Recurrent Cesarean scar pregnancy: case series and literature review.

OBJECTIVES: To determine the rate of recurrent Cesarean scar pregnancy (CSP) in our clinical practices and to evaluate whether the mode of treatment of a CSP is associated with the risk of recurrent CSP, as well as to review the published literature on recurrent CSP. METHODS: We performed a retrospective search of our six obstetric and gynecological departmental ultrasound databases for all CSPs and recurrent CSPs between 2010 and 2019. We extracted various data, including number of CSPs with follow-up, number of cases attempting and number achieving pregnancy following treatment of CSP and number of recurrent CSPs, as well as details of the treatment of the original CSP. After analyzing the clinical data, we evaluated whether the mode of treatment terminating the previous CSP was associated with the risk of recurrent CSP. We also performed a PubMed search for: 'recurrent Cesarean scar pregnancy' and 'recurrent Cesarean scar ectopic pregnancy'. Articles were reviewed for year of publication, and extraction and analysis of the same data as those obtained from our departmental databases were performed. RESULTS: Our database search identified 252 cases of CSP. The overall rate of clinical follow-up ranged between 71.4% and 100%, according to treatment site (mean, 90.9%). Among these, 105 women had another pregnancy after treatment of the previous CSP. Of these, 36 (34.3%) pregnancies were recurrent CSP, with 27 women having a single recurrence and three women having multiple recurrences, one with two, one with three and one with four. We did not find any particular single or combination treatment mode terminating the previous CSP to be associated with recurrent CSP. The literature search identified 17 articles that yielded sufficient information for us to evaluate their reported prevalence of recurrent CSP. These reported 1743 primary diagnoses of CSP, of which 944 had reliable follow-up. Data were available for 489 cases that attempted to conceive again after treatment of a previous CSP, and on the 327 pregnancies achieved. Of these, 67 (20.5%) were recurrent CSP. CONCLUSIONS: On the basis of our pooled clinical data and review of the literature, recurrent CSP is apparently more common than was previously assumed based upon mostly single-case reports or series with few cases. This should be borne in mind when counseling patients undergoing treatment for CSP regarding their risk of recurrence. We found no obvious causal relationship or association between the type of treatment of the previous CSP and recurrence of CSP. Patients who become pregnant after treatment of a CSP should be encouraged to have an early (5-7-week) first-trimester transvaginal scan to determine the location of the gestation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical spectrum of BICD2 mutations.

BACKGROUND AND PURPOSE: Mutations in the BICD2 gene cause autosomal dominant lower extremity-predominant spinal muscular atrophy 2A (SMALED2A), a condition that is associated with a specific pattern of thigh and calf muscle involvement when studied by magnetic resonance imaging (MRI). Patients may present minor clinical sensory impairment, but objective sensory involvement has yet to be demonstrated. METHODS: We collected clinical data from 11 patients from five different families carrying mutations in BICD2. Genetic diagnosis was achieved using gene panel testing and skin biopsies were taken from two patients to study the epidermal nerve fiber density. RESULTS: In the studied patients, three new pathogenic mutations were detected as well as the already defined pathogenic p.Ser107Leu mutation. The most frequent clinical picture was characterized by lower-limb weakness in combination with foot deformities. One patient manifested clinical and electrophysiological sensory impairment, and the epidermal nerve fiber density study of another patient revealed the existence of a small-fiber neuropathy. Muscle MRI showed a common pattern of fat deposition including selective involvement of gluteus medius and minimus at the pelvic level, the anterior compartment of the thigh and the posterior compartment of the calf, with only mild or no involvement of the intrinsic foot muscles. CONCLUSIONS: We report three new pathogenic mutations in the BICD2 gene. Muscle MRI confirms the existence of a selective pattern of thigh and leg muscle involvement in SMALED2A, providing additional information regarding pelvic and foot muscles. Moreover, our results raise the possibility of sensory involvement in the disease.

Value of first-trimester ultrasound in prediction of third-trimester sonographic stage of placenta accreta spectrum disorder and surgical outcome.

OBJECTIVES: To explore whether early first-trimester ultrasound can predict the third-trimester sonographic stage of placenta accreta spectrum (PAS) disorder and to elucidate whether combining first-trimester ultrasound findings with the sonographic stage of PAS disorder can stratify the risk of adverse surgical outcome in women at risk for PAS disorder. METHODS: This was a retrospective analysis of prospectively collected data from women with placenta previa, and at least one previous Cesarean delivery (CD) or uterine surgery, for whom early first-trimester (5-7 weeks' gestation) ultrasound images could be retrieved. The relationship between the position of the gestational sac and the prior CD scar was assessed using three sonographic markers for first-trimester assessment of Cesarean scar (CS) pregnancy, reported by Calí et al. (crossover sign (COS)), Kaelin Agten et al. (implantation of the gestational sac on the scar vs in the niche of the CS) and Timor-Tritsch et al. (position of the center of the gestational sac below vs above the midline of the uterus), by two different examiners blinded to the final diagnosis and clinical outcome. The primary aim of the study was to explore the association between first-trimester ultrasound findings and the stage of PAS disorder on third-trimester ultrasound. Our secondary aim was to elucidate whether the combination of first-trimester ultrasound findings and sonographic stage of PAS disorder can predict surgical outcome. Logistic regression analysis and area under the receiver-operating-characteristics curve (AUC) were used to analyze the data. RESULTS: One hundred and eighty-seven women with vasa previa were included. In this cohort, 79.6% (95% CI, 67.1-88.2%) of women classified as COS-1, 94.4% (95% CI, 84.9-98.1%) of those with gestational-sac implantation in the niche of the prior CS and 100% (95% CI, 93.4-100%) of those with gestational sac located below the uterine midline, on first-trimester ultrasound, were affected by the severest form of PAS disorder (PAS3) on third-trimester ultrasound. On multivariate logistic regression analysis, COS-1 (odds ratio (OR), 7.9 (95% CI, 4.0-15.5); P < 0.001), implantation of the gestational sac in the niche (OR, 29.1 (95% CI, 8.1-104); P < 0.001) and location of the gestational sac below the midline of the uterus (OR, 38.1 (95% CI, 12.0-121); P < 0.001) were associated independently with PAS3, whereas parity (P = 0.4) and the number of prior CDs (P = 0.5) were not. When translating these figures into diagnostic models, first-trimester diagnosis of COS-1 (AUC, 0.94 (95% CI, 0.91-0.97)), pregnancy implantation in the niche (AUC, 0.92 (95% CI, 0.89-0.96)) and gestational sac below the uterine midline (AUC, 0.92 (95% CI, 0.88-0.96)) had a high predictive accuracy for PAS3. There was an adverse surgical outcome in 22/187 pregnancies and it was more common in women with, compared to those without, COS-1 (P < 0.001), gestational-sac implantation in the niche (P < 0.001) and gestational-sac position below the uterine midline (P < 0.001). On multivariate logistic regression analysis, third-trimester ultrasound diagnosis of PAS3 (OR, 4.3 (95% CI, 2.1-17.3)) and first-trimester diagnosis of COS-1 (OR, 7.9 (95% CI, 4.0-15.5); P < 0.001), pregnancy implantation in the niche (OR, 29.1 (95% CI, 8.1-79.0); P < 0.001) and position of the sac below the uterine midline (OR, 6.6 (95% CI, 3.9-16.2); P < 0.001) were associated independently with adverse surgical outcome. When combining the sonographic coordinates of the three first-trimester imaging markers, we identified an area we call high-risk-for-PAS triangle, which may enable an easy visual perception and application of the three methods to prognosticate the risk for CS pregnancy and PAS disorder, although it requires validation in large prospective studies. CONCLUSIONS: Early first-trimester sonographic assessment of pregnancies with previous CD can predict reliably ultrasound stage of PAS disorder. Combination of findings on first-trimester ultrasound with second- and third-trimester ultrasound examination can stratify the surgical risk in women affected by a PAS disorder. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

New sonographic marker of borderline ovarian tumor: microcystic pattern of papillae and solid components.

OBJECTIVE: To describe and evaluate the utility of a new sonographic microcystic pattern, which is typical of borderline ovarian tumor (BOT) papillary projections, solid component(s) and/or septa, as a new ultrasound marker that is capable of distinguishing BOT from other adnexal masses, and to present/obtain histologic confirmation. METHODS: In this retrospective study, we identified women with a histologic diagnosis of BOT following surgical resection who had undergone preoperative transvaginal ultrasound (TVS) examination. All images were reviewed for presence or absence of thin-walled, fluid-filled cluster(s) of 1-3-mm cystic formations, associated with solid component(s), papillary projections and/or septa. From the same cases, histopathologic slides of each BOT were examined for presence of any of these microcystic features which had been identified on TVS. To confirm that the microcystic TVS pattern is unique to BOTs, we also selected randomly from our ultrasound and surgical database 20 cases of epithelial ovarian cancer and 20 cases of benign cystadenoma, for review by the same pathologists. To confirm the novelty of our findings, we searched PubMed for literature published in the English language between 2010 and 2018 to determine whether the association between microcystic tissue pattern and BOT has been described previously. RESULTS: Included in the final analysis were 62 patients (67 ovaries) with preoperative TVS and surgically confirmed BOT on pathologic examination. The mean patient age at surgery was 39.8 years. The mean BOT size at TVS was 60.7 mm. Of the 67 BOTs, 47 (70.1%) were serous, 15 (22.4%) were mucinous and five (7.5%) were seromucinous. We observed on TVS a microcystic pattern in the papillary projections, solid component(s) and/or septa in 60 (89.6%) of the 67 BOTs, including 46 (97.9%) of the 47 serous BOTs, 11 (73.3%) of the 15 mucinous BOTs and three (60.0%) of the five seromucinous BOTs. On microscopic evaluation, 60 (89.6%) of the 67 samples had characteristic 1-3-mm fluid-filled cysts similar to those seen on TVS. In seven cases there was a discrepancy between sonographic and histologic observation of a microcystic pattern. The 20 cystadenomas were mostly unilocular and/or multilocular and largely avascular. None of them or the 20 epithelial ovarian malignancies displayed microcystic characteristics, either on TVS or at histology. On review of 23 published articles in the English medical literature, containing 163 sonographic images of BOT, we found that, while all images contained it, there was no description of the microcystic tissue pattern. CONCLUSION: We report herein a novel sonographic marker of BOT, a 'microcystic pattern' of BOT papillary projections, solid component(s) and/or septa. This was seen in the majority of both serous and mucinous BOT cases. Importantly, based on comparison of sonographic images and histopathology of benign entities and malignancies, the microcystic appearance seems to be unique to BOTs. No similar description has been published previously. Utilization of this new marker should help to identify BOT correctly, discriminating it from ovarian cancer and benign ovarian pathology, and should ensure appropriate clinical and surgical management. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester detection of abnormally invasive placenta in high-risk women: systematic review and meta-analysis.

OBJECTIVES: The primary aim of this systematic review was to ascertain whether ultrasound signs suggestive of abnormally invasive placenta (AIP) are present in the first trimester of pregnancy. Secondary aims were to ascertain the strength of association and the predictive accuracy of such signs in detecting AIP in the first trimester. METHODS: An electronic search of MEDLINE, EMBASE, CINAHL and Cochrane databases (2000-2016) was performed. Only studies reporting on first-trimester diagnosis of AIP that was subsequently confirmed in the third trimester either during operative delivery or by pathological examination were included. Meta-analysis of proportions, random-effects meta-analysis and hierarchical summary receiver-operating characteristics curve analysis were used to analyze the data. RESULTS: Seven studies, involving 551 pregnancies at high risk of AIP, were included. At least one ultrasound sign suggestive of AIP was detected in 91.4% (95% CI, 85.8-95.7%) of cases with confirmed AIP. The most common ultrasound feature in the first trimester of pregnancy was low implantation of the gestational sac close to a previous uterine scar, which was observed in 82.4% (95% CI, 46.6-99.8%) of cases. Anechoic spaces within the placental mass (lacunae) were observed in 46.0% (95% CI, 10.9-83.7%) and a reduced myometrial thickness in 66.8% (95% CI, 45.2-85.2%) of cases affected by AIP. Pregnancies with a low implantation of the gestational sac had a significantly higher risk of AIP (odds ratio, 19.6 (95% CI, 6.7-57.3)), with a sensitivity and specificity of 44.4% (95% CI, 21.5-69.2%) and 93.4% (95% CI, 90.5-95.7%), respectively. CONCLUSIONS: Ultrasound signs of AIP can be present during the first trimester of pregnancy, even before 11 weeks' gestation. Low anterior implantation of the placenta/gestational sac close to or within the scar was the most commonly seen early ultrasound sign suggestive of AIP, although its individual predictive accuracy was not high. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Ecotoxicidad aguda en Physa cubensis P. y Artemia salina L. de 8 antibacterianos con riesgo ambiental / Acute toxicity in Physa cubensis P. and Artemia salina L. of 8 antibiotics with environmental risk

Los productos farmacéuticos son ampliamente utilizados en todo el planeta. Existe una creciente preocupación por los efectos que los medicamentos consumidos y los desechos de estos producen en el ambiente. A pesar del gran uso de los antibacterianos no son muy investigados como contaminantes, prestándose mayor atención a la antibioresistencia por lo que el objetivo de la investigación fue evaluar la ecotoxicidad aguda de antibacterianos. Teniendo en cuenta el consumo de los antibacterianos y la predicción de sus concentraciones ambientales así como su ecoxicidad en Lactuca sativa L ya previamente determinados en anteriores investigaciones se determinó el riesgo ecotoxicológico en Artemia salina L. y Physa cubensis P. En el ensayo de Artemia salina la Ceftazidima se clasifica como muy tóxico con valor de CL50 de 0,060773 g/L, la Cefepima con valor de 0,993731 g/L como moderadamente tóxica y el resto de los antibacterianos evaluados se clasifican como no tóxicos. En los bioensayos en Physa cubensis Cefepima y Cefazolina ocasionaron la mayor mortalidad con CL50 de 0,000270 y 0,025684 g/L respectivamente y los que indujeron menor mortalidad fueron Vancomicina y Amoxicilina/Sulbactam con CL50 de 1,528440 y 1,055492 g/L. El vertimiento de residuos de antibacterianos puede ser causa de contaminación ambiental perjudicial para algunas especies (AU)

Pharmaceuticals are widely used all over the planet. There is growing concern about the effects that drugs and its residues produce in the environment. Despite the wide use of antibacterial, they are not very investigated as pollutants, paying greater attention to the antibiotic resistance, so the objective of this research was to evaluate the antibacterial acute ecotoxicity. Taking into account the antibacterial consumption and the prediction of their environmental concentrations as well as their ecotoxicity in Lactuca sativa L already determined in previous research, the ecotoxicological risk was determined in Artemia salina L. and Physa cubensis P. In the Artemia salina trial Ceftazidime is classified as very toxic with LC50 value of 0.060773g/L, Cefepime with value of 0.993731g/L is classified as moderately toxic and the rest of antibacterial evaluated are classified as non-toxic. In bio trials of Physa cubensis, Cefepime and Cefazolin caused the greatest mortality with LC50 0.000270 and 0.025684g/L respectively, and the ones that led lower mortality were Vancomycin and Amoxicillin/Sulbactam with LC50 of 1.528440 and 1.055492 g/L. The dumping of antibiotics residues can be the cause of environmental pollution, detrimental to some species (AU)

Foley balloon catheter to prevent or manage bleeding during treatment for cervical and Cesarean scar pregnancy.

OBJECTIVE: To demonstrate the efficacy of placement and inflation of Foley balloon catheters prophylactically to prevent, or as an adjuvant therapy to control, bleeding in women undergoing treatment for Cesarean scar pregnancy (CSP) or cervical pregnancy (CxP). METHODS: This was a retrospective study of 18 women with either CSP (n = 16) or CxP (n = 2), who underwent Foley balloon catheter placement under continuous transvaginal or transabdominal ultrasound guidance to prevent or manage bleeding following treatment, which in most cases comprised local (intragestational sac) and intramuscular (IM) methotrexate (MTX) injections. In eight cases, the balloon catheter was placed immediately following local and/or IM MTX treatment, either because of bleeding or prophylactically; in eight cases, the catheter was placed as part of a two-step protocol, with patients first treated with local and IM MTX injection, then suction aspiration on Day 4 or 5, followed by planned insertion of a balloon catheter; in one patient the balloon was placed on Day 21 after local and IM MTX treatment, due to sudden bleeding; and in one case of a heterotopic pregnancy, one intrauterine and one cervical, the balloon was placed due to severe bleeding. Human chorionic gonadotropin (hCG) levels were evaluated weekly following MTX injection. RESULTS: Gestational ages at balloon placement ranged between 5 and 12 + 2 weeks. All embryos/fetuses, with the exception of the cervical heterotopic one, had heart activity and catheter placement was well-tolerated by all women. The balloon tamponade effectively reduced or prevented maternal vaginal bleeding in all except one patient; this woman had a heterotopic CxP and required abdominal robotic cerclage to control the bleeding. Catheters were kept in place for a mean of 3.6 (range, 1-6) days. hCG levels returned to low or zero levels within 19-82 days following MTX injection. Fifteen women required antibiotic treatment following the procedure. One woman with CSP developed an arteriovenous malformation requiring uterine artery embolization. CONCLUSION: Ultrasound-guided placement and inflation of Foley balloon catheters was easy to perform and well-tolerated by patients undergoing treatment for CSP or CxP, and successfully prevented or helped in the management of bleeding complications. Based on our experience and previous publications we suggest having the option of balloon catheter insertion available when local treatment of CSP or CxP is undertaken.

Cesarean scar pregnancy is a precursor of morbidly adherent placenta.

OBJECTIVE: To provide further sonographic, clinical and histological evidence that Cesarean scar pregnancy (CSP) is a precursor to and an early form of second- and third-trimester morbidly adherent placenta (MAP). METHODS: This is a report of 10 cases of CSP identified early, in which the patients decided to continue the pregnancy, following counseling that emphasized the possibility of both significant pregnancy complications and a need for hysterectomy. Pregnancies were followed at 2-4-week intervals with ultrasound scans and customary monitoring. The aim was for patients to reach near term or term and then undergo elective Cesarean delivery and, if necessary, hysterectomy. Charts, ultrasound images, operative reports and histopathological examinations of the placentae were reviewed. RESULTS: The ultrasound diagnosis of CSP was made before 10 weeks. By the second trimester, all patients exhibited sonographic signs of MAP. Nine of the 10 patients delivered liveborn neonates between 32 and 37 weeks. In the tenth pregnancy, progressive shortening of the cervix and intractable vaginal bleeding prompted termination, with hysterectomy, at 20 weeks. Two other patients in the cohort had antepartum complications (bleeding at 33 weeks in one case and contractions at 32 weeks in the other). All patients underwent hysterectomy at the time of Cesarean delivery, with total blood loss ranging from 300 to 6000 mL. Placenta percreta was the histopathological diagnosis in all 10 cases. CONCLUSION: The cases in this series validate the hypothesis that CSP is a precursor of MAP, both sharing the same histopathology. Our findings provide evidence that can be used to counsel patients with CSP, to enable them to make an informed choice between first-trimester termination and continuation of the pregnancy, with its risk of premature delivery and loss of uterus and fertility.

Cesarean scar pregnancy and early placenta accreta share common histology.

OBJECTIVE: To determine, by evaluation of histological slides, images and descriptions of early (second-trimester) placenta accreta (EPA) and placental implantation in cases of Cesarean scar pregnancy (CSP), whether these are pathologically indistinguishable and whether they both represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester. METHODS: The database of a previously published review of CSP and EPA was used to identify articles with histopathological descriptions and electronic images for pathological review. When possible, microscopic slides and/or paraffin blocks were obtained from the original researchers. We also included from our own institutions cases of CSP and EPA for which pathology specimens were available. Two pathologists examined all the material independently and, blinded to each other's findings, provided a pathological diagnosis based on microscopic appearance. Interobserver agreement in diagnosis was determined. RESULTS: Forty articles were identified, which included 31 cases of CSP and 13 cases of EPA containing histopathological descriptions and/or images of the pathology. We additionally included six cases of CSP and eight cases of EPA from our own institutions, giving a total of 58 cases available for histological evaluation (37 CSP and 21 EPA) containing clear definitions of morbidly adherent placenta. In the 29 cases for which images/slides were available for histopathological evaluation, both pathologists attested to the various degrees of myometrial and/or scar tissue invasion by placental villi with scant or no intervening decidua, consistent with the classic definition of morbidly adherent placenta. Based on the reviewed material, cases with a diagnosis of EPA and those with a diagnosis of CSP showed identical histopathological features. Interobserver correlation was high (kappa = 0.93). CONCLUSIONS: EPA and placental implantation in CSP are histopathologically indistinguishable and may represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester.