oral immunosuppressive drugs is lacking. At this moment, there is no clear guideline/consensus on this topic, but in daily practice, questions arise concerning whether this risk is increased and whether more intensive screening in women using immunosuppressive drugs should take place. OBJECTIVE: To investigate the occurrence of cervical carcinoma in women with AD treated with oral immunosuppressive drugs. METHODS: In this retrospective cohort study in two university medical centres in the Netherlands, all female adult AD patients receiving oral immunosuppressive drugs (cyclosporine A, azathioprine, methotrexate, mycophenolate mofetil, enteric-coated mycophenolate sodium and extended release tacrolimus) for more than 2 months between 1989 and 1 January 2014 were included. Patient files in the national histopathology register were screened for PAP3a, CIN I, CIN II, CIN III and cervical carcinoma. RESULTS: A total of 257 female AD patients with one or more treatment episodes from 1989 until 1 January 2014 were identified and included in this study. In 189 patients (73.5%), results of cervical examination were reported in the national histopathology database. Median total duration of treatment in these 189 women was 407.0 days (IQR 243.0-940.0). No cervical carcinoma during or following immunosuppressive therapy was found in our patient group. CONCLUSIONS: No intensified screening programme for cervical neoplasia seems necessary for women with AD using oral immunosuppressive drugs.


Assuntos
Dermatite Atópica/tratamento farmacológico , Imunossupressores/uso terapêutico , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Administração Oral , Adulto , Feminino , Humanos , Imunossupressores/administração & dosagem , Incidência , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Retrospectivos , Adulto Jovem
11.
BMC Cancer ; 17(1): 110, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28173776

RESUMO

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 , Imiquimode
12.
Eur J Gynaecol Oncol ; 37(1): 63-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27048112

RESUMO

PURPOSE OF INVESTIGATION: Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment. MATERIALS AND METHODS: Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk. RESULTS: 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups. CONCLUSIONS: Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Epiteliais e Glandulares/cirurgia , Nomogramas , Neoplasias Ovarianas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Morbidade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Modelos de Riscos Proporcionais , Adulto Jovem
13.
BMC Cancer ; 16: 132, 2016 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-26897518

RESUMO

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/cirurgia
14.
Gynecol Oncol ; 139(2): 377-84, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26335596

RESUMO

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.


Assuntos
Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Displasia do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias Vaginais/tratamento farmacológico , Neoplasias Vulvares/tratamento farmacológico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/virologia , Feminino , Humanos , Imiquimode , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Neoplasias do Colo do Útero/virologia , Neoplasias Vaginais/virologia , Neoplasias Vulvares/virologia , Displasia do Colo do Útero/virologia
15.
Br J Cancer ; 110(1): 42-8, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24253502

RESUMO

BACKGROUND: For various malignancies, prognostic models have shown to be superior to traditional staging systems in predicting overall survival. The purpose of this study was to validate and compare the performance of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer. METHODS: A multi-institutional epithelial ovarian cancer database was used to identify patients and to evaluate the predictive performance of two nomograms, a prognostic index and FIGO (International Federation of Obstetrics and Gynecology) stage. All patients were treated for advanced-stage epithelial ovarian cancer between January 1996 and January 2009 in 11 hospitals in the eastern part of The Netherlands. RESULTS: In total, 542 patients were found to be eligible. Overall performance did not differ between the three prognostic models and FIGO stage. The discriminative performance for Chi's model was moderately good (c indices 0.65 and 0.68) and for the models of Gerestein and Teramukai reasonable (c indices between 0.60 and 0.62). The c indices of FIGO stage ranged between 0.54 and 0.62. After recalibration, the three models showed almost perfect calibration, whereas calibration of FIGO stage was reasonable. CONCLUSION: The three prediction models showed general applicability and a reasonably well-predictive performance, especially in comparison to FIGO stage. To date, there are no studies available that analyse the impact of these prognostic models on decision-making and patient outcome. Therefore, the usefulness of these models in daily clinical practice remains to be investigated.


Assuntos
Neoplasias Epiteliais e Glandulares/mortalidade , Nomogramas , Neoplasias Ovarianas/mortalidade , Idoso , Carcinoma Epitelial do Ovário , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Países Baixos/epidemiologia , Neoplasias Ovarianas/patologia , Prognóstico , Reprodutibilidade dos Testes , Taxa de Sobrevida
16.
Eur J Cancer ; 46(1): 102-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19900801

RESUMO

OBJECTIVE: Treatment in advanced stage epithelial ovarian cancer (EOC) is based on primary cytoreductive surgery followed by platinum-based chemotherapy. Successful cytoreduction to minimal residual tumour burden is the most important determinant of prognosis. However, extensive surgical procedures to achieve maximal debulking are inevitably associated with postoperative morbidity and mortality. The objective of this study is to determine predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC. METHODS: All patients in the South Western part of the Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007 were identified from the Rotterdam Cancer Registry database. All peri- and postoperative complications within 30 days after surgery were registered and classified according to the definitions of the National Surgical Quality Improvement Programme (NSQIP). To investigate independent predictors of 30-day morbidity, a Cox proportional hazards model with backward stepwise elimination was utilised. The identified predictors were entered into a nomogram. RESULTS: Two hundred and ninety-three patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. 30-day morbidity was seen in 99 (34%) patients. Postoperative morbidity could be predicted by age (P=0.007; odds ratio [OR] 1.034), WHO performance status (P=0.046; OR 1.757), extent of surgery (P=0.1308; OR=2.101), and operative time (P=0.017; OR 1.007) with an optimism corrected c-statistic of 0.68. CONCLUSION: 30-day morbidity could be predicted by age, WHO performance status, operative time and extent of surgery. The generated nomogram could be valuable for predicting operative risk in the individual patient.


Assuntos
Neoplasias Ovarianas/cirurgia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Nomogramas , Neoplasias Ovarianas/patologia , Complicações Pós-Operatórias , Prognóstico , Sistema de Registros , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
17.
Eur J Cancer ; 45(16): 2799-803, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19615887

RESUMO

Residual disease after cytoreductive surgery is an important prognostic factor in patients with advanced stage epithelial ovarian cancer (EOC). Aggressive surgical procedures necessary to achieve maximal cytoreduction are inevitably associated with postoperative morbidity and mortality. To determine causes of postoperative mortality (POM) after surgery for EOC all postoperative deaths in the southwestern part of the Netherlands over a 17-year period were identified and analysed by reviewing medical notes. Between 1989 and 2005, 2434 patients underwent cytoreductive surgery for EOC. Sixty-seven patients (3.1%) died within 30 days after surgery. Postoperative mortality increased with age from 1.5% (26/1765) for the age group 20-69 to 6.6% (32/486) for the age group 70-79 and 9.8% (18/183) for patients aged 80 years or older. Pulmonary failure (18%) and surgical site infection (15%) were the most common causes of death. Only a quarter of deaths resulted from surgical site complications. Our results suggest that causes of postoperative mortality after surgery for EOC are very heterogeneous. Given the impact of general complications, progress in preoperative risk assessment, preoperative preparation and postoperative care seem essential to reduce the occurrence of fatal complications.


Assuntos
Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Ovarianas/cirurgia , Complicações Pós-Operatórias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Neoplasias das Tubas Uterinas/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasia Residual , Países Baixos/epidemiologia , Neoplasias Ovarianas/mortalidade , Prevalência , Adulto Jovem
18.
BJOG ; 116(3): 372-80, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19187369

RESUMO

OBJECTIVE: Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. DESIGN: Retrospective observational study. SETTING: Two teaching hospitals and one university hospital in the south-western part of the Netherlands. POPULATION: Women with advanced stage EOC. METHODS: All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. MAIN OUTCOME MEASURES: The primary outcome measure was OS and the secondary outcome measures were response and PFS. RESULTS: A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease <1 cm (P = 0.004) predicted PFS with a optimism corrected c-statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease <1 cm (P = 0.028) with a optimism corrected c-statistic of 0.67. CONCLUSION: PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.


Assuntos
Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Plaquetas , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Hemoglobinas/metabolismo , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Nomogramas , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do Tratamento
19.
Oncology ; 72(5-6): 293-301, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18198490

RESUMO

OBJECTIVES: Suboptimal debulking (>1 cm residual tumor) results in poor survival rates for patients with an advanced stage of ovarian cancer. The purpose of this study was to develop a prediction model, based on simple preoperative parameters, for patients with an advanced stage of ovarian cancer who are at risk of suboptimal cytoreduction despite maximal surgical effort. METHODS: Retrospective analysis of 187 consecutive patients with a suspected clinical diagnosis of advanced-stage ovarian cancer undergoing upfront debulking between January 1998 and December 2003. Preoperative parameters were Karnofsky performance status, ascites and serum concentrations of CA 125, hemoglobin, albumin, LDH and blood platelets. The main outcome parameter was residual tumor >1 cm. Univariate and multivariate logistic regression was employed for testing possible prediction models. A clinically applicable graphic model (nomogram) for this prediction was to be developed. RESULTS: Serum concentrations of CA 125 and blood platelets in the group with residual tumor >1 cm were higher in comparison to the optimally cytoreduced group (p < 0.0001 and <0.01, respectively). Serum albumin and hemoglobin levels were lower in the group with residual tumor (p < 0.0001 and <0.05, respectively). The frequency of preoperative ascites was higher in the group with residual tumor (p < 0.0005). The prediction model, consisting of CA 125 and albumin, for remaining with residual tumor showed an area under the receiver operating characteristics curve of 0.79. A nomogram for probability of residual tumor >1 cm based on serum levels of CA 125 and albumin was established. CONCLUSION: Postoperative residual tumor despite maximal surgical effort can be predicted by preoperative CA 125 and serum albumin levels. With a nomogram based on these two parameters, probability of postoperative residual tumor in each individual patient can be predicted. This proposed nomogram may be valuable in daily routine practice for counseling and to select treatment modality.


Assuntos
Antígeno Ca-125/sangue , Neoplasia Residual/diagnóstico , Neoplasias Ovarianas/cirurgia , Albumina Sérica/análise , Idoso , Biomarcadores/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasia Residual/sangue , Nomogramas , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Estudos Retrospectivos
20.
Neth Heart J ; 11(11): 447-452, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25696158

RESUMO

BACKGROUND: Pulmonary atresia and intact ventricular septum is characterised by a great morphological variety. Treatment is not uniform. OBJECTIVE: To evaluate our experience with transcatheter valvotomy and balloon dilatation in neonates with pulmonary atresia and intact ventricular septum. DESIGN: Retrospective. METHODS: Between January 1997 and September 2000 five neonates with pulmonary atresia and intact ventricular septum underwent transcatheter valvotomy and balloon dilatation. RESULTS: The catheter intervention was performed at a mean age of 27 days (range 3-95 days). The atretic pulmonary valve was successfully perforated in all neonates. Subsequent balloon dilatation was successful in four neonates. Balloon dilatation was unsuccessful in one patient, who underwent an elective surgical valvotomy of the pulmonary valve after five days. Three patients needed a modified Blalock-Taussig shunt after a mean of 23 days. Four patients required repeated balloon dilatation after a mean of 227 days. Mean follow-up was 2.7 years (range 1-5 years). CONCLUSIONS: Transcatheter perforation of the pulmonary valve membrane and balloon dilatation is a good, safe initial therapy in selected neonates with pulmonary atresia and intact ventricular septum. This procedure can prevent open-heart surgery in these patients in the first months of life.

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