Single Center Experience of Genetic Testing in Patients Undergoing Breast Cancer Treatment.

BACKGROUND: Breast cancer remains the most frequently diagnosed cancer in female population worldwide. However, germline mutations are responsible for a small proportion of these cases. The aim of our study is to assess how germline mutations influence the management and outcome of these patients taken into consideration both their cancer diagnosis and genetic assessment. METHODS: We performed a retrospective analysis in a women's single-center during a period of six years to assess the contribution of germline mutation in the treatment, prognosis and survival of breast cancer patients. Statistics were collected from both the patients' medical records and genetics department. RESULTS: From the total number of patients treated for breast cancer in our department between 2017 and 2022, 243 were eligible for genetic testing, comprising either BRCA1/2 or extended panel, taking into consideration their personal and family history. Of all subjects included in our study cohort, 5% were carriers of a pathogenic(P) or likely pathogenic(LP) variant of cancer susceptibility gene, of which 78% were diagnosed before the age of 50; triple negative disease was diagnosed in the majority of cases, and therefore, 62% of patients started treatment with systemic neoadjuvant chemotherapy and 32% of subjects underwent upfront surgery. Prophylactic surgery for contralateral breast and bilateral salpingo-oophorectomy was considered and performed for 20% of patients. Less than 2% of cases had metastatic disease and received PARP inhibitors, with excellent treatment response and a very low rate of mortality in the study group. CONCLUSION: Carriers of pathogenic variants with breast cancer diagnosis may have a greater benefit from a tailored approach, including both surgical and oncological treatment, with better long-term outcomes.

Evaluation of quality of life and socio-emotional impact of oncological treatment among patients with breast cancer.

Breast cancer is the most frequent cancer in women worldwide. Quality of life (QoL) is significantly affected by both surgical and oncological treatment. The aim of this study was to assess and compare QoL, resilience and depression scores among women who had breast cancer treatment. We assessed 170 patients diagnosed with breast cancer in a non-experimental, descriptive study through anonymized questionnaires from January to March 2024. Patients were invited to fill in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Breast Cancer Module (EORTC QLQ-BR23) questionnaire, the Depression Anxiety Stress Scale, the CD-RISC 10 questionnaire, and the MOS Social Support Survey. Clinical information and demographical data were obtained and statistical analysis was conducted to evaluate factors that affect QoL, resilience and depression scores. QoL was significantly influenced by chemotherapy and surgery. Women with higher resilience scores had lower anxiety and depression scores and reported a better QoL. Women with strong social support and high resilience reported a better QoL during and after breast cancer treatment. The results of our study show that breast cancer surgery and chemotherapy have an important impact on patients' QoL. Moreover, the results reflect the importance of both medical treatment and social support as resilience-building strategies in managing and improving the QoL of patients.

The Psychological Impact on Romanian Women Infected with SARS-CoV-2 during Pregnancy.

BACKGROUND: It is well-known that the uncertainty about the COVID-19 pandemic has an indirect negative impact on pregnant women's mental health, given the fact that pregnant women are more vulnerable emotionally and psychologically than non-pregnant women. The aim of this study was to evaluate the maternal psychological impact on Romanian women who were infected with SARS-CoV-2 during pregnancy and their concerns and to determine which are the best measures to prevent negative outcomes. METHODS: A 40-item questionnaire was created for data collection and was shared on social platforms (Facebook and Instagram) and also with obstetric communities between February 2021 and January 2023. Our cross-sectional survey recruited 317 Romanian pregnant women who suffered from SARS-CoV-2 infection. Among general questions about their life and pregnancy during the pandemic, the survey included questions about their SARS-CoV-2 infection during pregnancy, their concerns and how they perceived this period in order to evaluate their emotional status. RESULTS: Of 317 women recruited, 91% of them had a mild to moderate form of COVID-19, and 2% had serious symptoms. Only 9% of women were hospitalized, 4% of women considered that the SARS-CoV-2 infection affected their physical condition to a great extent, and 8% considered to be affected in terms of mental state to a great extent. The main negative feelings of pregnant women during the COVID-19 disease were the fear regarding the possibility of affecting the pregnancy and the concern for their life (51.4%). These increase the risk of developing anxiety or depression. Pregnant women who contracted SARS-CoV-2 infection faced negative feelings, especially those with a severe form of the disease or who recovered with difficulty after the disease. Patients who required hospitalization reported an impairment of the mental state to a great extent and to a very great extent with a frequency of approximately two times and four times higher than non-hospitalized patients, respectively (p < 0.05 and p < 0.001, respectively). Also, giving birth during SARS-CoV-2 and the difficulty of accessing medical services represented a high level of stress. Also, 47% of patients who reported difficulty accessing medical services during the illness evaluated their mental state significantly less favorably. CONCLUSION: Preventive measures are essential to minimizing the negative psychological impact of COVID-19 disease during pregnancy among pregnant women. The medical treatment of COVID-19 disease during pregnancy should be prioritized, but emotional and mental health support must also be provided.

Body Stalk Anomaly.

Abdominal wall defects encompass three primary classifications: gastroschisis, omphalocele and anomalies resembling body stalk. Potential causative factors include early amnion rupture, amniotic bands, vascular disruptions or abnormal folding of the embryo. The prevalence of these defects stands at 1 in 14,000 live births. Body stalk anomaly is characterized by a substantial abdominal defect coupled with spine and limb anomalies, along with a very short or absent umbilical cord. We present a case of a rare abdominal defect known as body stalk anomaly, the most severe form of this spectrum of diseases. The diagnosis of this anomaly was established during the first trimester of pregnancy. Subsequently, the patient opted for pregnancy termination and chose not to undergo genetic testing. The anatomo-pathological results confirmed the findings. Body stalk anomaly is not compatible with life; therefore, early identification and understanding the clinical implications of this rare anomaly for informed decision-making in prenatal care are very important.

Eugen Bogdan Aburel, a pioneer of fertility sparing surgery.

Eugen Bogdan Aburel was pioneer of the fertility sparing surgery in early cervical cancer in young women desiring to preserve their childbearing potential. He graduated in Romania but started specializing in obstetrics and gynecology in Paris, where he had the chance to work with the most prominent professors of the time and do research at Sorbonne, the most famous French higher education institution. Most of his discoveries date from the time he spent in Paris hospitals, proving that a good medical school can generate remarkable physicians. The fertility sparing surgery he created after returning to Romania did not have the same chance to be known and spread to the international medical world because of the Cold War isolation, Romania belonging to the Eastern Communist bloc. However, his pioneering work in this field of surgery is fully recognized today.

Prenatal Ultrasound Diagnosis of Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is a very rare vascular malformation syndrome also referred to as a capillary-lymphatic-venous malformation with unknown aetiology. The aim of our paper is to highlight interesting images, regarding a rare case of foetal Klippel-Trenaunay syndrome diagnosed prenatally in our department and confirmed postnatally with a favourable evolution during the gestation and neonatal periods. This case was diagnosed at 26 weeks gestation and characterised through ultrasound by the presence of superficial multiple cystic structures of different sizes spreading over the left leg with hemihypertrophy and reduced mobility. The cystic lesions were spreading to the left buttock and the pelvic area. The right leg and upper limbs had normal appearance with good mobility. There were no signs of hyperdynamic circulation or foetal anaemia, but mild polyhydramnios was associated. The ultrasound findings were confirmed postnatally, the left leg presented multiple cystic lesions and port wine stains, and there was hypertrophy and fixed position, with favourable evolution at 6 months of life, when the size of the lesions began to decrease and the mobility of the leg improved.

Sonographic Detection of Fetal Cholelithiasis.

Fetal biliary lithiasis is a benign condition characterized by the presence of gallstones in the gallbladder of a developing fetus. It is typically detected incidentally during a routine obstetric echography. The incidence of this condition varies from 0.03% to 2.3%. In most cases, fetal cholelithiasis resolves spontaneously and has an excellent prognosis. However, there are certain risk factors that may contribute to its development. Maternal factors that increase the risk of fetal cholelithiasis include placental abruption, elevated estrogen levels, narcotic use, diabetes, enteral nutrition, and specific medications, such as ceftriaxone, furosemide, and prostaglandin E2. Fetal factors that can contribute to the condition include Rhesus or ABO blood group incompatibility, congenital anomalies affecting the cardiovascular, gastrointestinal, or urinary systems, twin pregnancies with the fetal demise of one twin, genetic anomalies such as trisomy 21, chromosomal aberrations, cystic fibrosis, growth restriction, oligohydramnios, hepatitis, or idiopathic causes. Usually, the gallstones spontaneously resolve before or after birth without requiring specific treatment. However, in rare instances, complications can arise, such as the formation of biliary sludge, inflammation of the gallbladder (cholecystitis), or obstruction of the bile ducts. If complications occur or if the gallstones persist after birth, further evaluation and management may be necessary. Treatment options can include medication, minimally invasive procedures, or, in severe cases, surgical removal of the gallbladder.

Skeletal Dysplasia: A Case Report.

This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis-a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy.

Umbilical Cord Prolapse-Interesting CTG Traces.

Umbilical cord prolapse can be a life-threatening obstetrical event involving the fetus due to sudden oxygenated blood flow obstruction. These types of events most often happen in labor and are associated with obstetric maneuvers. Rarely, a clinical examination can diagnose the condition, but the situation is usually detected secondary to an abnormal cardiotocography trace. We present several clinical cases where a CTG trace was used to infer umbilical cord prolapse.

Microduplication 3p26.3p24.3 and 4q34.3q35.2 Microdeletion Identified in a Patient with Developmental Delay Associated with Brain Malformation.

Microdeletions and microduplications are involved in many of prenatal and postnatal cases of multiple congenital malformations (MCM), developmental delay/intellectual disability (DD/ID), and autism spectrum disorders (ASD). Molecular karyotyping analysis (MCA), performed by DNA microarray technology, is a valuable method used to elucidate the ethology of these clinical expressions, essentially contributing to the diagnosis of rare genetic diseases produced by DNA copy number variations (CNVs). MCA is frequently used as the first-tier cytogenetic diagnostic test for patients with MCM, DD/ID, or ASD due to its much higher resolution (≥10×) for detecting microdeletions and microduplications than classic cytogenetic analysis by G-banded karyotyping. Therefore, MCA can detect about 10% pathogenic genomic imbalances more than G-banded karyotyping alone. In addition, MCA using the Single Nucleotide Polymorphism-array (SNP-array) method also allows highlighting the regions of loss of heterozygosity and uniparental disomy, which are the basis of some genetic syndromes. We presented a case of a five-year-old patient, with global development delay, bilateral fronto-parietal lysencephaly, and pachygyria, for which MCA through SNP-Array led to the detection of the genetic changes, such as 3p26.3p24.3 microduplication and 4q34.3q35.2 microdeletion, which were the basis of the patient's phenotype and to the precise establishment of the diagnosis.

Herlyn-Werner-Wunderlich Syndrome: Case Report and Review of the Literature.

Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital malformation of the urogenital tract involving both the müllerian and the wolffian ducts, and it consists of the association of didelphys uterus, ipsilateral obstructed hemivagina, and ipsilateral kidney agenesis. Its etiology is related to the abnormal development of two embryonic structures-mesonephros and paramesonephros-although its precise mechanism is not known, but theories involving signaling molecules and gene expression are studied for potential explanations. Because of its rarity, there is limited literature on this subject. We present a case diagnosed in our department and elaborate on management. In HWW syndrome, symptoms appear after menarche and include pelvic pain, with progressive intensity due to the developing of hematocolpos. Menstruation may be present or absent depending on the type of anomaly. The use of magnetic resonance imaging (MRI) is the most recommended method of investigation since, in most cases, at this age, sexual life has not started yet and transvaginal ultrasound cannot be used. Surgical treatment in our case consisted of an exploratory laparoscopy followed by a vaginal surgical approach to resect the vaginal septum of the obstructed hemivagina.

Ovarian Germ Cell Tumors: Pictorial Essay.

Ovarian germ cell tumors of the ovary represent a histologically heterogenous group of tumors with a high incidence at reproductive age. Patients with this pathology are very often young women with amenorrhea. The aim of this article is to present a pictorial essay of this rare pathology and to promote a national tumor registry and protocol. The treatment is individualized according to age, and fertility-sparing surgery is the actual standard of surgical treatment for young patients in early stage of the disease.

Ultrasound Appearance of Fetal Posterior Fossa and a Case Report of Prenatal Diagnosis of Dandy-Walker Malformation.

Prenatal sonographic assessment of the posterior fossa in the mid-sagittal plane at 11-14 weeks' gestation has been highlighted as an essential diagnostic step by the current literature. This approach is used for the early detection of open spina bifida during the first trimester by analyzing the three spaces of the posterior fossa: brain stem, the fourth ventricle and cisterna magna. Abnormal size of fetal posterior fossa spaces is an important sign in the diagnosis of fetuses with central nervous system malformation and needs to be submitted for differential diagnosis when any alterations are observed. Among them, Dandy-Walker malformation is one of the major causes of congenital hydrocephalus, being a rare condition, with poor-prognosis, manifested by enlarged posterior fossa. On the basis of available evidence, the assessment of the fetal posterior cranial fossa is feasible from 11 to 14 weeks gestational age and it is believed that abnormal appearance of the posterior fossa at this stage of pregnancy could improve early detection of Dandy-Walker malformation by prompting an early second trimester ultrasound evaluation.

Pulmonary Alveolar Proteinosis and Pregnancy: A Review of the Literature and Case Presentation.

Pulmonary Alveolar Proteinosis (PAP) is a rare, usually autoimmune, disease, where surfactant accumulates within alveoli due to decreased clearance, causing dyspnea and hypoxemia. The disease is even more rare in pregnancy; nevertheless, it has been reported in pregnant women and can even appear for the first time during pregnancy as an asthma-like illness. Therefore, awareness is important. Similarly to many autoimmune diseases, it can worsen during pregnancy and postpartum, causing maternal and fetal/neonatal complications. This paper offers a narrative literature review of PAP and pregnancy, while illustrating a case of a pregnant patient with known PAP who developed preeclampsia in the third trimester but had an overall fortunate maternal and neonatal outcome.

Risk of Subsequent Hysterectomy after Expectant Management in the Treatment of Placenta Accreta Spectrum Disorders.

Management strategies for pregnancies with abnormal adherence/invasion of the placenta (placenta accreta spectrum, PAS) vary between centers. Expectant management (EM), defined as leaving the placenta in situ after the delivery of the baby, until its complete decomposition and elimination, has become a potential option for PAS disorders in selected cases, in which the risk of Caesarean hysterectomy is very high. However, expectant management has its own risks and complications. The aim of this study was to describe the rates of subsequent hysterectomy (HT) in patients that underwent EM for the treatment of PAS disorders. We reviewed the literature on the subject and found 12 studies reporting cases of HT after initial intended EM. The studies included 1918 pregnant women diagnosed with PAS, of whom 518 (27.1%) underwent EM. Out of these, 121 (33.2%) required subsequent HT in the 12 months following delivery. The rates of HT after initial EM were very different between the studies, ranging from 0 to 85.7%, reflecting the different characteristics of the patients and different institutional management protocols. Prospective multicenter studies, in which the inclusion criteria and management strategies would be uniform, are needed to better understand the role EM might play in the treatment of PAS disorders.

Incidence of Emergency Peripartum Hysterectomy in a Tertiary Obstetrics Unit in Romania.

Background and Objectives: Emergency peripartum hysterectomy (EPH) is a life-saving surgical procedure performed when medical and surgical conservative measures fail to control postpartum hemorrhage. The objective of this study was to estimate the incidence of EPH and to determine the factors leading to this procedure and the maternal outcomes. Materials and Methods: A retrospective cohort study with all cases of EPH performed at Filantropia Clinical Hospital in Bucharest between January 2012 and May 2021. Results: There were 36 EPH, from a total of 36,099 births recorded. The overall incidence of EPH was 0.99 per 1000 deliveries, most cases being related to placenta accreta spectrum disorder and uterine atony. Conclusions: Peripartum hysterectomy is associated with an important maternal morbidity rate and severe complications. Efforts should be made to reduce the number of unnecessary cesarean deliveries.

Severe Neonatal Anemia Due to Spontaneous Massive Fetomaternal Hemorrhage at Term: An Illustrative Case with Suspected Antenatal Diagnosis and Brief Review of Current Knowledge.

Fetomaternal hemorrhage is defined as transfer of fetal blood into placental circulation and therefore into maternal circulation during pregnancy, and represents an important contributor to intrauterine fetal demise and neonatal death. The condition is rarely diagnosed prenatally because clinical findings are often nonspecific, and it is unpredictable. In this paper we present an illustrative case of massive spontaneous fetomaternal hemorrhage where the diagnosis was highly suspected antenatally based on maternal reported reduced fetal movements, abnormal suggestive cardiotocographic trace, and increased peak systolic velocity in the fetal middle cerebral artery. We discuss obstetrical and neonatal management and review the current knowledge in the literature. Maintaining a high index of suspicion for this condition allows the obstetrician to plan for adequate diagnostic tests, arrange intrauterine treatment or delivery, and prepare the neonatal team.

The Relationship between the Infertility Specialist and the Patient during the COVID-19 Pandemic.

The doctor-patient relationship is fundamental in the treatment of infertility, due to the emotional implications of fertilization procedures. However, insufficient data are available specifically for this relationship. The general objective of the study is to establish the associations between the fundamental concepts that define the doctor-patient relationship: communication, empathy, trust, collaboration, compliance and satisfaction. A cross-sectional study was conducted between May and June 2020 and followed the methods of a quantitative analysis, collecting the data using questionnaires. The research plan was specific to path analysis with the mediation effect, in which the hypotheses were tested. The research group consisted of 151 women diagnosed with infertility, voluntarily recruited through online support communities. Findings demonstrate that affective empathy mediates the relationship between communication and trust in the doctor. In conclusion, this study draws attention to the importance of basic concepts in the relationship of infertility specialists with infertile patients. Thus, it is necessary for health care providers in assisted human reproduction to participate in programs for the continuous training of empathic communication skills, given the sensitivity of this diagnosis.

Counseling Process in Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is a heterogenous group of intraductal proliferations, without a known natural history and predictability and without being considered an obligatory precursor of invasive ductal cancer. Lack of biological markers of predictability makes its evolution uncertain. Because DCIS is not an obligatory precursor of invasive breast cancer, counselling will not be made like in invasive cancer. Counselling must recognize the uncertainty of progression toward invasive disease and every patient must be correctly and empathically informed so that she is as involved as possible in the decision-making process.

Ductal Carcinoma In Situ - Quo Vadis?

The introduction of mammographic screening in the early 1980's was associated, in the three following decades, with a dramatic increase in the detection of ductal carcinoma in situ (DCIS), pathology rarely detected before, on surgical specimen, at the periphery of an invasive cancer (1,2,3). It is estimated that in the United States the incidence of DCIS, each year, varies between 18 to 25% of the total number of newly diagnosed breast cancers (4,5). Ductal carcinoma in situ belongs, genetically and pathomorphologically, to a heterogenous group of preinvasive neoplastic lesions characterized by clonal proliferation of malignant cells limited to the lumen of breast ducts. It has not a known natural history and its phenotypical spectrum is wide, varying from a slowly evolving disease to a fast growing one, invading the surrounding stroma and even metastasizing to distant sites (6). In the absence of reliable prognostic markers, most of patients are submitted to invasive treatments consisting mainly in surgery, alone or associated with radiation and endocrine therapy (7). Molecular subtyping has improved the understanding of breast cancer biology and its possibilities for evolution and have provided the tools to design a more personalized treatment (8). In the absence of reliable molecular markers clinical management of patients with DCIS is based on patient's option and tumor characteristics. Based on the knowledge of today, DCIS could be used to exemplify the notions of overdiagnosis and overtreatment. The final goal of the treatment of DCIS is to prevent invasive breast cancer recurrence. Mortality rate associated with DCIS is very low, being estimated at 1-2 % at 10 years, while patients with DCIS treated by wide local excision with or without radiation may have a local recurrence rate of 5 to 30% and half of these present as an invasive cancer. Today's clinicians are not able to predict the risk of progression for a DCIS diagnosed by biopsy, but neither the risk of local recurrence, as an invasive cancer, of DCIS treated by conservative surgery with or without radiation (9). Progression to invasive cancer is difficult to be predicted as the disease is highly heterogenous. Because of these uncertainties, it is highly important to carefully inform the patient and engage her in the treatment decision process (10). There is a trend for de-escalation of treatment for DCIS. A study comparing two groups of patients with pure DCIS was conducted: one with standard care and the other under active surveillance (11). The main outcome was the probability to die from breast cancer at 10 years after the diagnosis. The mortality risk from breast cancer is higher for younger women, than the older ones, under active surveillance. Women over the age of 70 years, have many comorbidities that could induce the risk of dying, regardless of DCIS treatment decision. This study suggested that active surveillance could be a reasonable option for certain category of patients. This attitude is not without risks. A patient with DCIS on core needle biopsy could hide an invasive cancer in 25% of cases (12). Today, there are four randomized control trials of active surveillance offered to patients with low-grade DCIS: LORD (LOw Risk DCIS), COMET (Comparison of Operative to Monitoring and Endocrine Therapy), LORIS (LOw RISk DCIS) and LORETTA (10,13-16). Non-surgical approaches are of two types: active surveillance alone or associated with hormone therapy. There are some differences between the trials. While in LORD and LORIS trials the study arms are represented by active surveillance only, hormone therapy is an option in COMET trial and mandatory in the single arm trial LORETTA. The aim of these studies is to examine the safety and the effectiveness of active surveillance compared with surgical management for low-risk DCIS. The results of these trials are awaited with great interest. Patients with ductal carcinoma in situ need special counseling. To talk about "a good" cancer or even no cancer and to recommend as treatment a mastectomy is highly confusing. The language used by all members of the team must be unitary, removing the anxiety and helping patients to make the best decision. This special issue is a great opportunity to have the opinions of highly respected international specialists in the field for a comprehensive review of DCIS of the breast.