Accelerated Atherosclerosis and Cardiovascular Toxicity Induced by Radiotherapy in Breast Cancer.

The number of patients diagnosed with breast cancer and cardiovascular disease is continuously rising. Treatment options for breast cancer have greatly evolved, but radiotherapy (RT) still has a key role in it. Despite many advances in RT techniques, cardiotoxicity is one of the most important side effects. The new cardio-oncology guidelines recommend a baseline evaluation, risk stratification and follow-up of these patients. Cardiotoxicity induced by RT can be represented by almost all forms of cardiovascular disease, with atherosclerosis being the most frequent. An interdisciplinary team should manage these patients, in order to have maximum therapeutic effect and minimum cardiovascular toxicity. This review will summarize the current incidence, risk factors, mechanisms and follow-up of RT-induced cardiovascular toxicity.

Hyperglycosylated-hCG: Its Role in Trophoblast Invasion and Intrauterine Growth Restriction.

Human chorionic gonadotropin (hCG) is produced by the placenta and its roles have been studied for over a century, being the first known pregnancy-related protein. Although its main role is to stimulate the production of progesterone by corpus luteal cells, hCG does not represent just one biologically active molecule, but a group of at least five variants, produced by different cells and each with different functions. The hyperglycosylated variant of hCG (H-hCG) plays a key role in trophoblast invasion, placental development and fetal growth. During trophoblast invasion, H-hCG promotes extravillous cytotrophoblast cells to infiltrate the decidua, and also to colonize and remodel the spiral arteries in to low resistance, larger-diameter vessels. As fetal growth is heavily reliant on nutrient availability, impaired trophoblast invasion and remodeling of the uterine arteries, leads to a defective perfusion of the placenta and fetal growth restriction. Understanding the function of H-hCG in the evolution of the placenta might unveil new ways to manage and treat fetal growth restriction.

Operator experience impact on the evaluation of still images of a first trimester cardiac assessment protocol.

OBJECTIVE: Congenital heart disease (CHD) is the most common birth defect and represents the leading cause for mortality and morbidity in infants and young adults. Early fetal echocardiography is usually considered a highly specialized scan. The goal of this study is to evaluate the impact of operator's experience in assessing still images of the 4-chamber view and 3-vessels view and to evaluate the feasibility and the performance of a first trimester screening protocol for CHD. METHODS: An online questionnaire consisting of still images of the 4-camber view and 3-vessel view from 50 normal and abnormal cases was reviewed by an expert group made of seven obstetricians specialized in fetal medicine and a nonexpert group made of 13 obstetricians that are certified in ultrasound. After individually visualizing each image set made of the 4-chamber view and 3-vessel view, they had to conclude if the case was normal or abnormal and what images were abnormal. RESULTS: A total of 50 image sets of both normal and abnormal fetal hearts were examined by the 20 reviewers, resulting in 1000 evaluations. The expert group achieved a detection rate of 97.1% with a false positive rate of 5.7%. The nonexpert group achieved also a good detection rate of 91.3% but with a much higher false positive rate of 33.9%. The most frequently missed CHD involved the great arteries and had a normal 4-chamber view. In the majority of false positive cases the 3-vessel view was incorrectly interpreted as abnormal. CONCLUSIONS: A screening protocol for CHD, based on the 4-chamber view and 3-vessel view alone can offer a good detection rate for CHD with a small false positive rate, but only if it is implemented by highly specialized sonographers.

Ultrasound Patterns in the First Trimester Diagnosis of Congenital Heart Disease.

Congenital heart disease (CHD) is the most common birth defect, with a reported prevalence of 5-12 per 1000 live births. Very recently, the American Institute of Ultrasound in Medicine published a guideline recommending the use of the four-chamber and the three-vessel and trachea views to screen for CHD in the first trimester of pregnancy. Our aim is to present abnormal image patterns that are seen in the four-chamber, three-vessel, and trachea views of the fetal heart in the first trimester and to describe their association with specific CHD types. We used a total of 29 cases of CHD from the archives of Filantropia Hospital and the Maternal and Child Health Institute (INSMC) fetal medicine units. We selected cases with a clear and well-documented diagnosis of the CHD type. We identified a series of repeating color doppler flow patterns seen in the four-chamber, three-vessel, and trachea views of the studied cases. Our observations could be developed into a diagnosis algorithm to orientate the examiner to the most likely type of CHD in individual cases.

Pathological Examination of the Late Embryonic Heart Using the Same 4-chamber and 3-vessel Planes Used in Fetal Echocardiography.

BACKGROUND/AIM: The incidence of early pregnancy loss widely varies according to age, being considerably higher in older women. Severe congenital malformations play an important role in pregnancy loss, having a high risk of recurrence. Congenital heart defects are the most common congenital abnormalities, thus the diagnosis of such malformations in aborted embryos is important for establishing both a possible cause for pregnancy loss and for correctly counseling the parents. Pathologic examination of the heart that is only a few millimeters in size, is very challenging. PATIENTS AND METHODS: A pathologic examination protocol using transverse microscopic sections at the level of the 4-chamber and 3-vessel planes is proposed for heart evaluation. RESULTS: Two 9-10 gestational weeks embryos were microscopically examined using transverse slides of the thorax. The 4-chamber and 3-vessel slides were analyzed and compared to 11-13 weeks ultrasound images of the 4-chamber and 3-vessel views from 10 cases. The pathologic examination provided a detailed view of the ventricles, atria and great vessels, sometime surpassing even the ultrasound examination that was performed at a later gestational age. CONCLUSION: We consider our proposed pathologic examination protocol feasible for evaluating normal heart structures and ruling out severe congenital heart disease.

Umbilical cord lactate compared with pH as predictors of intrapartum asphyxia.

Despite advances in fetal monitoring during labor, one of the most critical causes of neonatal death and neurologic injuries remains intrapartum asphyxia. Umbilical cord gases can be used to detect acidosis and fetal distress. We conducted a retrospective, multicenter study to evaluate umbilical cord blood pH and lactate as a mean of evaluating the degree of intrapartum hypoxia and also to establish which of the two is more reliable in predicting morbidity in term neonates. The present study utilized a total of 124 cases that met the criteria for intrapartum asphyxia and 150 normal term newborns that were randomly selected as case control. Both umbilical cord lactate and pH proved to be accurate predictors of neonatal morbidity caused by intrapartum hypoxia. Lactate proved to be superior to pH in predicting adverse neonatal outcome. The greatest sensibility and specificity in predicting intrapartum asphyxia were achieved in our study by using a cutoff value of 3.75 mmol/l for lactate and 7.24 for pH.

Impact of histological subtype on the response to chemoradiation in locally advanced cervical cancer and the possible role of surgery.

Cervical cancer is one of the most common cancers in women in developing countries, second only to breast cancer, with more than 450.000 new cases every year. Romania has the highest incidence of cervical cancer in Europe; more than four times the incidence found in Western Europe. Radiotherapy with or without chemotherapy is considered in most countries the gold standard for locally advanced cervical cancer. In Romania, if downstaging occurs after radiotherapy, adjuvant surgery is routinely performed. Thus, in the present study, we investigated the rate of residual cancer in patients with locally advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy and to determine the impact of tumor histological subtype on the chemoradiotherapy response. Of a total of 461 patients with locally advanced cervical cancer that underwent chemoradiotherapy and adjuvant surgery, 254 had a partial response defined as the presence of residual tumor at pathology examination. Depending on the histological subtype of the cervical cancer, partial response was obtained in 50.6% of squamous cell carcinoma cases and in 77.6% of adenocarcinoma or adenosquamous carcinoma cases. The present study demonstrated that cervical cancer patients with adenocarcinomas and adenosquamous carcinomas had a significantly poorer treatment response to chemoradiotherapy than those with squamous cell carcinomas. We consider that in such cases where residual tumor is present, adjuvant surgery is mandatory for improving the survival rates.

The wide spectrum of ultrasound diagnosis of holoprosencephaly.

AIM: Holoprosencephaly (HPE) is the most common brain malformation. A wide spectrum of anatomical variants are characterized by a lack of midline separation of the cerebral hemispheres. The aim of this study was to assess the ultrasound diagnostic criteria for HPE. MATERIAL AND METHOD: A database of 175 fetuses with central nervous system anomalies identified by ultrasound was collected retrospectively from 2006 to 2016 in this multicenter, retrospective, observational study. Among them 18 cases (10.2%) with HPE were identified. RESULTS: The prevalence of HPE was 2.5:10.000 with the sex distributionmale:female of 1:1.6. Six cases were alobar subtype, 3 were semilobar, 7 were lobar and 2 were middle interhemispheric variant. In the second trimester, we consider that the abnormal fusion of the lateral ventricles and the absence of the cavum septum pellucidum are the most important landmarks for HPE. Facial abnormalities varied considerably. CONCLUSION: This study illustrates the heterogeneity of HPE with different cerebral and facial appearances.

Alobar holoprosencephaly associated with a rare chromosomal abnormality: Case report and literature review.

RATIONALE: Holoprosencephaly is a structural malformation of the brain that results from the complete or incomplete noncleavage of the forebrain of the embryo into 2 hemispheres. We report a severe case of alobar holoprosencephaly diagnosed at 38 weeks, associated with cebocephaly, microcephaly, and craniosynostosis. PATIENT CONCERN: The main knowledge added by this case is the late ultrasound diagnosis and chromosomal analysis that revealed a very rare abnormality (45X/46,XX/47,XX) with mosaicism at chromosome 18. DIAGNOSES: Investigation of the mother revealed nothing remarkable from clinical point of view and on laboratory tests. Ultrasonography identified a fetal biometry appropriate for gestational age, except for the head biometry and abdominal circumference, that were appropriate for less than the fifth percentile. Microcephaly, a large midline monoventricle, absent midlinestructures, cleft lip, cebocephaly (hypotelorism, single-nostril nose), ethmocephaly (hypotelorism, interorbital proboscis) and craniosynostosis, were also present. Fetal magnetic resonance imaging of fetus revealed an absent midline structure, a central monoventricle, abnormal corpus calosum, and abnormal gyri. INTERVENTIONS: A cesarean section at 38 weeks was indicated for fetal bradycardia and a female baby was delivered, with Apgar score 6, weight 2290g. After birth, the diagnosis of the fetus confirmed holoprosencephaly with facial anomalies and demonstrated repeated tonic-clonic seizure, severe respiratory failure, cyanosis, decreased muscle tone, palor, and apnea. Laboratory examination of the newborn revealed acidosis and a prolonged of prothrombin time. The neonate was treated for severe respiratory distress syndrome, with immediate intubation and resuscitation. Vitamin K, fresh frozen plasma, and antibiotics were also administered. OUTCOMES: After delivery, exitus of the fetus occurred at 3 days and 18hours due to massive pulmonary hemorrhage. LESSONS: We described a case of alobar holoprosencephaly diagnosed at 38 weeks of gestation and associated with a rare chromosomal abnormality (45X/46,XX/47,XX) with mosaicism at chromosome 18. Emotional implications could have been less severe if the patient underwent regular ultrasonography allowing a diagnosis in the first or early second trimester.

Difficulties of clinical and histopathological diagnosis in advanced vulvar clear cell carcinoma.

Clear cell carcinoma (CCC) of the female genital tract usually arises in the ovary, endometrium, cervix and vagina. A rare site for CCC is the vulva, and moreover even rarer are the cases involving the Bartholin gland. A 54-year-old female was admitted for a 1.5×2 cm tumor at the level of the right Bartholin gland. The magnetic resonance imaging (MRI) exam revealed enlarged inguinal, pelvic and para-aortic lymph nodes but no other primary tumor. Microscopic examination revealed CCC. The tumor was positive for cytokeratin 7 (CK7), paired-box 8 (Pax8), napsin A and vimentin, negative for estrogen receptor (ER), progesterone receptor (PR), calretinin, cluster of differentiation 10 (CD10), carcinoembryonic antigen (CEA), p16 and p63. Also, p53 was expressed in 30-40% and Ki67 in 70% of the malignant cells. Given the clinical, imagistic, histological and immunohistochemical features of the tumor, we concluded that the tumor is a CCC of the Bartholin gland. Aim of the study is to signal a rare case of CCC of Bartholin gland. Since there are only two other cases reported in literature, the natural history and prognosis of the disease is not known, also there are no therapeutic guidelines regarding this rare tumor so appropriate treatment is uncertain. Therefore, it is important that new cases are reported for a better understanding of this rare condition. Bartholin gland carcinoma is a pathology quite rarely encountered in practice. The positive diagnosis is eminently histological and immunohistochemistry. Bartholin gland CCC is an extremely rare diagnosis with, to our knowledge, only two other cases reported in literature, but with a potential aggressive clinical behavior and poor outcome.

Antenatal diagnosis and prognostic factors of aneurysmal malformation of the vein of Galen: A case report and literature review.

RATIONALE: Vein of Galen aneurysmal malformation (VGAM) is a rare complex malformation of the cerebral vascular system consisting of arteriovenous shunts between the vein of Galen and the cerebral arteries. PATIENT CONCERNS: We present the case of a 31-year-old pregnant woman, para 1, gravida 1. DIAGNOSES: At 26 weeks' gestation who was examined for an anechoic mass on the cerebral median midline with color and pulsed Doppler. She presented with positive flow on the color and pulsed Doppler test, associated with hydrocephalus, cortical hypoplasia, cardiomegaly, jugular vein distension. INTERVENTIONS: No intervention for VGAM was done. OUTCOMES: This case of a VGAM was associated with negative prognostic factors. LESSONS: The ultrasound color Doppler together with the 3D power Doppler allowed reconstruction of the vascular connections and of the relationship of these with other anatomical structures, which contributed to establishing the prognosis.

Good Prognosis Went Badly: Fulminant Evolution of a 29-Year-Old Patient with Verrucous Carcinoma of the Cervix.

Verrucous carcinoma (VC) is a very rare variant of squamous cell carcinoma of the cervix, difficult to point out in histology because of its benign appearance. We present the case of a 29-year-old woman with a locally advanced cervical VC who underwent radiotherapy followed by radical hysterectomy. After local relapse and despite pelvic exenteration, her condition deteriorated. Treatment of choice in VC is surgery, because of the risk of anaplastic transformation under irradiation, raising the chances of distant spread and converting this rather benign-like type of cancer to an aggressive cancer.