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PURPOSE: Data published in the literature concerning the doses received by fetuses exposed to a 18 F-FDG PET are reassuring but were obtained from small and heterogeneous cohorts, and very few data are available concerning the fetal dose received after exposure to both PET and CT. The present study aimed to estimate the fetal dose received following a PET/CT exposure using methods that include anthropomorphic phantoms of pregnant women applied on a large cohort. PATIENTS AND METHODS: This retrospective multicenter study included 18 pregnant patients in the second and third trimesters. For PET exposure, the fetal volume and mean concentration of radioactivity in the fetus were measured by manually drawing regions of interest. Those data, combined with the time-integrated activities of the fetus and the mother's organs, were entered into the OLINDA/EXM software 2.0 to assess the fetal dose due to PET exposure. To estimate the fetal dose received due to CT exposure, 2 softwares were used: CT-Expo (based on geometric phantom models of nonpregnant patients) and VirtualDose (using pregnant patient phantoms). RESULTS: The fetal dose exposure for PET/CT examination in the second trimester ranged from 5.7 to 15.8 mGy using CT-Expo (mean, 11.6 mGy) and from 5.1 to 11.6 mGy using VirtualDose (mean, 8.6 mGy). In the third trimester, it ranged from 7.9 to 16.6 mGy using CT-Expo (mean, 10.7 mGy) and from 6.1 to 10.7 mGy using VirtualDose (mean, 7.6 mGy). CONCLUSIONS: The estimated fetal doses were in the same range of those previously published and are well below the threshold for deterministic effects. Pregnancy does not constitute an absolute contraindication for a clinically justified hybrid 18 F-FDG PET/CT.
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Feto , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Doses de Radiação , Humanos , Feminino , Gravidez , Feto/diagnóstico por imagem , Feto/efeitos da radiação , Adulto , Imagens de Fantasmas , Estudos RetrospectivosRESUMO
OBJECTIVES: Low grade serous ovarian carcinoma (LGSOC) accounts for 2.5% of all ovarian carcinoma more affects younger women than high grade serous ovarian carcinoma. Hysterectomy is performed routinely for LGSOC treatment, but fertility sparring surgery (FSS) is feasible for some early stages. Currently, there is no study about uterine involvement in LGSOC. We evaluate uterine involvement in LGSOC patients and aim to identify pre-operative predictive factors. METHODS: Retrospective observational study of LGSOC patients treated between January 2000 and May 2022 in the Hospices Civils de Lyon. All cases were viewed, reviewed or approved by an expert pathologist. RESULTS: Among 535 serous ovarian carcinomas, 26 were included. Most patients (73 %) had FIGO III disease. Median OS was 115 months and median PFS was 42 months. Uterine involvement was found in 58 % patients who underwent hysterectomy (14/24), serosal involvement was the most frequent type of involvement (n = 13, 54 %). Myometrial involvement was found in 8 patients (33 %) and was associated with serosal involvement (7/8). Among patients with a macroscopic disease-free uterus during exploratory laparoscopy, 31 % had a microscopic serosal involvement. None patient with presumed early stage (FIGO I) were upstaged due to uterine involvement (serosal or myometrial). In patients with stage FIGO IIII, 72 % of uterine involvement were found. Univariate analysis did not show any predictive factor of myometrial involvement. There was no difference on OS nor PFS between patients with or without myometrial involvement. CONCLUSIONS: In early stages LGSOC, FSS may be considered for selected patients. In advanced stages, hysterectomy should be performed routinely, since no predictive factor for uterine involvement were identified.
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Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/patologia , Útero/cirurgia , Útero/patologia , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/patologia , Estadiamento de NeoplasiasRESUMO
Endometriosis is a common crippling disease in women of reproductive age. Magnetic resonance imaging (MRI) is considered the cornerstone radiological technique for both the diagnosis and management of endometriosis. While its sensitivity, especially in deep infiltrating endometriosis, is superior to that of ultrasonography, many sources of false-positive results exist, leading to a lack of specificity. Hypointense lesions or pseudo-lesions on T2-weighted images include anatomical variants, fibrous connective tissues, benign and malignant tumors, feces, surgical materials, and post treatment scars which may mimic deep pelvic infiltrating endometriosis. False positives can have a major impact on patient management, from diagnosis to medical or surgical treatment. This educational review aims to help the radiologist acknowledge MRI criteria, pitfalls, and the differential diagnosis of deep pelvic infiltrating endometriosis to reduce false-positive results. Critical relevance statement MRI in deep infiltrating endometriosis has a 23% false-positive rate, leading to misdiagnosis. T2-hypointense lesions primarily result from anatomical variations, fibrous connective tissue, benign and malignant tumors, feces, surgical material, and post-treatment scars. Key points ⢠MRI in DIE has a 23% false-positive rate, leading to potential misdiagnosis.⢠Anatomical variations, fibrous connective tissues, neoplasms, and surgical alterations are the main sources of T2-hypointense mimickers.⢠Multisequence interpretation, morphologic assessment, and precise anatomic localization are crucial to prevent overdiagnosis.⢠Gadolinium injection is beneficial for assessing endometriosis differential diagnosis only in specific conditions.
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BACKGROUND: Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. OBJECTIVE: This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. STUDY DESIGN: This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January 2022. RESULTS: Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day 8. CONCLUSION: Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.
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Doença Trofoblástica Gestacional , Mola Hidatiforme , Neoplasias Uterinas , Recém-Nascido , Criança , Gravidez , Humanos , Feminino , Lactente , Estudos Retrospectivos , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/patologia , Estudos de Coortes , Mola Hidatiforme/epidemiologia , Mola Hidatiforme/patologia , Gravidez Múltipla , Doença Trofoblástica Gestacional/patologia , Gonadotropina Coriônica Humana Subunidade beta , Feto/patologia , Gonadotropina CoriônicaRESUMO
OBJECTIVE: Evaluation of the management by first brachytherapy followed by radical hysterectomy (Wertheim type) compared to radical hysterectomy alone (Wertheim type) for the treatment of IB2 cervical cancer. METHODS: Data from women with histologically proven FIGO stage IB2 cervical cancer treated between April 1996 and December 2016 were retrospectively abstracted from twelve French institutions with prospectively maintained databases. RESULTS: Of the 211 patients with FIGO stage IB2 cervical cancer without lymph node involvement included, 136 had surgical treatment only and 75 had pelvic lymph node staging and brachytherapy followed by surgery. The surgery-only group had significantly more adjuvant treatment (29 vs. 3; p = 0.0002). A complete response was identified in 61 patients (81%) in the brachytherapy group. Postoperative complications were comparable (63,2% vs. 72%, p = 0,19) and consisted mainly of urinary (36vs. 27) and digestive (31 vs 22) complications and lymphoceles (4 vs. 1). Brachytherapy had no benefit in terms of progression-free survival (p = 0.14) or overall survival (p = 0.59). However, for tumors of between 20 and 30 mm, preoperative brachytherapy improved recurrence-free survival (p = 0.0095) but not overall survival (p = 0.41). This difference was not observed for larger tumors in terms of either recurrence-free survival (p = 0.55) or overall survival (p = 0.95). CONCLUSION: Our study found that preoperative brachytherapy had no benefit for stage IB2 cervical cancers in terms of recurrence-free survival or overall survival. For tumor sizes between 2 and 3 cm, brachytherapy improves progression-free survival mainly by reducing pelvic recurrences without improving overall survival.
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Braquiterapia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Intervalo Livre de Doença , Estudos Retrospectivos , Estadiamento de Neoplasias , HisterectomiaRESUMO
OBJECTIVE: To evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies. METHODS: The European reference network for rare gynecological tumors (EURACAN G2 domain) aims to improve the diagnosis, management, and treatment of patients with these cancers. Cross-border multidisciplinary tumor boards were initiated to facilitate intercollegiate clinical discussions across Europe and increase patients' access to specialist treatment recommendations and clinical trials. All G2 healthcare providers were invited to participate in monthly multidisciplinary meetings. Patient data were collected using a standardized form and case summaries were distributed before each meeting. After each tumor board, a meeting summary with treatment recommendations was sent to all participants and the project manager at the coordinating center. The multidisciplinary tumor board format and outcomes were regularly discussed at G2 domain meetings. Anonymized clinical data and treatment recommendations were registered in a prospective database. For this report, clinical data were collected between November 2017 and December 2020 and follow-up data retrieved until May 2021. RESULTS: During the 3-year period, 31 multidisciplinary tumor boards were held with participants from 10 countries and 20 centers. 91 individual patients were discussed between one and six times for a total of 109 case discussions. Follow-up data were retrieved from 64 patients and 80 case discussions. Adherence to treatment recommendations was 99%. Multidisciplinary tumor board recommendations resulted in 11 patients getting access to off-label treatment and one patient being enrolled in a clinical trial in another European country. 14/91 patients were recommended for surveillance only when additional treatment had been considered locally. CONCLUSION: Cross-border multidisciplinary tumor boards enable networking and clinical collaboration between healthcare professionals in different countries. Surveillance strategies, off-label drug use, and increased participation in clinical trials are possible benefits to patients with rare gynecological tumors.
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Neoplasias dos Genitais Femininos , Feminino , Humanos , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/terapia , Uso Off-Label , Pessoal de Saúde , Europa (Continente)RESUMO
Hydatidiform moles (HMs) are divided into two types: partial hydatidiform mole (PHM) which is most often diandric monogynic triploid and complete hydatidiform mole (CHM) which is most often diploid androgenetic. Morphological features and p57 immunostaining are routinely used to distinguish both entities. Genetic analyses are required in challenging cases to determine the parental origin of the genome and ploidy. Some gestations cannot be accurately classified however. We report a case with atypical pathologic and genetic findings that correspond neither to CHM nor to PHM. Two populations of villi with divergent and discordant p57 expression were observed: morphologically normal p57 + villi and molar-like p57 discordant villi with p57 + stromal cells and p57 - cytotrophoblasts. Genotyping of DNA extracted from microdissected villi demonstrated that the conceptus was an androgenetic/biparental mosaic, originating from a zygote with triple paternal contribution, and that only the p57 - cytotrophoblasts were purely androgenetic, increasing the risk of neoplastic transformation.
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Mola Hidatiforme , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Neoplasias Uterinas/patologia , Mosaicismo , Diploide , Genótipo , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Imuno-Histoquímica , Mola Hidatiforme/genética , Mola Hidatiforme/metabolismoRESUMO
Background Immune checkpoint immunotherapy (CPI) targeting PD1/PD-L1 has been shown to be an effective treatment for gestational trophoblastic neoplasia (GTN). This includes those with multidrug resistance, ultra-high risk disease and ETT/PSTT subtypes that are inherently chemotherapy resistant, but there is also emerging evidence in low-risk disease. Objectives We set out to generate an overview of the current data supporting the use of CPI for GTN in both high risk and low risk disease and to consider future research goals and directions in order to implement CPI in current treatment guidelines. Methods We identified and reviewed the published data on the use of CPI agents in GTN. Outcome 133 patients were identified who had been treated with CPI for GTN with pembrolizumab (23), avelumab (22), camrelizumab (57), toripalimab (15) or other anti-PD-1 agents (16), of whom 118 had high risk disease, relapse or multi drug resistant disease, and 15 low risk disease. Overall 85 patients achieved complete remission, 77 (of 118) with high risk disease and 8 (of 15) with low risk disease. 1 patient with complete remission in the high risk group developed a relapse 22 months after anti-PD-1 treatment had been stopped. Treatment was generally well tolerated across studies. Conclusions and Outlook The majority of high risk patients (77/118) treated with CPI are cured and this is particularly relevant amongst those with chemotherapy resistant disease who otherwise have very limited treatment options. Priorities for future research include determining whether these agents have a role earlier in the disease course, the utility of combination with chemotherapy, and effects on future fertility. Treatment availability remains a concern due to the high price of these agents.
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BACKGROUND: Liver metastases of gestational trophoblastic neoplasia (GTN) are rare, but associated with poor prognosis. The additional concomitant presence of brain or intra-abdominal metastases, with liver metastases has been described as worsening factors, but the literature on this topic is reduced. OBJECTIVE: To estimate the overall mortality, specific hepatic morbidity, and mortality, and to identify prognostic factors for patients with GTN and liver metastases. METHOD: The medical records of 26 GTN patients with liver metastases registered in the French Center for Trophoblastic Diseases and treated between November 1999 and December 2019 were reviewed. Overall survival was described using Kaplan-Meier estimates. Prognostic factors were identified using univariate and multivariate Cox analyses. RESULTS: The 5-year overall survival rate was 60.7% for all patients with liver metastasis. The survival rate was higher in patients who achieved complete remission after first-line chemotherapy than in those who did not (100% vs 20%, p = 0.001). The only factor independently associated with prognosis was the presence of 6 or more liver metastases (5-year survival, 16.7% vs. 82.4% otherwise; HR =11.1, 95%CI, 2.3-53.1; p = 0.003). None of the five patients with a single liver metastasis died. CONCLUSION: GTN with liver metastasis is very rare (1.6%). The prognosis of patients seems to be improving. The results of this study are also reassuring for patients with complete remission after first-line combination chemotherapy, as well as for those with a single liver metastasis.
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Doença Trofoblástica Gestacional , Neoplasias Hepáticas , Gravidez , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Hepáticas/secundárioRESUMO
OBJECTIVE: Excisional procedures have a central role in the management of adenocarcinoma in situ of the cervix (AIS). We aimed to evaluate the relationship between the excisional specimen dimensions and the endocervical margin status. METHODS: We conducted a multicentric retrospective study in seven French centers. All cases with proven AIS on a colposcopic biopsy and undergoing an excisional procedure afterwards were included in the analysis. We evaluated the impact of excision length, along with the lateral and anteroposterior diameters on the endocervical margin status. An additional subgroup analysis of the impact of maternal age on endocervical margin status was also conducted. RESULTS: Of the 101 cases of AIS diagnosed on initial biopsy, 95 underwent a primary excisional procedure, among which 80% (n = 76/95) had uninvolved endocervical margins and 20% (n = 19/95) had positive endocervical margins. The excisional specimen length was not significantly related to the endocervical margin status. Conversely, both lateral and antero-posterior diameters were significantly correlated with the negative endocervical margins status: OR = 1,19, 95% CI [1.03, 1.40], p = 0.025, for the lateral diameter and OR = 1.34, 95% CI [1.14, 1.64], p = 0.001 for the antero-posterior diameter. The median lateral diameter was 20 mm, IQR (18, 24) in case of endocervical negative margins vs. 18 mm IQR (15, 24) in case of positive endocervical margins (p = 0.039), and the median anteroposterior diameter was 17 mm IQR (15, 20) in case of negative endocervical margins vs 14 mm IQR (11, 15) in case of positive endocervical margins (p = 0.004), respectively. Additionally, in patients over 45 years old, endocervical margin were more likely to be positive despite similar excisional dimensions (7/17 (41%) of positive endocercival margins before 45 years old vs 12/78 (15%) after, p = 0.039) CONCLUSIONS: Endocervical margin statues were significantly related to the transverse diameters (lateral and anteroposterior diameters), but not to the excision specimen length. Reducing the excised length may lead to fewer post-procedure complications but would still allow to obtain a large proportion of negative endocervical margins.
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Adenocarcinoma in Situ , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Colo do Útero/cirurgia , Colo do Útero/patologia , Adenocarcinoma in Situ/cirurgia , Adenocarcinoma in Situ/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Conização , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Margens de ExcisãoRESUMO
OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.
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INTRODUCTION: Gestational trophoblastic neoplasia (GTN) is a group of rare tumors characterized by abnormal trophoblastic proliferation following pregnancy including invasive moles, choriocarcinomas, and intermediate trophoblastic tumors (ITT). Although the treatment and follow-up of GTN has been heterogeneous, globally the emergence of expert networks has helped to harmonize its management. AREAS COVERED: We provide an overview of the current knowledge, diagnosis, and management strategies in GTN and discuss innovative therapeutic options under investigation. While chemotherapy has been the historical backbone of GTN treatment, promising drugs such as immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway and anti-angiogenic tyrosine kinase inhibitors are currently being investigated remodeling the therapeutical landscape of trophoblastic tumors. EXPERT OPINION: Chemotherapy regimens for GTN have potential long-term effects on fertility and quality of life, making innovative and less toxic therapeutic approaches necessary. Immune checkpoint inhibitors have shown promise in reversing immune tolerance in GTN and have been evaluated in several trials. However, immunotherapy is associated with rare but life-threatening adverse events and evidence of immune-related infertility in mice, highlighting the need for further research and careful consideration of its use. Innovative biomarkers could help personalize GTN treatments and reduce chemotherapy burden in some patients.
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Doença Trofoblástica Gestacional , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Animais , Camundongos , Inibidores de Checkpoint Imunológico/efeitos adversos , Qualidade de Vida , Doença Trofoblástica Gestacional/terapia , Doença Trofoblástica Gestacional/tratamento farmacológico , Neoplasias Uterinas/terapiaRESUMO
Importance: Preoperative mapping of deep pelvic endometriosis (DPE) is crucial as surgery can be complex and the quality of preoperative information is key. Objective: To evaluate the Deep Pelvic Endometriosis Index (dPEI) magnetic resonance imaging (MRI) score in a multicenter cohort. Design, Setting, and Participants: In this cohort study, the surgical databases of 7 French referral centers were retrospectively queried for women who underwent surgery and preoperative MRI for DPE between January 1, 2019, and December 31, 2020. Data were analyzed in October 2022. Intervention: Magnetic resonance imaging scans were reviewed using a dedicated lexicon and classified according to the dPEI score. Main outcomes and measures: Operating time, hospital stay, Clavien-Dindo-graded postoperative complications, and presence of de novo voiding dysfunction. Results: The final cohort consisted of 605 women (mean age, 33.3; 95% CI, 32.7-33.8 years). A mild dPEI score was reported in 61.2% (370) of the women, moderate in 25.8% (156), and severe in 13.1% (79). Central endometriosis was described in 93.2% (564) of the women and lateral endometriosis in 31.2% (189). Lateral endometriosis was more frequent in severe (98.7%) vs moderate (48.7%) disease and in moderate vs mild (6.7%) disease according to the dPEI (P < .001). Median operating time (211 minutes) and hospital stay (6 days) were longer in severe DPE than in moderate DPE (operating time, 150 minutes; hospital stay 4 days; P < .001), and in moderate than in mild DPE (operating time; 110 minutes; hospital stay, 3 days; P < .001). Patients with severe disease were 3.6 times more likely to experience severe complications than patients with mild or moderate disease (odds ratio [OR], 3.6; 95% CI, 1.4-8.9; P = .004). They were also more likely to experience postoperative voiding dysfunction (OR, 3.5; 95% CI, 1.6-7.6; P = .001). Interobserver agreement between senior and junior readers was good (κ = 0.76; 95% CI, 0.65-0.86). Conclusions and Relevance: The findings of this study suggest the ability of the dPEI to predict operating time, hospital stay, postoperative complications, and de novo postoperative voiding dysfunction in a multicenter cohort. The dPEI may help clinicians to better anticipate the extent of DPE and improve clinical management and patient counseling.
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Endometriose , Humanos , Feminino , Adulto , Endometriose/diagnóstico por imagem , Endometriose/cirurgia , Endometriose/complicações , Estudos de Coortes , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.
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Gestational trophoblastic diseases derived from the chorionic-type intermediate trophoblast include benign placental site nodule (PSN) and malignant epithelioid trophoblastic tumor (ETT). Among PSNs, the World Health Organization classification introduced a new entity named atypical placental site nodule (APSN), corresponding to an ETT precursor, for which diagnostic criteria remain unclear, leading to a risk of overdiagnosis and difficulties in patient management. We retrospectively studied 8 PSNs, 7 APSNs, and 8 ETTs to better characterize this new entity and performed immunohistochemical analysis (p63, human placental lactogen, Cyclin E, and Ki67), transcriptional analysis using the NanoString method to quantify the expression of 760 genes involved in the main tumorigenesis pathways, and RNA sequencing to identify fusion transcripts. The immunohistochemical analysis did not reveal any significant difference in Cyclin E expression among the 3 groups (P = .476), whereas the Ki67 index was significantly (P < .001) higher in ETT samples than in APSN and PSN samples. None of the APSN samples harbored the LPCAT1::TERT fusion transcripts, in contrast to 1 of 6 ETT samples, as previously described in 2 of 3 ETT samples. The transcriptomic analysis allowed robust clustering of ETTs distinct from the APSN/PSN group but failed to differentiate APSNs from PSNs. Indeed, only 7 genes were differentially expressed between PSN and APSN samples; CCL19 upregulation and EPCAM downregulation were the most distinguishing features of APSNs. In contrast, 80 genes differentiated ETTs from APSNs, establishing a molecular signature for ETT. Gene set analysis identified significant enrichments in the DNA damage repair, immortality and stemness, and cell cycle signaling pathways when comparing ETTs and APSNs. These results suggested that APSN might not represent a distinct entity but rather a transitional stage between PSN and ETT. RNA sequencing and the transcriptional signature of ETT described herein could serve as triage for APSN from curettage or biopsy material, enabling the identification of cases that need further clinical investigations.
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Doença Trofoblástica Gestacional , Tumor Trofoblástico de Localização Placentária , Neoplasias Uterinas , Feminino , Humanos , Gravidez , Tumor Trofoblástico de Localização Placentária/química , Tumor Trofoblástico de Localização Placentária/metabolismo , Tumor Trofoblástico de Localização Placentária/patologia , Ciclina E , Placenta/patologia , Antígeno Ki-67 , Estudos Retrospectivos , Neoplasias Uterinas/diagnóstico , Doença Trofoblástica Gestacional/genética , Doença Trofoblástica Gestacional/patologiaRESUMO
BACKGROUND: The aim of this study was to assess current European practices in the management of patients with advanced epithelial ovarian cancer in 2021. METHODS: A 58-question electronic survey was distributed anonymously to the members of six European learned societies. Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. RESULTS: A total of 171 participants from 17 European countries responded to emailed surveys. Most participants were experienced practitioners (superior than 15 years of experience) specializing in gynecology-obstetrics (29.8%), surgical oncology (25.1%), and oncogynecology (21.6%). According to most (64.8%) participants, less than 50% of patients were eligible for primary debulking surgery. Variations in the rate of primary debulking surgery depending on the country of origin of the practitioners were observed in this study. The LION study criteria were applied in 70.4% of cases during PDS and 27.1% after chemotherapy. In cases of BRCA1-2 mutations, olaparib was given by 75.0-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. CONCLUSIONS: This study sheds light on current practices and attitudes regarding the management of patients with advanced epithelial ovarian cancer in Europe in 2021.
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Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/terapia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Inquéritos e Questionários , Europa (Continente) , Estadiamento de Neoplasias , Procedimentos Cirúrgicos de Citorredução , Terapia NeoadjuvanteRESUMO
PURPOSE: There is a need for innovative treatments in women with gestational trophoblastic tumors (GTT) resistant to chemotherapy. The TROPHIMMUN trial assessed the efficacy of avelumab in patients with resistance to single-agent chemotherapy (cohort A), or to polychemotherapy (cohort B). Cohort B outcomes are reported here. METHODS: In the cohort B of this phase 2 multicenter trial (NCT03135769), women with GTT progressing after polychemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. The primary endpoint was the rate of hCG normalization enabling treatment discontinuation (2-stage Simon design). RESULTS: Between February 2017 and August 2020, 7 patients were enrolled. Median age was 37 years (range: 29-47); disease stage was I or III in 42.9% and 57.1%; FIGO score was 9-10 in 28.6%, 11 in 28.6%, and 16 in 14.3%, respectively. Median follow-up was 18.2 months. One patient (14.3%) experienced hCG normalization enabling treatment discontinuation. However, resistance to avelumab was observed in the remaining 6 patients (85.7%). The cohort B was stopped for futility. Grade 1-2 treatment-related adverse events occurred in 57.1%, most commonly fatigue (42.9%), nausea, diarrhea, infusion-related reaction, muscle pains, dry eyes (each 14.3%). The median resistance-free survival was 1.4 months (95% CI 0.7-5.3). CONCLUSIONS: Although avelumab is active in patients with single-agent chemotherapy-resistant GTT (cohort A), it was associated with limited efficacy in patients with resistance to polychemotherapy (cohort B). The prognosis of patients with polychemotherapy resistance remains poor, and innovative immunotherapy-based therapeutic combinations are needed.
Assuntos
Anticorpos Monoclonais Humanizados , Doença Trofoblástica Gestacional , Adulto , Feminino , Humanos , Gravidez , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Prognóstico , Pessoa de Meia-IdadeRESUMO
Objective: The aim of the present study was to evaluate evolution and prognosis of mucinous ovarian carcinomas (mOC), with respect to the two invasive patterns: expansile and infiltrative invasion. Methods: This was a descriptive, retrospective, multicenter study conducted in 13 French centres from 1 January 2001 to 31 December 2019. All patients operated on for epithelial ovarian neoplasia of the mucinous type (infiltrative/expansile) were included, whether the surgery was performed immediately or after neoadjuvant chemotherapy. Results: A total of 94 women with mucinous carcinomas were included in the present study. Mucinous tumours were divided into 35 expansile (37%) and 59 infiltrative (63%) mOC. There was a statistically significant difference in early and late stages at initial diagnosis between expansile and infiltrative mOC. None of the expansile mOC showed metastatic lymph nodes, whereas almost a quarter of the infiltrative mOC were metastatic to the pelvic/para-aortic region. There was a clear difference in RFS, in favour of expansile mOC, with 90% survival at 5 years, compared with 60% for infiltrative mOC. Conclusions: Although infiltrative and expansile mOC belong to the same histological family, they present many distinctions in clinical presentation, histological invasion, and disease course.
RESUMO
BACKGROUND: Spontaneous hemoperitoneum in pregnancy (SHiP) is a complication of endometriosis. We describe the clinical characteristics and outcomes of mother and fetus in 11 new cases of SHiP with endometriosis and 43 cases reported in the literature since 1995. MATERIAL AND METHODS: The 60 maternity hospitals in the Auvergne-Rhône-Alpes region in France were contacted to identify cases of SHiP associated with endometriosis. In parallel, a systematic review of the literature used the PRISMA chart to report published cases. RESULTS: Fifty-four cases of SHIP associated with endometriosis are presented. Twenty-four patients (44%) conceived with assisted reproductive techniques. Hemoperitoneum occurred before delivery in 47/54 cases (87%).The average gestational age of occurrence was 27 weeks (13 weeks to 40+6 weeks). An hypovolemic shock was present in 24/51 (47%) of patients. Forty-six women (85%) were treated by laparotomy, 5 (9%) by laparoscopy, 2 (2%) by interventional radiology. The hemorrhage site was in the mediolateral compartment of the pelvis in 29 cases (54%), corresponding to bleeding from vessels in the broad ligament in 24/29 (83%) of these cases. The mean estimated blood loss was 1957 mL (150-7500 mL). Emergency peripartum hysterectomy was required in 3/54 cases (6%). There were no maternal deaths. The average gestational age at birth was 30 weeks (13+2 weeks to 42 weeks). The fetus died in 19/64 cases (30%). CONCLUSION: SHiP is an underestimated potentially fatal complication of endometriosis. Maternal salvage by emergency laparotomy is usually required to identify and treat the bleeding site. Fetal prognosis remains poor.
Assuntos
Endometriose , Complicações na Gravidez , Feminino , Feto , Idade Gestacional , Hemoperitônio , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
BACKGROUND: This study compares morbidity and mortality associated with retroperitoneal and transperitoneal para-aortic lymphadenectomy (PAAL) for pretherapeutic nodal staging of locally advanced cervical cancers (FIGO IB3-IVA). METHODS: Pre-, per- and postoperative data of patients treated for locally advanced stage cervical cancer between 1999 and 2018 in 12 French referral centers (FRANCOGYN Study Group) were retrospectively collected. RESULTS: The study was conducted using a sample of 448 patients, of whom 223 (49,8%) underwent retroperitoneal (group 1) and 225 (50,2%) had transperitoneal PAAL (group 2). No differences were noted concerning clinical and histological characteristics between the two groups. Among these 448 patients, 23 (5,1%) had an intraoperative complication (9 (2,0%) in group 1 and 14 (3,1%) in group 2, p = 0.28) and 47 (10,5%) had a postoperative complication (22 (4,9%) in group 1 and 25 (5,6%) in group 2, p = 0.44), only one of which required revision surgery but the patient died. The length of hospital stay was significantly shorter in group 1 than in group 2 (3.97 versus 4.88 days, p < 0.001). There was no significant difference in mortality between the two groups; 34 of 223 patients in group 1 (15.3%) and 40 of 225 patients in group 2 (15.6%) died (HR = 0.968, 95% CI [0.591-1.585]). There was no significant difference in recurrence-free or overall survival between the two groups. CONCLUSION: Retroperitoneal PAAL appears as a valuable and safety surgical route for nodal staging in locally advanced cervical cancer compared with standard transperitoneal PAAL.