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.

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.

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.

Cervical cancer in Eastern Europe: review and proceedings from the Cervical Cancer Research Conference.

Cervical cancer is the third most common cancer among women worldwide, with a disproportionately high burden of disease in less-developed regions of the world. The Cervix Cancer Research Network was founded by the Gynecologic Cancer InterGroup with a mission to improve outcomes in cervical cancer by enhancing international access to clinical trials, specifically in under-represented, underdeveloped areas. The Cervix Cancer Research Network held its third international educational symposium in Bucharest in 2018 and is the subject of this report. The purpose of this symposium was to advance the international understanding of cervical cancer treatment patterns, to foster recruitment to Cervix Cancer Research Network clinical trials, and identify key Cervix Cancer Research Network clinical trial concepts to improve cervical cancer care worldwide.

Diagnosis and Management of Cesarean Scar Pregnancy and Placenta Accreta Spectrum: Case Series and Review of the Literature.

With an increased cesarean delivery rate, the incidence of abnormal placentation is steadily rising, and it is estimated to be around 1.7 per 1000 pregnancies for cesarean scar pregnancy and 1 per 500 pregnancies for placenta accreta spectrum disorder. Current evidence considers cesarean scar pregnancy and placenta accreta spectrum as being the same condition, with different aspects, of the same spectrum, having higher risks with advancing gestation. We present 7 cases, diagnosed and managed in our hospital, at different gestational ages. Early diagnosis is essential for appropriate counseling and subsequent management, and an ultrasound examination is the reference standard for diagnosis. Screening for an abnormally implanted placenta in the first trimester of pregnancy might improve the perinatal outcome and reduce maternal morbidity and mortality.

Rosai-Dorfman Disease: Breast Involvement-Case Report and Literature Review.

Background and objectives: Rosai-Dorfman disease (RDD) is a type of histiocytosis that usually appears in young adults or children as bilateral cervical lymphadenopathy, but extranodal involvement in not uncommon. Although the pathogenesis is not entirely elucidated, recent studies showed a possible neoplastic process. Materials and methods: Our manuscript presents a rare case of Rosai-Dorfman disease of the breast, the management of this rare case, and a literature review. There are few cases reported of RDD of the breast (around 90 globally reported cases); the data is poor, and the management not yet standardized for these cases. The case reported here shows the importance of correct breast investigation, breast imaging, and ultrasound-guided biopsy that provided an accurate diagnosis and guided further management. Results: Although RDD of the breast was rarely presented as bilateral disease in other case reports, our case showed bilateral breast disease with the suspicion of breast cancer on imaging. Pathology and immunohistochemistry were of critical importance and showed a specific pattern for histiocytosis. A multidisciplinary approach was taken into consideration for these cases in order to establish the approach. Some patients underwent surgery, but watchful waiting and close follow-up were the preferred approach. Conclusions: RDD of the breast is a rare form of histiocytosis, with fewer than 100 globally published cases. Although the management of this disease is not established yet by guidelines, a follow-up approach should be enough for these patients, and surgery might be overtreatment. Mortality from RDD is very low due to comorbidities. A multidisciplinary team decision is important, and abstinence might significantly benefit these patients.

Absence of Wharton's Jelly at the Abdominal Site of the Umbilical Cord Insertion. Rare Case Report and Review of the Literature.

Wharton's jelly is a specialized connective tissue surrounding and protecting umbilical cord vessels. In its absence, the vessels are exposed to the risk of compression or rupture. Because the condition is very rare and there are no available antepartum investigation methods for diagnosis, these cases are usually discovered after delivery, frequently after in utero fetal demise. We report the fortunate case of a 29-year-old nulliparous woman, with an uncomplicated pregnancy, admitted at 39 weeks in labor where a persistently abnormal cardiotocographic trace led to delivery by cesarean section of a healthy 3500 g newborn. After delivery, a Wharton's jelly anomaly was identified at the abdominal umbilical insertion (umbilical cord vessels, approximately 1 cm in length, were completely uncovered by Wharton's jelly), which required surgical thread elective ligation. In the presence of a persistently abnormal CTG trace, in a pregnancy with no clinical settings suggestive of either chronic or acute fetal hypoxemia, the absence of Wharton's jelly should be taken into consideration in the differential diagnosis.

Malignant Phyllodes Tumor of the Breast and Pregnancy: A Rare Case Report and Literature Review.

Phyllodes Tumor (PT) is a rare fibroepithelial breast tumor that can behave differently depending on its biologic features. Traditionally, PTs are classified by their histologic features into benign, borderline, and malignant. In most cases that were reported, all PTs may recur, but only the borderline and malignant PT can metastasize. PT usually occurs as a breast lump or accidental finding on ultrasound (US) examination. The clinical features include a well-defined breast mass, regular or lobulated. The diagnosis is based on the integration of morphology features, but remains challenging, particularly in the distinction from fibroadenomas. We report a case of a 36-year-old patient who presented for a voluminous breast mass, rapidly growing in the past 3-4 months. At presentation, the patient was 19 weeks pregnant. The breast tumor had the clinical and US aspect of PT. A core needle biopsy was obtained, confirming a benign PT, and local excision was performed with no postoperative complications. The final pathology report showed a borderline PT with close resection margins of 1 mm. Immunohistochemistry (IHC) established the diagnosis of malignant PT with heterologous sarcomatous differentiation. The case was discussed in the multidisciplinary tumor board (MDT) and mastectomy was recommended. The patient fully consented but refused surgery at 25 weeks' gestation, fearing premature delivery. The right breast was closely monitored by US, and at 9 weeks after the first surgery, signs of local recurrence were detected. At 35 weeks' gestation, right mastectomy was performed, with no perioperative complications. The pregnancy was closely followed up and no complication were found. The final pathology report describes multiples PT recurrences with heterologous sarcomatous differentiation. The pregnancy outcome was uneventful, and the patient delivered a healthy child vaginally at term with no peripartum complication. Postpartum, a computer tomography (CT) examination of the head, thorax, abdomen and pelvis was performed, with no evidence of metastases. Adjuvant chemotherapy and radiotherapy completed the treatment. The follow-up and CT scan showed no metastases or further recurrence 4 years after diagnosis. In conclusion, diagnosis of PT can be difficult, especially because of the easy confusion with fibroadenoma of the breast. There are rare cases when a pathology exam needs further assessment and IHC is recommended for accurate diagnosis. Although malignant PT is rare and accounts for <1% of all breast cancers, the diagnosis and treatment that are recommended are based on the reported cases. Moreover, when complete surgical excision is achieved, the rates of recurrence and distant metastases are low, and adjuvant therapy might not be necessary.

Screening for Gestational Diabetes during the COVID-19 Pandemic-Current Recommendations and Their Consequences.

Gestational diabetes mellitus (GDM) is recognized as one of the most common medical complications of pregnancy that can lead to significant short-term and long-term risks for the mother and the fetus if not detected early and treated appropriately. Current evidence suggests that, with the use of appropriate screening programs for GDM, those women diagnosed and treated have reduced perinatal morbidity. It has been implied that, when screening for GDM, there should be uniformity in the testing used and in further management. This paper summarizes and compares current screening strategies proposed by international bodies and discusses application in the context of the COVID-19 pandemic.

Fetal Surveillance in Pregnancies with Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune condition, that commonly impacts adult women of reproductive age. Myasthenia gravis in pregnancy is rare, but the incidence is higher in different geographical areas. Pregnancies in mothers with MG can have an unfortunate outcome. Acetylcholine receptor antibodies may pass into the fetal circulation and can affect the fetal neuromuscular junction, generating transient MG or even fetal arthrogryposis. The 2016 and 2021 International Consensus Guidance for Management of Myasthenia Gravis issued by Myasthenia Gravis Foundation of America is lacking in recommendation for fetal surveillance for pregnancies in women with MG. The aim of this paper is to highlight fetal and neonatal complications in mothers with MG and to offer antenatal care insights. Close maternal and pregnancy monitoring can improve pregnancy outcome. Patients with MG should be encouraged to conceive, to avoid triggers for exacerbations of the disease during pregnancy and a multidisciplinary team should be established to ensure the optimal support and therapy.

Myelomeningocele Surgery over the 10 Years Following the MOMS Trial: A Systematic Review of Outcomes in Prenatal versus Postnatal Surgical Repair.

Background and Objectives: Myelomeningocele is the most severe form of spina bifida, a congenital neural tube defect arising from an incomplete neural tube closure during early development with damage worsening with advancing gestational age. The Management of Myelomeningocele Study (MOMS) Trial proved that surgery performed before 26 weeks of gestation significantly improved the prognosis, significantly changing treatment paradigms. This article aims to provide a review of the changes and updates in spina bifida repair over the 10-year period following the MOMS Trial. Material and methods: We performed a systematic review in the PubMed and Cochrane databases as well as a hand-search of high-impact journals using the reference list of all identified articles, searching for randomized controlled trials and observational studies. Results: We identified 27 articles published between 2011 and 2021 that fulfilled the inclusion criteria and review them in the present study. Conclusions: With growing experience and with the improvement of prenatal open and fetoscopic techniques, the outcome of SB-associated conditions could be improved and the risks to both the mother and the fetus reduced. A continuous follow-up of the treated infants and further randomized trials are essential to study the complications and advantages or disadvantages of any given treatment strategy.

Secondary Amenorrhea and Infertility Due to an Inhibin B Producing Granulosa Cell Tumor of the Ovary. A Rare Case Report and Literature Review.

Granulosa cell tumor of the ovary (GCT) is a rare ovarian tumor with nonspecific symptoms. Studies reported that GCT are usually secreting estrogens and inhibins, especially inhibin B. It is considered that, in premenopausal women, irregular menses or secondary amenorrhea may be an early symptom of GCT and, in postmenopausal women, the most common manifestation is vaginal bleeding. Additionally, endometrial abnormalities can be associated due to estrogenic secretion. At reproductive age, high levels of inhibin, lead to low levels of FSH and secondary amenorrhea causing infertility. At times, increased levels of LH in women with GCT are observed and the pathogenesis is still unclear. Therefore, inhibin B level can differentiate GCT from other causes of secondary amenorrhea. We report the case of a 26-year-old nulliparous, women who presented in our clinic with secondary infertility lasting longer than 2 years, secondary amenorrhea, polycystic ovarian syndrome, and suspicion of right ovarian endometrioma on CT scan. The ultrasound examination revealed that the right ovary was transformed in an anechoic mass with increased peripheral vascularity having a volume of 10 cm3. This patient had high serum levels of inhibin B and LH but normal levels of FSH and estradiol. The preliminary diagnosis of granulosa cell tumor of the ovary was made. After counseling, the informed consent for treatment was obtained and the patient agreed to undergo surgery. An uneventful laparoscopy was performed with right oophorectomy and multiple peritoneal sampling. The histological diagnosis confirmed adult GCT limited to right ovary, with negative peritoneal biopsies (FIGO IA). After surgery the patient recovered fully and had normal menstrual cycles with normal serum levels of hormones. Two months later she conceived spontaneously and had an uneventful pregnancy. In conclusion, for cases with secondary amenorrhea, the evaluation of inhibin B level is essential. Elevated inhibin B level may be a sign for the presence of an unsuspected tumor. With early diagnosis and treatment, the prognosis is generally good and the fertility may be preserved, especially in young patients with GCT.

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.

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.

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.

Follow-up after Ductal Carcinoma In Situ Treatment.

Follow-up after ductal carcinoma in situ (DCIS) treatment is a matter of debates and a strategy has not yet been adopted. The current follow-up strategy is not distinguished from that of invasive breast cancers. Although in recent years DCIS is seen as a distinguished category of breast cancer, the follow-up strategy does not reflect this new paradigm. It continues to use the same strategy like in invasive breast cancer and practices differ widely worldwide or even in the same country. A consensus is needed to keep safety of patients and save costs without compromising the outcome.

Sentinel Lymph Node Biopsy in Breast Cancer. Principle, Difficulties and Pitfalls.

Sentinel Lymph node biopsy (SLNB) represents the standard approach in a newly diagnosed breast cancer for axillary staging in cases of clinical node negative. This represents a major prognostic factor and the biopsy of sentinel lymph node for early breast cancer is used as guidance in surgical and oncological treatment. Although for many decades, axillary lymph node dissection was the standard approach for breast cancer treatment and staging, this pathway was abandoned due to significant risk of lymphedema, infection, nerve and vessels injury or dysfunction of the shoulder. Therefore, significant improvement in the quality of life was seen for patients diagnosed with early breast cancer after SLNB was introduced as standard. The principle of SLNB is based on the hypothesis that tumor drains in the lymphatic system in an orderly manner and if the first lymphatic station is clear of disease, it is highly unlike that the tumor has spread further above. We present in our paper the indications with principles and difficulties in identification of sentinel node.

Diagnosis of Fetal Structural Anomalies at 11 to 14 Weeks.

OBJECTIVES: To assess the performance of first-trimester ultrasound (US) in identifying major fetal structural abnormalities in an unselected population. METHODS: We conducted a retrospective analysis of all pregnancies that underwent the 11- to 14-week scan in the Fetal Medicine Department of Filantropia Hospital in Bucharest, which were prospectively examined within our screening program. The purpose of the first-trimester US was to evaluate the risk for chromosomal abnormalities and to conduct fetal anatomic examination using a detailed protocol. RESULTS: Our population consisted of 7480 pregnant patients (7576 fetuses). The follow-up was completed for 6045 patients (6114 fetuses). The prevalence of major structural anomalies was 1.89%. In the first trimester, we identified 79% of all major structural anomalies. The highest detection rates were achieved for abdominal wall defects (100%), major central nervous system anomalies (88%), cardiac defects (74%), and skeletal anomalies (71%). The nuchal translucency was increased in 35% of the cases with structural anomalies, and 95% of these were diagnosed in the first trimester. Seventy percent of the patients who presented with structural anomalies and a normal nuchal translucency were diagnosed in the first trimester. CONCLUSIONS: Our results emphasize the importance of performing a detailed US examination at 11 to 14 weeks' gestation in identification of fetal structural defects.

Axial Torsion and Infarction of Meckel\'s Diverticulum in the 3rd Trimester of Pregnancy.

Meckel's diverticulum is a congenital anomaly which can become complicated or remain asymptomatic throughout life. During pregnancy, however, diverticulum infection could become a serious complication. Diverticulum necrosis and perforation are complications that increase morbidity in pregnancy, both maternal and fetal. The rarity of the condition and the maternal physiological changes in pregnancy make the diagnosis difficult. We present the case of a Meckel's diverticulum gangrene in third trimester pregnancy, atypical case due to advanced pregnancy where the risk-benefit balance was carefully evaluated on one hand because of the risk of infection associated with expectant management and on the other hand the risk and complications of iatrogenic preterm premature birth. The outcome was favorable for both mother and newborn.