Saliva-based microRNA diagnostic signature for the superficial peritoneal endometriosis phenotype.

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.

New class of RNA biomarker for endometriosis diagnosis: The potential of salivary piRNA expression.

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.

Insight on Non-Coding RNAs from Biofluids in Ovarian Tumors.

Ovarian tumors are the most frequent adnexal mass, raising diagnostic and therapeutic issues linked to a large spectrum of tumors, with a continuum from benign to malignant. Thus far, none of the available diagnostic tools have proven efficient in deciding strategy, and no consensus exists on the best strategy between "single test", "dual testing", "sequential testing", "multiple testing options" and "no testing". In addition, there is a need for prognostic tools such as biological markers of recurrence and theragnostic tools to detect women not responding to chemotherapy in order to adapt therapies. Non-coding RNAs are classified as small or long based on their nucleotide count. Non-coding RNAs have multiple biological functions such as a role in tumorigenesis, gene regulation and genome protection. These ncRNAs emerge as new potential tools to differentiate benign from malignant tumors and to evaluate prognostic and theragnostic factors. In the specific setting of ovarian tumors, the goal of the present work is to offer an insight into the contribution of biofluid non-coding RNAs (ncRNA) expression.

Endometriosis-associated infertility diagnosis based on saliva microRNA signatures.

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% (n = 36) were infertile and 76% (n = 117) were fertile. Small RNA-sequencing of the 153 saliva samples yielded approximately 3712 M raw sequencing reads (from ∼13.7 M to ∼39.3 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.

Validation of a Salivary miRNA Signature of Endometriosis - Interim Data.

Salivary miRNA Signature of EndometriosisThis interim analysis of the prospective, multicenter, external validation ENDOmiRNA Saliva Test study, confirms the diagnostic performance and reproducibility of the saliva miRNA signature for endometriosis. At a population prevalence of ∼80%, the miRNA signature had a sensitivity of 96.2%, specificity of 95.1%, and area under the curve of 0.96.

Endometriosis Associated-miRNome Analysis of Blood Samples: A Prospective Study.

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.

Salivary MicroRNA Signature for Diagnosis of Endometriosis.

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.

Machine learning algorithms as new screening approach for patients with endometriosis.

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.

Prognostic relevance of celiac lymph node involvement in ovarian cancer.

OBJECTIVE: The aim of the study was to report on the oncologic outcome of the disease spread to celiac lymph nodes (CLNs) in advanced-stage ovarian cancer patients. METHODS: All patients who had CLN resection as part of their cytoreductive surgery for epithelial ovarian, fallopian, or primary peritoneal cancer were identified. Patient demographic data with particular emphasis on operative records to detail the extent and distribution of the disease spread, lymphadenectomy procedures, pathologic data, and follow-up data were included. RESULTS: The median follow-up was 26.3 months. The median overall survival values in the group with positive CLNs and in the group with negative CLNs were 26.9 months and 40.04 months, respectively. The median progression-free survival values in the group with metastatic CLNs and in the group with negative CLNs were 8.8 months and 20.24 months, respectively (P = 0.053). Positive CLNs were associated with progression during or within 6 months after the completion of chemotherapy (P = 0.0044). Tumor burden and extensive disease distribution were significantly associated with poor progression-free survival, short-term progression, and overall survival. In multivariate analysis, only the CLN status was independently associated with short-term progression. CONCLUSIONS: Disease in the CLN is a marker of disease severity, which is associated to a high-risk group of patients with presumed adverse tumor biology, increased risk of lymph node progression, and worst oncologic outcome.

Fertility-preserving surgical procedures, techniques.

As a result of the trend toward late childbearing, fertility preservation has become a major issue in young women with gynaecological cancer. Fertility-sparing treatments have been successfully attempted in selected cases of cervical, endometrial and ovarian cancer, and gynaecologists should be familiar with fertility-preserving options in women with gynaecological malignancies. Options to preserve fertility include shielding to reduce radiation damage, fertility preservation when undergoing cytotoxic treatments, cryopreservation, assisted reproduction techniques, and fertility-sparing surgical procedures. Radical vaginal trachelectomy with laparoscopic lymphadenectomy is an oncologically safe, fertility-preserving procedure. It has been accepted worldwide as a surgical treatment of small early stage cervical cancers. Selected cases of early stage ovarian cancer can be treated by unilateral salpingo-ophorectomy and surgical staging. Hysteroscopic resection and progesterone treatment are used in young women who have endometrial cancer to maintain fertility and avoid surgical menopause. Appropriate patient selection, and careful oncologic, psychologic, reproductive and obstetric counselling, is mandatory.

Uterine perforation by a cystoperitoneal shunt, an unusual cause of recurrent vaginal discharge.

BACKGROUND: We describe the first reported case of uterine perforation by a cystoperitoneal shunt. The mechanism of this unusual complication is unclear. CASE: A 17-year-old patient had a cystoperitoneal shunt for a porencephalic cyst. She presented with recurrent watery vaginal discharge. A pelvic ultrasound examination showed that the uterus had been perforated by the distal tip of the shunt. The cystoperitoneal shunt was converted to a ventriculo-atrial shunt, and the vaginal discharge subsequently resolved. CONCLUSION: The appearance of light and clear vaginal discharge in a patient with a cystoperitoneal shunt raises the possibility of uterine perforation. This can be confirmed by ultrasound and analysis of the discharge. Removal of the shunt leads to spontaneous closure of the uterine defect.

[Ovarian preservation during treatment of early stage endometrial cancer]. / Place de la préservation ovarienne dans le traitement des carcinomes endométriaux de stades précoces.

Endometrial cancer staging is based on surgery. No matter the age of the patient, the surgical staging includes at least a total hysterectomy with bilateral salpingo-oophorectomy. Twenty to 25% of the patients diagnosed with endometrial cancer are younger than 45  years. Although some discrepancies among series may be observed, in this population, endometrial cancers are mainly of lower grade, confined to the uterus (without ovarian involvement) and of better prognosis compared to older patients. The impact of premature menopause on the quality of life, cardiovascular and bone systems should not be neglected. This raises the issue of the systematic bilateral oophorectomy legitimacy while staging endometrial cancer staging in young patient. Considering the literature, eligibility criteria to ovarian preservation in endometrial cancer would be: young patients, low-grade endometrioid tumor, disease limited to the uterus (absence of any extrauterine disease). The risk of occult ovarian lesions, either synchronous or metastatic, would than be close to 1%. The effects of residual hormonal stimulation are considered low. Nevertheless, bilateral oophorectomy should remain the standard. Oophorectomy preservation in endometrial cancer should be considered as an exception, and proposed as an individualized plan of care for patients with strict eligibility criteria.

Pure flat epithelial atypia (DIN 1a) on core needle biopsy: study of 60 biopsies with follow-up surgical excision.

Flat epithelial atypia (FEA) is recognized as a precursor of breast cancer and its management (surgical excision or intensive follow-up) remains unclear after diagnosis on core needle biopsy (CNB). The aim of this study was to determine the underestimation rate of pure FEA on CNB and clinical, radiological, and pathological factors of underestimation. 4,062 CNBs from 5 breast cancer centers, performed over a 5-year period, were evaluated. A CNB diagnosis of pure FEA was made in 60 cases (1.5%) (the presence of atypical ductal hyperplasia, lobular neoplasia, radial scars, phyllodes tumor, papillary lesions, ductal carcinoma in situ or invasive carcinoma at CNB were exclusion criteria), and subsequent surgical excision was systematically performed. The histological diagnosis was retrospectively reviewed using standardized criteria and the precise terminology of the World Health Organization by two pathologist physicians. At surgical excision, 6 (10%) ductal carcinoma in situ and 2 (3%) invasive carcinoma were diagnosed. The total underestimation rate was 13%. FEA was associated with atypical ductal hyperplasia in 10 (17%) cases and with lobular neoplasia in 2 (3%) at final pathology. Residual FEA was found in 14 (23%) cases. No clinical, radiological or pathological factors were significantly associated with underestimation. Our data highlight the importance of recognizing and diagnosing FEA in core needle biopsies. Thus, the presence of FEA on CNB, even in isolation, warrants follow-up excision.

Successful expectant management for a cornual heterotopic pregnancy.

OBJECTIVE: To report the obstetric outcome after expectant management for a right cornual heterotopic pregnancy. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 33-year-old salpingectomized woman with an 8-year history of primary infertility who conceived after in utero transfer of two embryos obtained by in vitro fertilization. INTERVENTION(S): Expectant management and close ultrasonographic and clinical monitoring. MAIN OUTCOME MEASURE(S): Obstetric outcome. RESULT(S): The intrauterine pregnancy proceeded unremarkably. A caesarean section was performed for dystocia and allowed the delivery of a healthy 4170 g male infant. The examination of the uterus showed a prerupture of the right uterine horn. CONCLUSION(S): Expectant management for cornual heterotopic pregnancy could be considered a successful option in a symptom-free patient where the ectopic embryo has a limited craniocaudal length with no cardiac activity. Our case also suggests that elective cesarean section could be the optimal mode of delivery for rare cases of successful management for cornual heterotopic pregnancy, regardless of the therapeutic option chosen for the cornual pregnancy, due to the theoretical increase risk of uterine rupture during labor.

Rupture of an aneurysm of the ovarian artery following delivery and endovascular treatment.

We report a case of spontaneous rupture of an ovarian artery aneurysm, 5 days after delivery. Severe abdominal pain justified a computed tomography scan, which revealed a massive retroperitoneal hematoma. Arteriography showed the rupture of an ovarian artery aneurysm that was successfully embolized using microcoils.

Incidental finding of an intrauterine device in the sigmoid colon.

BACKGROUND: Translocation of an intrauterine device (IUD) to the sigmoid colon lumen is an extremely rare presentation of an ectopic IUD that usually results in fever and gastrointestinal symptoms. We report the exceptional case of an asymptomatic IUD translocation to the sigmoid colon lumen secondary to uterine perforation. CASE REPORT: A CT-scan was carried out during the follow-up of a 53-year-old woman with a metastatic epidermoid carcinoma of the tongue evolving over the previous eight years. It incidentally revealed the presence of an IUD in the sigmoid colon lumen. The patient being completely asymptomatic and at the terminal stage of her disease, removal of the device by means of a surgical or endoscopic procedure was not attempted. The patient died four months later due to lung cancer; during that period of time the IUD located in the colon remained asymptomatic. CONCLUSION: Asymptomatic migration of IUD to the sigmoid colon lumen can occur. Except when the patient's condition does not allow it, as in the case reported, removal of the IUD is indicated because of the risk of fistula formation and colon perforation with a high ensuing morbidity. This case report highlights the need for follow-up of patients wearing an IUD.

[A case report of stromal tumor in the ligamentum teres hepatis]. / Tumeur stromale du ligament rond hépatique. A propos d'un cas.

This case report relates to a 73-year old man presenting a large susmesocolic abdominal tumor whose analysis demonstrated to be a stromal tumour of the ligamentum teres hepatis.