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RESEARCH QUESTION: Can a saliva-based miRNA signature for endometriosis-associated infertility be designed and validated by analysing the human miRNome? DESIGN: The prospective ENDOmiARN study (NCT04728152) included 200 saliva samples obtained between January 2021 and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy, magnetic resonance imaging, or both. Patients diagnosed with endometriosis were allocated to one of two groups according to their fertility status. Data analysis consisted of identifying a set of miRNA biomarkers using next-generation sequencing, and development of a saliva-based miRNA signature of infertility among patients with endometriosis based on a random forest model. RESULTS: Among the 153 patients diagnosed with endometriosis, 24% (nâ¯=â¯36) were infertile and 76% (nâ¯=â¯117) were fertile. Small RNA-sequencing of the 153 saliva samples yielded approximately 3712 M raw sequencing reads (from â¼13.7 M to â¼39.3 M reads/sample). Of the 2561 known miRNAs, the feature selection method generated a signature of 34 miRNAs linked to endometriosis-associated infertility. After validation, the most accurate signature model had a sensitivity, specificity and area under the curve of 100%. CONCLUSION: A saliva-based miRNA signature for endometriosis-associated infertility is reported. Although the results still require external validation before using the signature in routine practice, this non-invasive tool is likely to have a major effect on care provided to women with endometriosis.
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Endometriose , Infertilidade Feminina , Infertilidade , MicroRNAs , Feminino , Humanos , Endometriose/complicações , Endometriose/diagnóstico , Endometriose/genética , Infertilidade Feminina/genética , Infertilidade Feminina/patologia , MicroRNAs/genética , Estudos Prospectivos , SalivaRESUMO
OBJECTIVE: To evaluate a saliva diagnostic test (Endotest®) for endometriosis compared with the conventional algorithm. DESIGN: A cost-effectiveness analysis with a decision-tree model based on literature data. SETTING: France. POPULATION: Women with chronic pelvic pain. METHODS: Strategy I is the French algorithm, representing the comparator. For strategy II, all patients have an Endotest®. For strategy III, patients undergo ultrasonography to detect endometrioma and patients with no endometrioma detected have an Endotest®. For strategy IV, patients with no endometrioma detected on ultrasonography undergo pelvic magnetic resonance imaging (MRI) to detect endometrioma and/or deep endometriosis. An Endotest® is then performed for patients with a negative result on MRI. MAIN OUTCOMES MEASURES: Costs and accuracy rates and incremental cost-effectiveness ratios (ICERs). Three analyses were performed with an Endotest® priced at 500, 750, and 1000. Probabilistic sensitivity analysis was conducted with Monte Carlo simulations. RESULTS: With an Endotest® priced at 750, the cost per correctly diagnosed case was 1542, 990, 919 and 1000, respectively, for strategies I, II, III and IV. Strategy I was dominated by all other strategies. Strategies IV, III and II were, respectively, preferred for a willingness-to-pay threshold below 473, between 473 and 4670, and beyond 4670 per correctly diagnosed case. At a price of 500 per Endotest®, strategy I was dominated by all other strategies. At 1000, the ICERs of strategies II and III were 724 and 387 per correctly diagnosed case, respectively, compared with strategy I. CONCLUSION: The present study demonstrates the value of the Endotest® from an economic perspective.
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Endometriose , MicroRNAs , Saliva , Feminino , Humanos , Análise Custo-Benefício , Endometriose/diagnóstico , Endometriose/genética , MicroRNAs/análise , Anos de Vida Ajustados por Qualidade de Vida , Saliva/química , Ultrassonografia , Técnicas de Diagnóstico Obstétrico e Ginecológico/economiaRESUMO
Endometriosis, defined by the presence of endometrium-like tissue outside the uterus, affects 2-10% of the female population, i.e., around 190 million women, worldwide. The aim of the prospective ENDO-miRNA study was to develop a bioinformatics approach for microRNA-sequencing analysis of 200 saliva samples for miRNAome expression and to test its diagnostic accuracy for endometriosis. Among the 200 patients, 76.5% (n = 153) had confirmed endometriosis and 23.5% (n = 47) had no endometriosis (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). The number of expressed miRNAs ranged from 1250 (outlier) to 2561 per sample. Some 2561 miRNAs were found to be differentially expressed in the saliva samples of patients with endometriosis compared with the control patients. Among these, 1.17% (n = 30) were up- or downregulated. Among these, the F1-score, sensitivity, specificity, and AUC ranged from 11-86.8%, 5.8-97.4%, 10.6-100%, and 39.3-69.2%, respectively. Here, we report a bioinformatic approach to saliva miRNA sequencing and analysis. We underline the advantages of using saliva over blood in terms of ease of collection, reproducibility, stability, safety, non-invasiveness. This report describes the whole saliva transcriptome to make miRNA quantification a validated, standardized, and reliable technique for routine use. The methodology could be applied to build a saliva signature of endometriosis.
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Endometriose , MicroRNAs , Biologia Computacional , Endometriose/diagnóstico , Endometriose/genética , Endometriose/metabolismo , Endométrio/metabolismo , Feminino , Humanos , MicroRNAs/metabolismo , Estudos Prospectivos , Reprodutibilidade dos Testes , Saliva/metabolismoRESUMO
OBJECTIVE: To assess the impact of type of surgery for colorectal endometriosis-rectal shaving or discoid resection or segmental colorectal resection-on complications and surgical outcomes. DATA SOURCES: We performed a systematic review of all English- and French-language full-text articles addressing the surgical management of colorectal endometriosis, and compared the postoperative complications according to surgical technique by meta-analysis. The PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases were searched for relevant studies published before March 27, 2020. The search strategy used the following Medical Subject Headings terms: ("bowel endometriosis" or "colorectal endometriosis") AND ("surgery for endometriosis" or "conservative management" or "radical management" or "colorectal resection" or "shaving" or "full thickness resection" or "disc excision") AND ("treatment", "outcomes", "long term results" and "complications"). METHODS OF STUDY SELECTION: Two authors conducted the literature search and independently screened abstracts for inclusion, with resolution of any difference by 3 other authors. Studies were included if data on surgical management (shaving, disc excision, and/or segmental resection) were provided and if postoperative outcomes were detailed with at least the number of complications. The risk of bias was assessed according to the Cochrane recommendations. TABULATION, INTEGRATION, AND RESULTS: Of the 168 full-text articles assessed for eligibility, 60 were included in the qualitative synthesis. Seventeen of these were included in the meta-analysis on rectovaginal fistula, 10 on anastomotic leakage, 5 on anastomotic stenosis, and 9 on voiding dysfunction <30 days. The mean complication rate according to shaving, disc excision, and segmental resection were 2.2%, 9.7%, and 9.9%, respectively. Rectal shaving was less associated with rectovaginal fistula than disc excision (odds ratio [OR]â¯=â¯0.19; 95% confidence interval [CI], 0.10-0.36; p <.001; I2â¯=â¯33%) and segmental colorectal resection (ORâ¯=â¯0.26; 95% CI, 0.15-0.44; p <.001; I2â¯=â¯0%). No difference was found in the occurrence of rectovaginal fistula between disc excision and segmental colorectal resection (ORâ¯=â¯1.07; 95% CI, 0.70-1.63; pâ¯=â¯.76; I2â¯=â¯0%). Rectal shaving was less associated with leakage than disc excision (ORâ¯=â¯0.22; 95% CI, 0.06-0.73; pâ¯=â¯.01; I2â¯=â¯86%). No difference was found in the occurrence of leakage between rectal shaving and segmental colorectal resection (ORâ¯=â¯0.32; 95% CI, 0.10-1.01; pâ¯=â¯.05; I2â¯=â¯71%) or between disc excision and segmental colorectal resection (ORâ¯=â¯0.32; 95% CI, 0.30-1.58; pâ¯=â¯.38; I2â¯=â¯0%). Disc excision was less associated with anastomotic stenosis than segmental resection (ORâ¯=â¯0.15; 95% CI, 0.05-0.48; pâ¯=â¯.001; I2â¯=â¯59%). Disc excision was associated with more voiding dysfunction <30 days than rectal shaving (ORâ¯=â¯12.9; 95% CI, 1.40-119.34; pâ¯=â¯.02; I2â¯=â¯0%). No difference was found in the occurrence of voiding dysfunction <30 days between segmental resection and rectal shaving (ORâ¯=â¯3.05; 95% CI, 0.55-16.87; pâ¯=â¯.20; I2â¯=â¯0%) or between segmental colorectal and discoid resections (ORâ¯=â¯0.99; 95% CI, 0.54-1.85; pâ¯=â¯.99; I2â¯=â¯71%). CONCLUSION: Colorectal surgery for endometriosis exposes patients to a risk of severe complications such as rectovaginal fistula, anastomotic leakage, anastomotic stenosis, and voiding dysfunction. Rectal shaving seems to be less associated with postoperative complications than disc excision and segmental colorectal resection. However, this technique is not suitable for all patients with large bowel infiltration. Compared with segmental colorectal resection, disc excision has several advantages, including shorter operating time, shorter hospital stay, and lower risk of postoperative bowel stenosis.
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Procedimentos Cirúrgicos do Sistema Digestório , Endometriose/cirurgia , Doenças Retais/cirurgia , Adulto , Colo Sigmoide/cirurgia , Bases de Dados Factuais , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Endometriose/diagnóstico , Endometriose/epidemiologia , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Doenças Retais/diagnóstico , Doenças Retais/epidemiologia , Fístula Retovaginal/diagnóstico , Fístula Retovaginal/epidemiologia , Fístula Retovaginal/cirurgia , Reto/cirurgia , Resultado do TratamentoRESUMO
In the original publication [...].
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OBJECTIVE: To evaluate the outcomes associated with each therapeutic option for patients diagnosed with interstitial pregnancy (IP). METHODS: We conducted a multicentric retrospective cohort study within the departments of Gynecology and Obstetrics involved in the Francogent research group. Women treated for an interstitial pregnancy between January 2008 to December 2019 were included. Three therapeutic options were evaluated: surgical treatment (ST); in situ methotrexate combined with systemic methotrexate (IS-MTX); and systemic methotrexate (IM-MTX). Success of first-line treatment was defined by hCG negativation (<5I U/L). Secondary outcomes included the need for secondary surgical procedure, secondary medical treatment, emergency surgery, postoperative complications, duration of hospitalization, and delay before hCG negativation. RESULTS: A total of 98 patients were managed for IP: 42 (42.9%) patients had IM-MTX; 34 (34.7%) had IS-MTX; and 22 (22.4%) had ST. First-line treatment was successful in all patients of the ST group (22/22, 100%), in 31% of patients within the IM-MTX group (13/42) and 70.6% (24/34) in the IS-MTX group. The sole parameter associated with the risk of treatment failure was the mode of methotrexate administration. The size of the gestational sac or the presence of fetal heartbeat was not associated with decreased medical treatment (IS or IM-MTX) efficiency. CONCLUSION: Either ST or IS-MTX are good options for IP treatment associated with high success rates. A single-dose regimen of IM-MTX is less efficient than IS-MTX or ST. Symptomatic patients with severity criteria should always undergo emergency surgery. IP remains a high-risk condition that should be managed, whenever possible, in referral centers to potentialize the chances of favorable outcomes.
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Abortivos não Esteroides , Gravidez Intersticial , Gravidez , Humanos , Feminino , Metotrexato/uso terapêutico , Abortivos não Esteroides/uso terapêutico , Gravidez Intersticial/tratamento farmacológico , Estudos Retrospectivos , Injeções Intramusculares , Resultado do TratamentoRESUMO
OBJECTIVE: The objective of our study was to study the impact of discoid excision for deep endometriosis (DE) with colorectal involvement on fertility outcomes. METHODS: 49 patients with a desire for pregnancy treated with discoid excision for colorectal endometriosis in our endometriosis expert center between January 2015 and August 2020 were selected from our prospectively maintained database. Indications for surgery were either infertility and / or pelvic pain. Postoperative complications were graded according to the Clavien-Dindo classification. Fertility outcomes, both spontaneous and post-ART pregnancies, were analyzed. RESULTS: Among the 49 patients who underwent discoid excision exclusively (no other digestive resection) with a desire to conceive, 25 had a pregnancy after surgery and 24 did not. Double discoid excision was performed in 6.1 % of the cases (3/49). A colpectomy was performed in 12.2 % of the patients (6/49), and a protective stoma in 12.2 % (6/49). Fenestration of endometriomas was performed in 28.6 % of the patients (14/49), and parametrectomy in 40.8 % (20/49). The postoperative complication rate was 24.5 % (12/49) including 10.2 % (5/49) grade I, 12.2 % (6/49) grade II, and 2 % (1/49) grade III. Prior to surgery, 28 (57.1 %) patients had infertility including 13 (52 %) that successfully conceived following surgery and 15 (62.5 %) that remain infertile. Spontaneous pregnancy was achieved in 60 % (15/25) of infertile patients' prior surgery. The live-birth rate in patients conceiving spontaneously was 75 % (12/16). CONCLUSION: Our results support that discoid excision is safe and associated with good fertility outcomes. Whether first-line surgery using discoid excision is superior to first-line ART remains to be determined.
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Neoplasias Colorretais , Endometriose , Infertilidade Feminina , Doenças Retais , Gravidez , Feminino , Humanos , Endometriose/complicações , Endometriose/cirurgia , Doenças Retais/cirurgia , Doenças Retais/complicações , Fertilidade , Infertilidade Feminina/cirurgia , Infertilidade Feminina/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Colorretais/complicaçõesRESUMO
OBJECTIVE: Patients with superficial peritoneal endometriosis (SPE) present with symptoms suggestive of endometriosis but clinical and imaging exams are inconclusive. Consequently, laparoscopy is usually necessary to confirm diagnosis. The present study aimed to evaluate the accuracy of microRNAs (miRNAs) to diagnose patients with SPE from the ENDOmiARN cohort STUDY DESIGN: This prospective study (NCT04728152) included 200 saliva samples obtained between January and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy and/or MRI to confirm the presence of endometriosis. Among the patients with endometriosis, two groups were defined: an SPE phenotype group of patients with peritoneal lesions only, and a non-SPE control group of patients with other endometriosis phenotypes (endometrioma and/or deep endometriosis). Data analysis consisted of two parts: (i) identification of a set of miRNA biomarkers using next-generation sequencing (NGS), and (ii) development of a saliva-based miRNA signature for the SPE phenotype in patients with endometriosis based on a Random Forest (RF) model. RESULTS: Among the 153 patients with confirmed endometriosis, 10.5 % (n = 16) had an SPE phenotype. Of the 2633 known miRNAs, the feature selection method generated a signature of 89 miRNAs of the SPE phenotype. After validation, the best model, representing the most accurate signature had a 100 % sensitivity, specificity, and AUC. CONCLUSION: This signature could constitute a new diagnostic strategy to detect the SPE phenotype based on a simple biological test and render diagnostic laparoscopy obsolete. PRéCIS: We generated a saliva-based signature to identify patients with superficial peritoneal endometriosis which is the most challenging form of endometriosis to diagnose and which is often either misdiagnosed or requires invasive laparoscopy.
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Endometriose , MicroRNAs , Fenótipo , Saliva , Humanos , Feminino , Endometriose/diagnóstico , Endometriose/genética , Adulto , MicroRNAs/metabolismo , MicroRNAs/análise , MicroRNAs/genética , Saliva/química , Estudos Prospectivos , Doenças Peritoneais/diagnóstico , Doenças Peritoneais/genética , Doenças Peritoneais/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análise , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: In contrast to miRNA expression, little attention has been given to piwiRNA (piRNA) expression among endometriosis patients. The aim of the present study was to explore the human piRNAome and to investigate a potential piRNA saliva-based diagnostic signature for endometriosis. METHODS: Data from the prospective "ENDOmiRNA" study (ClinicalTrials.gov Identifier: NCT04728152) were used. Saliva samples from 200 patients were analyzed in order to evaluate human piRNA expression using the piRNA bank. Next Generation Sequencing (NGS), barcoding of unique molecular identifiers and both Artificial Intelligence (AI) and machine learning (ML) were used. For each piRNA, sensitivity, specificity, and ROC AUC values were calculated for the diagnosis of endometriosis. RESULTS: 201 piRNAs were identified, none had an AUC ≥ 0.70, and only three piRNAs (piR-004153, piR001918, piR-020401) had an AUC between ≥ 0.6 and < 0.70. Seven were differentially expressed: piR-004153, piR-001918, piR-020401, piR-012864, piR-017716, piR-020326 and piR-016904. The respective correlation and accuracy to diagnose endometriosis according to the F1-score, sensitivity, specificity, and AUC ranged from 0 to 0.862 %, 0-0.961 %, 0.085-1, and 0.425-0.618. A correlation was observed between the patients' age (≥35 years) and piR-004153 (p = 0.002) and piR-017716 (p = 0.030). Among the 201 piRNAs, four were differentially expressed in patients with and without hormonal treatment: piR-004153 (p = 0.015), piR-020401 (p = 0.001), piR-012864 (p = 0.036) and piR-017716 (p = 0.009). CONCLUSION: Our results support the link between piRNAs and endometriosis physiopathology and establish its utility as a potential diagnostic biomarker using saliva samples. Per se, piRNA expression should be analyzed along with the clinical status of a patient.
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Endometriose , RNA de Interação com Piwi , Feminino , Humanos , Adulto , RNA Interferente Pequeno/genética , Endometriose/diagnóstico , Endometriose/genética , Inteligência Artificial , Estudos Prospectivos , BiomarcadoresRESUMO
Breast cancer in women is the second most common cancer and the fifth leading cause of cancer death worldwide. Although earlier diagnosis and detection of breast cancer has resulted in lower mortality rates, further advances in prevention, detection, and treatment are needed to improve outcomes and survival for women with breast cancer as well as to offer a personalized therapeutic approach. It is now well-established that non-coding RNAs (ncRNAs) represent 98% of the transcriptome but in-depth knowledge about their involvement in the regulation of gene expression is lacking. A growing body of research indicates that ncRNAs are essential for tumorigenesis by regulating the expression of tumour-related genes. In this review, we focus on their implication in breast cancer genesis but also report the latest knowledge of their theragnostic and therapeutic role. We highlight the need for accurate quantification of circulating ncRNAs which is determinant to develop reliable biomarkers. Further studies are mandatory to finally enter the era of personalized medicine for women with breast cancer.
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Endometriosis, characterized by endometrial-like tissue outside the uterus, is thought to affect 2-10% of women of reproductive age: representing about 190 million women worldwide. Numerous studies have evaluated the diagnostic value of blood biomarkers but with disappointing results. Thus, the gold standard for diagnosing endometriosis remains laparoscopy. We performed a prospective trial, the ENDO-miRNA study, using both Artificial Intelligence (AI) and Machine Learning (ML), to analyze the current human miRNome to differentiate between patients with and without endometriosis, and to develop a blood-based microRNA (miRNA) diagnostic signature for endometriosis. Here, we present the first blood-based diagnostic signature obtained from a combination of two robust and disruptive technologies merging the intrinsic quality of miRNAs to condense the endometriosis phenotype (and its heterogeneity) with the modeling power of AI. The most accurate signature provides a sensitivity, specificity, and Area Under the Curve (AUC) of 96.8%, 100%, and 98.4%, respectively, and is sufficiently robust and reproducible to replace the gold standard of diagnostic surgery. Such a diagnostic approach for this debilitating disorder could impact recommendations from national and international learned societies.
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Endometriose , MicroRNAs , Inteligência Artificial , Biomarcadores , Endometriose/genética , Endométrio , Feminino , Humanos , Estudos ProspectivosRESUMO
The pathophysiology of endometriosis remains poorly understood. The aim of the present study was to investigate functions and pathways associated with the various miRNAs differentially expressed in patients with endometriosis. Plasma samples of the 200 patients from the prospective "ENDO-miRNA" study were analyzed and all known human miRNAs were sequenced. For each miRNA, sensitivity, specificity, and ROC AUC values were calculated for the diagnosis of endometriosis. miRNAs with an AUC ≥ 0.6 were selected for further analysis. A comprehensive review of recent articles from the PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases was performed to identify functions and pathways associated with the selected miRNAs. In total, 2633 miRNAs were found in the patients with endometriosis. Among the 57 miRNAs with an AUC ≥ 0.6: 20 had never been reported before; one (miR-124-3p) had previously been observed in endometriosis; and the remaining 36 had been reported in benign and malignant disorders. miR-124-3p is involved in ectopic endometrial cell proliferation and invasion and plays a role in the following pathways: mTOR, STAT3, PI3K/Akt, NF-κB, ERK, PLGF-ROS, FGF2-FGFR, MAPK, GSK3B/ß-catenin. Most of the remaining 36 miRNAs are involved in carcinogenesis through cell proliferation, apoptosis, and invasion. The three main pathways involved are Wnt/ß-catenin, PI3K/Akt, and NF-KB. Our results provide evidence of the relation between the miRNA profiles of patients with endometriosis and various signaling pathways implicated in its pathophysiology.
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OBJECTIVE: Parametrial involvement (PI) in endometriosis is poorly defined resulting in an underestimation of its impact during surgical excision. The aim of our study was to assess the surgical complications associated with parametrectomy during surgery for endometriosis. Our secondary objective was to compare the surgical complications rates of a parametrectomy to the excision of other deep pelvic endometriotic locations. STUDY DESIGN: Patients who underwent surgery for deep pelvic endometriosis from 2013 to 2018 in a French referral center were retrospectively included. Surgical complications were assessed according to whether a parametrectomy had been performed. The extent of surgery (colpectomy, torus, utero-sacral (USL) and/or rectal resection) was also assessed. Voiding dysfunction was defined as the need for self-catheterization ≥1 month and intra and postoperative complications were graded using the Clavien-Dindo classification (CDC). RESULTS: We included 753 patients: 285 (37.8 %) with PI. Patients with PI had higher ASRM scores and more extensive surgery than those without. These patients also had higher rates of voiding dysfunctions (17.5 % versus 8.98 %, p < 0.01), and postoperative complications (44.6 % versus 24.6 %, p < 0.01), including major complications (CDC 3-4) (14.7 % vs 8.5 %, p = 0.01). The extent of the surgical resection of endometriosis was strongly associated with surgical complications after multivariable analysis, and the addition of a parametrectomy during surgery greatly increased rates of adverse postoperative events. Voiding dysfunction was frequent in women with combined resection of the torus, utero-sacral ligaments, parametrium and vagina (adjusted OR = 37.28, 95 %CI = 6.84-203.11, p < 0.01, reference: resection of the USL). CONCLUSION: Parametrectomy significantly impacts postoperative complications in patients undergoing surgery for endometriosis.
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Endometriose , Laparoscopia , Doenças Retais , Endometriose/complicações , Endometriose/cirurgia , Feminino , Humanos , Laparoscopia/métodos , Peritônio , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Prognóstico , Doenças Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Endometriosis-a systemic and chronic condition occurring in women of childbearing age-is a highly enigmatic disease with unresolved questions. While multiple biomarkers, genomic analysis, questionnaires, and imaging techniques have been advocated as screening and triage tests for endometriosis to replace diagnostic laparoscopy, none have been implemented routinely in clinical practice. We investigated the use of machine learning algorithms (MLA) in the diagnosis and screening of endometriosis based on 16 key clinical and patient-based symptom features. The sensitivity, specificity, F1-score and AUCs of the MLA to diagnose endometriosis in the training and validation sets varied from 0.82 to 1, 0-0.8, 0-0.88, 0.5-0.89, and from 0.91 to 0.95, 0.66-0.92, 0.77-0.92, respectively. Our data suggest that MLA could be a promising screening test for general practitioners, gynecologists, and other front-line health care providers. Introducing MLA in this setting represents a paradigm change in clinical practice as it could replace diagnostic laparoscopy. Furthermore, this patient-based screening tool empowers patients with endometriosis to self-identify potential symptoms and initiate dialogue with physicians about diagnosis and treatment, and hence contribute to shared decision making.
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Endometriose , Feminino , HumanosRESUMO
The aim of our study was to describe the bioinformatics approach to analyze miRNome with Next Generation Sequencing (NGS) of 200 plasma samples from patients with and without endometriosis. Patients were prospectively included in the ENDO-miRNA study that selected patients with pelvic pain suggestive of endometriosis. miRNA sequencing was performed using an Novaseq6000 sequencer (Illumina, San Diego, CA, USA). Small RNA-seq of 200 plasma samples yielded ~4228 M raw sequencing reads. A total of 2633 miRNAs were found differentially expressed. Among them, 8.6% (n = 229) were up- or downregulated. For these 229 miRNAs, the F1-score, sensitivity, specificity, and AUC ranged from 0-88.2%, 0-99.4%, 4.3-100%, and 41.5-68%, respectively. Utilizing the combined bioinformatic and NGS approach, a specific and broad panel of miRNAs was detected as being potentially suitable for building a blood signature of endometriosis.
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BACKGROUND: Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis. METHODS: We performed a prospective ENDO-miRNA study involving 200 saliva samples obtained from 200 women with chronic pelvic pain suggestive of endometriosis collected between January and June 2021. The study consisted of two parts: (i) identification of a biomarker based on genome-wide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) and (ii) development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a Random Forest algorithm. RESULTS: Among the 200 patients, 76.5% (n = 153) were diagnosed with endometriosis and 23.5% (n = 47) without (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). Quantification of the filtered reads and identification of known miRNAs yielded ~190 M sequences that were mapped to 2561 known miRNAs. Of the 2561 known miRNAs, the feature selection with Random Forest algorithm generated after internally cross validation a saliva signature of endometriosis composed of 109 miRNAs. The respective sensitivity, specificity, and AUC for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%. CONCLUSIONS: The ENDO-miRNA study is the first prospective study to report a saliva-based diagnostic miRNA signature for endometriosis. This could contribute to improving early diagnosis by means of a non-invasive tool easily available in any healthcare system.
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INTRODUCTION: Triple-negative (TN) breast cancer represents one third of pregnancy-associated breast cancers (PABC). The aims of the current study were to describe oncological and obstetrical outcomes of patients with TN-PABC and to compare their prognosis with TN-non-PABC patients using a propensity score. MATERIALS AND METHODS: Between January 2005 and December 2020, data of patients with histologically proven TN-PABC were collected and compared with data of TN-non-PABC patients under the age of 46 years diagnosed during the same period using a propensity score (PS). RESULTS: After PS matching (tumor size and lymph node involvement),there were 59 patients in each group. The median follow-up was 14 months (IQR 4.8-40.1) for the TN-PABC group and 60 months (IQR 30.7-101.4) for the TN-non-PABC group. Eight recurrences occurred in the TN-PABC group and 10 in the TN-non-PABC group (adjusted OR (AOR) = 0.60 (0.21-1.60), HR (Cox adjusted model- AHR) = 1.25 (0.53-2.94)). Two patients died in the TN-PABC group, and six in the TN-non-PABC group with an AOR = 0.23 (0.03-1.01) and an AHR = 0.58 (0.12-2.69). All the patients diagnosed during the second (n = 17) and third trimesters (n = 28) continued their pregnancies, with a median term at delivery of 38 WG (IQR 36-39). All patients gave birth to healthy newborns. CONCLUSION: Although the TN subtype is associated with poor prognosis in pregnant patients due to advanced stage at diagnosis and high lymph node involvement, our PS-matched case-control study showed that pregnancy per se does not worsen the prognosis in terms of recurrence-free and overall survival.
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Neoplasias da Mama , Complicações Neoplásicas na Gravidez , Neoplasias de Mama Triplo Negativas , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Gravidez , Prognóstico , Pontuação de PropensãoRESUMO
OBJECTIVES: To study the measurement properties, the responsiveness and the minimal clinically important difference of the ENDOPAIN-4D: a new questionnaire for assessing pain in endometriosis. METHODS: A prospective, observational, multicentre study was conducted including all women ≥18 years consulting for symptomatic proven endometriosis between 1 January 2017 and 30 June 2018 and volunteering to participate. Each patient had to answer a new self-administered patient-reported outcome (PRO) questionnaires (the ENDOPAIN-4D) at inclusion (T0) and 12 months after medical or surgical treatment (T1). Criteria defined by COSMIN were used to validate the questionnaire's measurement properties. The minimal clinically important difference was estimated by the anchor-based method. RESULTS: The study included 199 women. The ENDOPAIN-4D score had a four dimensional structure with good internal consistency (measured by Cronbach α): (I) pain-related disability (α = 0.79), (II) painful bowel symptoms (α = 0.80), (III) dyspareunia (α = 0.83), and (IV) painful urinary tract symptoms (α = 0.77). They produced four subscores that can be summed to obtain a single score (α = 0.61). The ENDOPAIN-4D total score ranged from 0 to 94.00 (mean ± SD: 46.7 ± 22). The total score was significantly correlated with the PROs used in endometriosis. Sensitivity to change was good with large effect sizes (ES) (mean of the differences: 36.3 p = 1.8 10-7, ES 0.76). The minimal clinically important difference of the global score was determined to be 10.9. CONCLUSIONS: The ENDOPAIN-4D questionnaire is easy to use, valid, and effective in assessing patient reported pain symptoms in women treated for endometriosis. This new instrument can be used as the primary outcome for future clinical trials and as a tool for routine patient follow-up.
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Fibroids, which are benign smooth-muscle tumors of clonal origin, are the most common gynecologic tumors occurring in about 20 to 25 % of women over 30 years of age. The most frequent symptoms are pelvic pain and heavy menstrual bleeding resulting in anemia. The role of fibroids in infertility remains debated but probably mostly related to submucosal location due to implantation impairment. Although most women are asymptomatic (80%), fibroids can have a considerable impact on quality of life. Considering this impact and the cost associated with their management, treatment of fibroids is a public health concern. Treatment options for symptomatic fibroids include medical, surgical and alternatives techniques. Medical management is mainly based on the use of progestogens, antifibrinolytics agents, non-steroidal anti-inflammatory drugs, Gonadotropin-releasing hormone analogs selective progesterone receptor modulators. Surgical management includes myomectomy (hysteroscopic, laparoscopic, minilaparoscopic or laparotomic) and hysterectomy. The choice of surgery depends on several factors: the number, topography and size of myomas, the age of the patient and her desire for fertility, treatment history and her desire to keep the uterus. Alternatives techniques to surgery are mainly based on the uterine artery embolization. The aim of this article is to provide evidence based recommendations for the management of uterine fibroids.