Adverse events and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids - a systematic review and future perspectives.

OBJECTIVES: The aim of this review was to analyze and summarize the most common adverse events (AEs) and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids (UFs) and to establish the risk factors of their occurrence. METHODS: We searched for original research studies evaluating MRgFUS therapy in UFs with outcomes containing AEs and/or complications in different databases (PubMed/MEDLINE, SCOPUS, COCHRANE) until March 2022. Reviews, editorials, opinions or letters, case studies, conference papers and abstracts were excluded from the analysis. The systematic literature search identified 446 articles, 43 of which were analyzed. RESULTS: According to available evidence, the overall incidence of serious complications in MRgFUS therapy is relatively low. No AEs/complications were reported in 11 out of 43 analyzed studies. The mean occurrence of all AEs in the analyzed material was 24.67%. The most commonly described AEs included pain, skin burns, urinary tract infections and sciatic neuropraxia. Major AEs, such as skin ulcerations or deep vein thrombosis, occurred in 0.41% of cases in the analyzed material. CONCLUSION: MRgFUS seems to be safe in UF therapy. The occurrence of AEs, especially major ones, is relatively low in comparison with other methods. The new devices and more experience of their users seem to reduce AE rate. The lack of unification in AE reporting and missing data are the main issues in this area. More prospective, randomized studies with unified reporting and long follow-up are needed to determine the safety in a long-term perspective.

Estimating Excess Mortality Due to Prostate, Breast, and Uterus Cancer during the COVID-19 Pandemic in Peru: A Time Series Analysis.

During the COVID-19 pandemic, most of the deaths in Peru were related to COVID-19; however, cancer deaths have also been exacerbated in the first months of the pandemic. Despite this, excess mortalities of prostate, breast, and uterus cancer are not available by age group and region from January to December 2020. Therefore, we estimated the excess deaths and excess death rates (per 100,000 habitants) due to prostate, breast, and uterus cancer in 25 Peruvian regions. We did a time series analysis. Prostate, breast, and uterus cancer death data for 25 Peruvian regions were retrieved during the COVID-19 pandemic in 2020, as well as data for up to 3 years prior (2017-2019) from the Sistema Informatico Nacional de Defunciones at the Ministry of Health of Peru. Deaths in 2020 were defined as observed deaths. The expected deaths (in 2020) were estimated using the average deaths over 3 preceding years (2017, 2018 and 2019). Excess mortality was calculated as the difference between observed mortality and expected mortality in 2020. We estimated that the number of excess deaths and the excess death rates due to prostate, breast, and uterus cancer were 610 deaths (55%; 12.8 deaths per 100,000 men), 443 deaths (43%; 6 deaths per 100,000 women), and 154 deaths (25%; 2 deaths per 100,000 women), respectively. Excess numbers of deaths and excess death rates due to prostate and breast cancer increased with age. These excess deaths were higher in men aged ≥ 80 years (596 deaths (64%) and 150 deaths per 100,000 men) and women aged 70-79 years (229 deaths (58%) and 15 deaths per 100,000 women), respectively. In summary, during the COVID-19 pandemic, there were excess prostate and breast cancer mortalities in 2020 in Peru, while excess uterus cancer mortalities were low. Age-stratified excess death rates for prostate cancer and breast cancer were higher in men ≥ 80 years and in women ≥ 70 years, respectively.

Development of placental lesions after recovery from COVID-19 during pregnancy: case-control study.

OBJECTIVE: To study whether the occurrence and type of placental lesions vary according to the time of onset of COVID-19 in pregnant women. DESIGN: Case-control study. SETTING: Departments of Gynaecology-Obstetrics and Pathology, Strasbourg University Hospital, France. POPULATION: Cases were 49 placentas of women with COVID-19. Controls were 50 placentas from women who had a past history of molar pregnancy. COVID-19 placentas were categorised based on whether birth occurred at more or less than 14 days post-infection. METHODS: Comparison between case and controls. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes were recorded. Macroscopic and microscopic examination of the placentas was performed. RESULTS: The rate of vascular complications was higher in the COVID groups than in the controls (8 [16.3%] versus 1 [2%], p = 0.02). Signs of fetal (22[44.9%] versus 13 [26%], p = 0.05) and maternal (44 [89.8%] versus 36 [72.0%], p = 0.02) vascular malperfusion and signs of inflammation (11 [22.4%] versus 3 [6.0%], p = 0.019) were significantly more common in the COVID-19 groups than in the control group. Fetal malperfusion lesions (9 [39.1%] versus 13 [50.0%], p = 0.45) and placental inflammation (4 [17.4%] versus 7 [26.9%], p = 0.42) rates were not significantly different between the two COVID-19 groups. Chronic villitis was significantly more common when the delivery occurred >14 days after infection than in the group that delivered <14 days after infection (7 [26.9%] versus 1 [4.4%], p = 0.05). CONCLUSIONS: Our study suggests that SARS-COV-2 induces placental lesions that evolve after disease recovery, especially with the development of inflammatory lesions, such as chronic villitis.

A rare case of pulmonary benign metastasising leiomyomatosis in a woman with a previous history of hysterectomy for uterine fibroids.

Benign metastasising leiomyomatosis (BML) is a rare disease, predominantly seen in premenopausal women. It poses a diagnostic dilemma and can be misdiagnosed as malignancy. Here we present a case of 41-year-old woman with a previous history of hysterectomy 10 years ago for multiple fibroids. She presented with shortness of breath and chest discomfort. Chest X-ray showed pulmonary infiltrates. She was diagnosed with sarcoidosis and treated with steroids without any improvement. Further investigations including CT scan and bronchoscopy and lavage failed to confirm a diagnosis. Subsequently she underwent video-assisted thoracoscopic surgery and histopathology revealed leiomyomatosis (so-called leiomyomatous hamartomas/benign metastasising leiomyomatosis). Oestrogen and progesterone receptors showed diffuse and strong nuclear staining. The patient was commenced on tamoxifen and a repeat chest X-ray in 8 weeks showed significant improvement. In women of reproductive age with previous hysterectomy and multiple lung nodules on imaging, the diagnosis of BML should be taken into consideration.

Life-threatening rupture of interstitial ectopic pregnancy: a rare presentation of metastatic invasive mole.

An invasive mole is an uncommon type of gestational trophoblastic disease, and if considering its implantation in an interstitial extrauterine location, we are facing a rarer condition.There are 14 cases described of interstitial ectopic gestational trophoblastic disease. As far as we know, we present the third case of invasive mole within interstitial location, in this case with pulmonary metastases.The diagnosis of an interstitial implantation is challenging. Our patient was initially diagnosed with an intrauterine hydatidiform molar pregnancy, and a uterine aspiration was performed. Two weeks later, she presented with haemodynamical instability due to a severe haemoperitoneum. A laparotomy was immediately performed and revealed a ruptured interstitial pregnancy with molar vesicle extrusion. Besides its rarity, we highlight the clinical presentation with hypovolaemic shock due to rupture of ectopic pregnancy in a young nulliparous woman, which required an emergent surgical approach with lifesaving purpose while preserving future fertility.

Bizarre Chorionic-type Trophoblast in Second-trimester and Third-trimester Placentas: Clinicopathologic Characterization of a Placental Pseudoneoplastic Lesion.

Bizarre (atypical/symplastic) cells have been described in various gynecologic normal tissues and benign neoplasms. This type of bizarre cytologic change is usually an incidental finding and is regarded as a benign process. We describe 17 cases of bizarre chorionic-type trophoblast in second-trimester and third-trimester placentas that created concern for an underlying/undersampled or incipient intraplacental trophoblastic neoplasm, predominantly found in intervillous trophoblastic islands (11/17), placental septae (6/17), chorionic plate (1/17), and/or the chorion layer of fetal membranes (2/17). The bizarre trophoblastic cells exhibited sheet-like or nested architecture, had a multifocal/patchy distribution, and/or were present as individual cells within hyaline stroma; they were characterized by large nuclei with smudgy chromatin and occasional intranuclear pseudoinclusions. The degree of atypia was classified as mild (0/17), moderate (3/17), or severe (14/17). Mitotic figures and necrosis were not identified. A dual immunohistochemical stain for trophoblast (hydroxyl-delta-5-steroid dehydrogenase) and a proliferation marker (Ki-67), performed in 15 cases, demonstrated 0% to very low proliferative activity within the bizarre trophoblast (0% to 2% [10/15], 3% to 8% [5/15]). Immunohistochemical stains for fumarate hydratase showed intact/retained expression in the bizarre cells in 7 of 7 cases. Clinical follow-up ranged from 1 to 45 months, and all patients were alive and well without subsequent evidence of a gestational trophoblastic or other neoplasms. We conclude that bizarre chorionic-type trophoblast in second-trimester or third-trimester placentas have the potential to mimic an intraplacental trophoblastic neoplasm but are likely a benign degenerative change. This study expands the spectrum of bizarre cells that occur in the gynecologic tract.

A Call-to-Action for Clinicians to Implement Evidence-Based Best Practices When Caring for Women with Uterine Fibroids.

Uterine fibroids are common benign tumors that occur in up to 80% of women. Approximately half of the women affected experience considerable physical, psychological, and economic burdens and impact on quality of life due to symptoms such as heavy menstrual bleeding, pelvic pain, and infertility. Several medical and surgical options are available to treat uterine fibroids; however, healthcare providers may benefit from practical guidance in the development of individualized treatment plans based on a personalized approach. Medical treatments and minimally invasive procedures are generally preferred by most patients before considering more invasive, higher risk surgical interventions. In general, patient-centered, uterine-preserving procedures may be prioritized based on the patient's goals and the clinical scenario. Occasionally, hysterectomy may be the preferred treatment option for some patients who require definitive treatment. This call-to-action highlights recent challenges to patient care, including radical shifts in physician-patient interactions due to the COVID-19 pandemic and recent changes to evidence-based, clinically approved therapies. This report also reviews contemporary recommendations for women's health providers in the diagnosis and medical and surgical management of uterine fibroids. This call-to-action aims to empower healthcare providers to optimize the quality of care for women with uterine fibroids utilizing the best available evidence and best practices.

Evaluation of Serologic Changes of IgG and IgM Antibodies Associated with SARS-COV-2 in Cancer Patients: A Cohort Seroprevalence Study.

BACKGROUND: While the coronavirus disease 2019 (COVID-19) pandemic spreads, there is increasing evidence to suggest the elevated risk of SARS-CoV-2 infection and following morbidity and mortality in cancer patients. Serology testing using ELISA proposes major advantages as a diagnostic and preventive tool to control the present SARS-CoV-2 outbreak. This cohort study was to determine the SARS-CoV-2 seroconversion in asymptomatic cancer patients. METHODS: Patients in all age groups and with any type of cancer who have been in remission or have stable disease and received their latest anticancer therapy over 2 months ago included in the study. All patients were evaluated for COVID-19 symptoms and only asymptomatic patients were enrolled for serologic screening for SARS-CoV-2. Serum samples evaluated serologically for SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay. RESULTS: A total of 168 asymptomatic cancer patients were included in the study. Of the 168 cases with a history of cancer who were asymptomatic for Covid-19, 29 cases (17.26%) had a positive serological test. CONCLUSION: In conclusion, in the present study asymptomatic cancer patients revealed 17% seropositivity, approximately equal to the general population of the same age, sex, geographic region, and epidemic status. Asymptomatic infections should further be investigated and considered as playing an important role in the COVID-19 transmission chain.

Loss of Reproductive Ability due to Late Application of Young Refugee with Choriocarcinoma During the COVID-19 Pandemic.

Choriocarcinoma is an aggressive malignant trophoblastic neoplasm. The rapid growth of neoplastic tissue and myometrial invasion can cause uterine perforation. It is important to quickly diagnose the disease and plan treatment because these tumors are nearly always curable, and fertility can be preserved in most cases with proper management. The outbreak of novel coronavirus disease has affected the whole world since January 2019 and caused delays in treatment and follow-up of patients all over the world. In this study, we report a case of choriocarcinoma who postponed her admission to the hospital after diagnosis because she was afraid of the pandemic and lost her fertility due to uterine rupture and massive intra-abdominal hemorrhage.

A possible association between hydatidiform mole and the COVID-19 pandemic: A retrospective cohort study.

OBJECTIVE: To confirm an increase in the number of women with molar pregnancy during the COVID-19 pandemic. METHODS: In this retrospective cohort study, all patients with complete or partial mole diagnosed at our institution between January 1, 2010 and October 31, 2020, were included. To verify whether there was an increase in the incidence of hydatidiform mole (HM) and deliveries in 2020, the incidences for each year from January 2010 to October 2020 were recorded. In addition, we identified all women who were diagnosed with HM from January to October 2020, and compared them with a control group who underwent uterine evacuation for missed abortion of a singleton pregnancy during the same period. We also documented the time taken to diagnose missed abortion or molar pregnancy to check if a delay in diagnosis can explain the increase in HM incidence. RESULTS: Between 2016 and 2019, there was a statistically significant increase in the incidence of molar pregnancy. A further increase occurred in 2020 (odds ratio = 2.071). The mean gestational age of the embryo at the time of diagnosis was smaller in the HM group than in the missed abortion group (6.3 ± 1.67-7.4 ± 2.4, one-sided P = 0.034), meaning that it took more time (days) to diagnose molar pregnancy than missed abortion (22.38 ± 10.32 vs. 15.83 ± 7.83 days, P = 0.012). CONCLUSION: There was a significant increase in the incidence of molar pregnancy during the COVID-19 pandemic, possibly because of the delay in receiving medical care. We recommend providing gynecological primary care services during a crisis, such as a pandemic.

Associations Between DPP9 Expression, Survival and Gene Expression Signature in Human Hepatocellular Carcinoma: Comprehensive In Silico Analyses (preprint)

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is essential for human survival and the DPP4 protease family is important in cancer pathogenesis.

Suspension of ulipristal acetate for uterine fibroids during ongoing EMA's review of liver injury risk: Unfortunate timing during the Covid-19 pandemic!

OBJECTIVE: EMA decided that with ulipristal acetate (UPA) treatment for uterine fibroids, should be discontinued due to the associated risk of hepatic failure, We analyzed whether the risk of recurrent symptoms due to fibroids may lead to an increased risk of Covid -19 infection and death, that would exceed the former risk of hepatic failure and transplantation. STUDY DESIGN, SIZE, DURATION: We used a Markov model to generate probabilities. PARTICIPANTS/MATERIALS, SETTING, METHODS: There are currently about 36,250 treated patients in Europe. We estimated bleeding probabilities, while using or discontinuing UPA, which may induce a need of medical or surgical management in symptomatic patients, and increase the risk of acquiring a Covid-19 infection, and die from it. We also estimated the risk of suffering a hepatic failure and hepatic transplantation. MAIN RESULTS AND THE ROLE OF CHANCE: Based on our assumptions, ceasing UPA during a Covid 19 pandemic may be associated with a fatality ratio between 4 and 18, due to the Pandemic, whereas pursuing UPA would be associated with a fatality rate due to the pandemic between 1-2, and an added fatality rate due to hepatic impairment of 1. The added risk of stopping UPA may range between 2 and 15 additional deaths. Our calculations suggest that the decision to stop UPA in the middle of the Covid- 19 pandemic may be untimely, since it may result in an increased risk of Covid-19 infection, due to the recurrence of symptoms and the need for medical and surgical treatment. WIDER IMPLICATIONS OF THE FINDINGS: A decision, like the one EMA took need to be taken in a wider health context of a population, than simply analyzing its role as regulating agent for medications.