Radiomic study of antenatal prediction of severe placenta accreta spectrum from MR imaging.

OBJECTIVE: We previously demonstrated the potential of radiomics for prediction of severe histological Placenta Accreta Spectrum (PAS) subtypes using T2-weighted MRI. We aim is to validate our model using an additional dataset. Secondly, we explore whether performance is improved using a new approach to develop a new multivariate radiomics model. METHODS: Multi-centre retrospective analysis conducted between 2018-2023. Inclusion criteria: MRI performed for suspicion of PAS from ultrasound, clinical findings of PAS at laparotomy and/or histopathological confirmation. Radiomic features were extracted from T2-weighted MRI. The previous multivariate model was validated. Secondly, a 5-radiomic feature random forest classifier was selected from a randomised feature selection scheme to predict invasive placenta increta PAS cases. Prediction performance was assessed based on several metrics including Area Under the Curve (AUC) of the receiver operating characteristic curve (ROC), sensitivity and specificity. RESULTS: We present 100 women (mean age 34.6 (±3.9) with PAS, 64 of whom had placenta increta. Firstly, we validated the previous multivariate model and found a Support Vector Machine classifier had a sensitivity of 0.620 (95% CI: 0.068; 1.0), specificity of 0.619 (95% CI: 0.059; 1.0), an AUC of 0.671 (95% CI: 0.440; 0.922) and accuracy of 0.602 (95% CI: 0.353; 0.817) for predicting placenta increta. From the new multivariate model, the best 5-feature subset selected via the random subset feature selection scheme comprised of 4 radiomic features and 1 clinical variable (number of previous caesareans). This clinical-radiomic model achieved an AUC of 0.713 (95% CI: 0.551; 0.854), accuracy of 0.695 (95% CI 0.563; 0.793), sensitivity of 0.843 (95% CI 0.682; 0.990) and specificity of 0.447 (95% CI 0.167; 0.667). CONCLUSION: We validated our previous model and present a new multivariate radiomic model for prediction of severe placenta increta from a well-defined, cohort of PAS cases. ADVANCES IN KNOWLEDGE: Radiomic features demonstrate good predictive potential for identifying placenta increta. This suggests radiomics may be a useful adjunct to clinicians caring for women with this high-risk pregnancy condition.

Landscape of HER2-low breast cancer: Insights from a six-year study on prevalence and clinicopathological characteristics.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+/2+ in immunohistochemistry (IHC) and absence of ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2-low breast cancer to novel anti-HER2 antibody-drug-conjugates. Data on characteristics of HER2-low breast cancer subtype is limited. Real-world data from the Anatomic Pathology Department of Hotel-Dieu de France, spanning 2017-2023, was retrospectively collected. HER2-positive patients were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Clinicopathological characteristics between the groups were compared using a Chi-Squared test. Out of 1195 patients, we observed 341 (28.5 %) HER2-low breast cancers cases. HER2-positive breast cancer cases (n = 178; 14.9 %) were excluded. There was no significant difference in age and sex between HER2-low and HER2-zero group (p = 0.33 and 0.79, respectively). HER2-low breast cancer was associated with positive estrogen receptor status and positive progesterone receptor status (p < 0.001 and p = 0.01, respectively). Ductal adenocarcinomas were more commonly observed in HER2-low group (p < 0.001). When stratified by hormone (HR) status, 87.4 % of patients had HR-positive status and 12.6 % were HR-negative. Among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (25%vs.10 %, p = 0.04). This study showed that HER2-low is distinct from HER2-zero and is common among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

The Lebanese percreta group: A retrospective cohort study of both radical and conservative management outcomes of abnormally invasive placenta.

OBJECTIVE: The aim of the present study was to illustrate the outcomes of abnormally invasive placenta (AIP) cases managed in three leading centers in Lebanon. METHODS: We conducted a retrospective multicenter cohort study. Patients managed conservatively (cesarean delivery with successful placental separation) or radically (cesarean hysterectomy) were included in the study. Data included patient characteristics, surgical outcomes (blood loss, operative time, transfusion, partial bladder resection), maternal outcomes (death, length of stay, ICU admission, postoperative hemoglobin level) and neonatal outcomes (Apgar score, neonatal weight, admission to neonatal intensive care unit, neonatal death). RESULTS: The study included 189 patients. In the radical treatment subgroup (141/189), patients were para 3 and delivered at 34 4/7 weeks in average, bled 1.5 L and were transfused with three packed red blood cells, with operative time averaging 160 min. A total of 36% were admitted to the ICU and patients stayed on average for 1 week despite partial bladder resection in 19% of cases. Unscheduled radical delivery occurred at a lower gestational age, was associated with more blood loss, higher rate and volume of transfusion, and risk of maternal and neonatal death. In addition, patients delivered in an unscheduled fashion experienced higher rates of partial bladder resection and longer interventions. In the conservative treatment subgroup, on average patients were para 2 and delivered at 36 weeks, bled 800 mL on average with low rates of transfusion (35%) and ICU admission (22.9%). With regard to neonatal outcomes, the average neonatal birth weight was 2.4 kg in the radical subgroup and 2.5 kg in the conservative subgroup. Neonatal death occurred in 5.4% of cases requiring radical management while it occurred in 2% of patients treated conservatively. CONCLUSION: Through their multidisciplinary approach, the three centers demonstrated that management of AIP in Lebanon has led to excellent outcomes with no maternal mortality occurring in scheduled radical treatment. By comparison of the three leading centers, pitfalls in each center were identified and addressed.

Radiomics-based prediction of FIGO grade for placenta accreta spectrum.

BACKGROUND: Placenta accreta spectrum (PAS) is a rare, life-threatening complication of pregnancy. Predicting PAS severity is critical to individualise care planning for the birth. We aim to explore whether radiomic analysis of T2-weighted magnetic resonance imaging (MRI) can predict severe cases by distinguishing between histopathological subtypes antenatally. METHODS: This was a bi-centre retrospective analysis of a prospective cohort study conducted between 2018 and 2022. Women who underwent MRI during pregnancy and had histological confirmation of PAS were included. Radiomic features were extracted from T2-weighted images. Univariate regression and multivariate analyses were performed to build predictive models to differentiate between non-invasive (International Federation of Gynecology and Obstetrics [FIGO] grade 1 or 2) and invasive (FIGO grade 3) PAS using R software. Prediction performance was assessed based on several metrics including sensitivity, specificity, accuracy and area under the curve (AUC) at receiver operating characteristic analysis. RESULTS: Forty-one women met the inclusion criteria. At univariate analysis, 0.64 sensitivity (95% confidence interval [CI] 0.0-1.00), specificity 0.93 (0.38-1.0), 0.58 accuracy (0.37-0.78) and 0.77 AUC (0.56-.097) was achieved for predicting severe FIGO grade 3 PAS. Using a multivariate approach, a support vector machine model yielded 0.30 sensitivity (95% CI 0.18-1.0]), 0.74 specificity (0.38-1.00), 0.58 accuracy (0.40-0.82), and 0.53 AUC (0.40-0.85). CONCLUSION: Our results demonstrate a predictive potential of this machine learning pipeline for classifying severe PAS cases. RELEVANCE STATEMENT: This study demonstrates the potential use of radiomics from MR images to identify severe cases of placenta accreta spectrum antenatally. KEY POINTS: • Identifying severe cases of placenta accreta spectrum from imaging is challenging. • We present a methodological approach for radiomics-based prediction of placenta accreta. • We report certain radiomic features are able to predict severe PAS subtypes. • Identifying severe PAS subtypes ensures safe and individualised care planning for birth.

Consensus on the management of platinum-sensitive high-grade serous epithelial ovarian cancer in Lebanon.

Ovarian cancer is the most lethal gynecologic cancer. The high grade serous epithelial (HGSE) subtype is the most aggressive and it often presents at advanced stages, while screening programs have not proven beneficial. Management of the advanced stages (FIGO III and IV), which constitute the majority of diagnoses, usually consists of platinum-based chemotherapy and cytoreductive surgery (primary or interval) followed by maintenance therapy. Currently, the standard-of-care for advanced newly diagnosed HGSE ovarian cancer, as per international medical societies, starts with upfront cytoreductive surgery, followed by platinum-based chemotherapy (mostly carboplatin and paclitaxel) and/or anti-angiogenic agent bevacizumab, then maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor with/without/or bevacizumab (continued). PARP inhibitor use depends on the patient's genetic signature, mainly the breast cancer gene (BRCA) mutation and the homologous recombination deficiency (HRD) status. Therefore, genetic testing is recommended at diagnosis to inform treatment and prognosis. In line with the evolving standard-of-care for ovarian cancer, a panel of experts in treating advanced ovarian cancer convened to lay down practical recommendations on the management of advanced ovarian cancer in Lebanon; since the currently applicable guidelines by the Lebanese Ministry of Public Health for cancer treatment have not been updated yet to reflect the treatment paradigm shift brought upon by the development and approval of PARP inhibitors. The current work reviews the leading clinical trials on PARP inhibitors (as maintenance for newly diagnosed advanced and platinum-sensitive relapsed ovarian cancer), presents international recommendations, and proposes treatment algorithms for optimal local practice.

Genetic profile of borderline ovarian tumors in the Lebanese population by whole-exome sequencing.

OBJECTIVE: To assess the molecular profile of borderline ovarian tumors (BOT) in the Lebanese population by whole-exome sequencing and to correlate the results with the patients' clinical profiles. METHODS: We included in this retrospective study 33 tumors belonging to 32 Lebanese women presenting with BOT, diagnosed at Hôtel Dieu de France. A total of 234 genes involved in different germinal and somatic types of cancer were analyzed using next-generation sequencing. RESULTS: Molecular analysis of these tumors allowed us to detect mutations in genes involved in the mitogen-activated protein kinase cascade in 57.58% of BOT and to identify variants affecting the DNA repair mechanism in 63.89% of samples. Furthermore, our initial analysis revealed an association between defects in DNA double-strand break repair and the occurrence of mucinous BOT, in 75% of the cases. CONCLUSION: This study reports the molecular profiles of BOT in the Lebanese population and compares them to the literature. This is the first study associating the DNA repair pathway to BOT.

HSP27 modulates tumoural immune evasion by enhancing STAT3-mediated upregulation of PD-L1 and NLRC5 in ovarian cancer.

Multiple preclinical studies have demonstrated that the addition of hyperthermia (HT) to immunotherapy could enhance tumour immunogenicity and stimulate an antitumour immune response, primarily via heat shock proteins (HSPs). However, antitumour immune responses are often impeded by immune evasion mechanisms, such as the overexpression of programmed death-ligand1 (PD-L1) and the loss of major histocompatibility complex class 1 (MHC-1) expression. In this context, we sought to investigate the effect of HT on PD-L1 and NOD-like receptor family CARD domain containing 5 (NLRC5) identified as the key transcriptional activator of MHC-1 genes, and their interaction in ovarian cancer. A coculture of ovarian cancer cell lines (IGROV1 and SKOV3) with peripheral blood mononuclear cells was set up. Then, culture media conditioned with IGROV1 or SKOV3 subjected to HT was tested on untreated cell cultures. Knocking down heat shock protein B1 (HSPB1 or HSP27), heat shock protein A1 (HSPA1 or HSP70), and pharmacological inhibition of STAT3 phosphorylation were performed. Subsequently, we measured expression levels of PD-L1, NLRC5, and proinflammatory cytokines. The correlation between PD-L1 and NLRC5 expression in ovarian cancer was evaluated using the Cancer Genome Atlas database. We found that HT produces a concomitant decrease in PD-L1 and NLRC5 expression in coculture. Notably, however, the conditioned media by heat-shocked cells increases their expression. HSP27 knockdown can reverse this increase. Adding STAT3 phosphorylation inhibitor significantly enhanced the expression inhibition of PD-L1 and NLRC5 induced by HSP27 silencing. Correlation analysis showed a positive correlation in ovarian cancer between NLRC5 and PD-L1. These findings demonstrate that HSP27 modulates PD-L1 and NLRC5 expression through the activation of a common regulator 'STAT3'. Moreover, the positive correlation between PD-L1 and NLRC5 led us to conclude that the upregulation of PD-L1 and the downregulation of MHC class I are two mutually exclusive mechanisms of immune evasion in ovarian cancer.

Intraoperative Ultrasound in the Management of Placenta Accreta Spectrum: Waste of Time or Valuable Step.

Placenta accreta spectrum (PAS) is increasing worldwide paralleling the rising surge of the cesarean section rate. It is well known that sonographic screening for PAS in the second trimester in high-risk patients can predict and reduce major intraoperative hemorrhage during a cesarean hysterectomy. We report the importance of intraoperative ultrasound in the management PAS disorders. It has a crucial role in the reassessment of the placenta location and invasion, reconsidering the cesarean hysterectomy, localization of the hysterotomy, the bladder dissection, and in the conservative treatment. Workshops and hands-on training in intraoperative ultrasound among surgeons must be supported.

Prenatal care in the era of economic collapse.

OBJECTIVES: To describe the effect of economic collapse on prenatal care. METHODS: This is an observational study aiming to depict the changes that occur in prenatal care in the case of an economic collapse. Biochemical screening and ultrasound examinations, as well as medical emigration and private-public sector activity, are discussed. RESULTS: Starting October 2019, Lebanon experienced significant and unprecedented economic degradation leading to 81% degradation of the local currency, 85% inflation, and socio-economic suffering, and the situation is currently still deteriorating. The impact on the medical infrastructure has been global and hit all areas. The crisis is multifaceted, varied in the way it played out across public and private sectors, and did not affect them equally. Some were better prepared than others to cope with severe fiscal pressure mainly through the support of non-governmental organizations. All aspects of prenatal care are affected by the crisis. CONCLUSIONS: Given the multiple strains on the Lebanese health care system today, the plight of antenatal care providers needs assistance to ensure adequate follow-up of pregnancies.

Feasibility of implementing cytology-based cervical cancer screening national program in Lebanon: A pilot study.

OBJECTIVE: To review our national cervical cancer screening program using existing Ministry of Public Health primary healthcare centers (PHCs) and report the impact of women's knowledge, attitude, behavior, and practices on screening uptake and outcome. METHODS: A cross-sectional study on cervical cancer screening offered to sexually active Lebanese women aged 21 years and above visiting PHCs. Exclusions were history of complete hysterectomy, gynecologic cancers, and current pregnancy. Data were collected through a questionnaire and conventional cervical smear performed by trained healthcare providers and sent to one centralized cytopathology laboratory. RESULTS: Of 12 273 eligible women, 1.7% had an abnormal cervical smear test including 161 atypical squamous cells (ASC) of undetermined significance, 6 atypical glandular cells of undetermined significance, 16 low-grade squamous intraepithelial lesion (SIL), 17 ASC-cannot rule out high-grade SIL, 11 high-grade SIL, and one invasive carcinoma. Knowledge and attitudes significantly affected participation in screening; women lacking awareness had rarely undergone a cervical smear. CONCLUSION: In Lebanon, cytology-based cervical cancer screening is feasible within the PHCs. Positive screen incidence was low. Despite previous campaigns, a low level of knowledge persists, and affects women's com with the screening guidelines. Advocacy and awareness activities by key healthcare providers may help to improve participation.

The rate of cesarean delivery changes after internal audit based on the Robson Ten Group Classification System in Lebanon.

OBJECTIVE: To evaluate the efficiency of the Robson classification as an internal clinical audit and feedback of the high rate of cesarean delivery at Hotel Dieu de France, a tertiary referral hospital. METHODS: A pre-post study was conducted, with a retrospective approach in 2018 and 2019, identified as the pre-period (before the implementation of the Robson classification), and with a prospective approach in 2020 and 2021, labeled the post-period. RESULTS: The total number of deliveries during the study period was 2560; 1305 patients were included in the pre-period and 1255 patients delivered in the post-period. No significant differences between the two groups were found. No significant difference was found in the overall rate of cesarean delivery between the first and second periods (57.86% vs 56.72%; P = 0.2). However, a significant decrease in the absolute contribution of groups 3 and 4 (multiparous women without a previous uterine scar with a single cephalic pregnancy, ≥37 weeks of gestation, with spontaneous labor or induced labor) in the overall rate of cesarean delivery was remarked (P = 0.02 and 0.01, respectively). CONCLUSION: The Robson classification seems to be appropriate to monitor and audit the rate of cesarean delivery, but not sufficient to decrease the rate and change the practice.

Long term follow-up after minimally invasive sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a benign condition that can adversely affect women's quality of life. Minimally invasive mesh sacrocolpopexy is an effective surgical treatment for POP. This study aims to assess the perioperative, postoperative, and long term (10 years) outcome of a single institution cohort undergoing minimally invasive sacrocolpopexy. METHODS: This retrospective study included all cases of laparoscopic sacrocolpopexy performed between 2003 and 2016. Patients were contacted by phone in 2022 for long term follow-up. Data on operative time, length of hospital stay, conversion rate, perioperative injuries, early and late postoperative complications and subjective success rates were collected. RESULTS: Ninety-five patients were included aged 60±12 years. Most patients (72%) presented grade 3 POP. Grade of prolapse (3±0.4 vs 3±0.5, p<0.01) and hospital stay (3±1.1 vs 3.1±1.7; p<0.01) were significantly higher in patients who developed early postoperative complications (1st year). At long term follow-up (12±3 years), 48 patients responded. Nine subjects (19%) presented a subjective recurrence with bulge symptoms. Surgery satisfaction was of 79%. The most frequent de novo reported symptom was urge urinary incontinence followed by stress urinary incontinence. Three cases (3%) of mesh erosion were described, all occurred after the 5th postoperative year. CONCLUSIONS: Laparoscopic mesh sacrocolpopexy is a safe surgical technique that shows satisfying and consistent long-term results despite the occasional onset of new urinary symptoms.

Fetal supraventricular tachycardia and maternal COVID-19 vaccination: is there any relationship?

Fetal supraventricular tachycardia accounts for 60-80% of the fetal tachyarrhythmias with prevalence ranging from 1/1000 to 1/25 000 pregnancies. It may be secondary to fetal anomalies or maternal factors. By reviewing the literature, there is no previous article that reports fetal arrhythmia after maternal vaccination. We present herein two cases of fetal supraventricular tachycardia following the administration of the Pfizer-BioNTech COVID-19 vaccine during pregnancy. Continued safety monitoring and more longitudinal follow-up are needed to evaluate the fetal impact after maternal COVID-19 vaccination.

Cesarean section rates in a tertiary referral hospital in Beirut from 2018 to 2020: Our experience using the Robson Classification.

OBJECTIVE: To evaluate the cesarean section rate using the Robson Classification for the first time in Lebanon, at Hôtel-Dieu de France University Hospital, a tertiary referral center in Beirut. METHODS: Routine medical record data that included all live births from January 1, 2018 to September 30, 2020 was investigated. The overall cesarean section rate was recorded, and the size, cesarean section rate, and absolute and relative contributions were calculated within each group. RESULTS: The overall cesarean section rate was 56.8%. The highest relative contribution to this rate came from Robson groups 5, 2 and 10, respectively. A decrease in cesarean section rate was noted in 2020 among women admitted for induction of labor (groups 2 and 4) following the implementation of new department policies and the restrictions caused by the coronavirus disease 2019 pandemic. CONCLUSION: More than 50% of the deliveries in our department were by cesarean sections (CS). Strategies to reduce this rate should include stricter departmental policies for avoidance of unindicated primary CS and raising practitioners' and patients' awareness about trial of labor after cesarean section.

COVID-19 mRNA vaccine in pregnancy and newborn passive immunization: a case report.

AIM: Evaluating the newborn passive immunization after maternal vaccination against SARS-COV-2. CASE PRESENTATION: We present the case of a pregnant woman, with no prior history of COVID-19 infection, who got her second dose of mRNA vaccine against SARS-COV-2, 3 days before the start of her spontaneous labor. She was delivered by cesarean section after dynamical dystocia. Placental cord blood was retrieved immediately and sent to evaluate the titers of COVID-19 antibodies. Vaccine-generated antibodies were present in the umbilical cord with IgG spike >100 AU/ml. CONCLUSION: By reviewing the literature, vaccination seems to give hope about the potential protective effect of the maternal vaccination on her baby. Thus, pregnant women deserve a priority in the COVID-19 vaccination program.