Update on the Use of Nanocarriers and Drug Delivery Systems and Future Directions in Cervical Cancer.

Cervical cancer represents a major health problem among females due to its increased mortality rate. The conventional therapies are very aggressive and unsatisfactory when it comes to survival rate, especially in terminal stages, which requires the development of new treatment alternatives. With the use of nanotechnology, various chemotherapeutic drugs can be transported via nanocarriers directly to cervical cancerous cells, thus skipping the hepatic first-pass effect and decreasing the rate of chemotherapy side effects. This review comprises various drug delivery systems that were applied in cervical cancer, such as lipid-based nanocarriers, polymeric and dendrimeric nanoparticles, carbon-based nanoparticles, metallic nanoparticles, inorganic nanoparticles, micellar nanocarriers, and protein and polysaccharide nanoparticles. Nanoparticles have a great therapeutic potential by increasing the pharmacological activity, drug solubility, and bioavailability. Through their mechanisms, they highly increase the toxicity in the targeted cervical tumor cells or tissues by linking to specific ligands. In addition, a nondifferentiable model is proposed through holographic implementation in the dynamics of drug delivery dynamics. As any hologram functions as a deep learning process, the artificial intelligence can be proposed as a new analyzing method in cervical cancer.

New approaches in ovarian cancer based on genetics and carcinogenesis hypotheses (Review).

Ovarian cancer is the leading cause of death among gynecological malignancies and its incidence is rising in the last decades especially in developed countries. High-grade serous ovarian cancer (HGSOC) represents 70% of ovarian cancers. Oral contraceptive use and salpingo-oophorectomy or salpingectomy are well known protective factors against development of ovarian cancer. Identification of specific mutations associated with a high risk of developing ovarian cancer, especially BRCA1/2 mutation and TP53 mutations, has paved the way for implementation of new strategies for early diagnosis and therapy. Hereditary forms of ovarian cancer account for 5-10% and have BRCA1/2 gene mutations or TP53 mutations. BRCA1/2 gene mutations appear in 22% of HGSOC and are associated with the defective homologous repair (HR)/DNA repair pathway. Genetic testing in ovarian cancer is important for risk assessment and therapeutic options. Although 'universal genetic testing' is not recommended yet, the procedure remains highly recommended in women with high risk. Genes involved in the development of ovarian cancer as TP53 may be targeted by gene therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors may enhance the cytotoxic effect of DNA-damaging chemotherapy, and induce synthetic lethality in cases with BRCA1/2 mutations. Other strategies are designed to target pathways driven by various gene mutations, including the use of tyrosine kinase inhibitors in low-grade serous ovarian cancer (LGSOC), or the use of drugs, which target growth factors, or epigenetic events including methylation, and acetylation of genes. The tubal involvement in ovarian carcinogenesis provides an important tool for the clinician to implement risk-reducing strategies including salpingo-oophorectomy or salpingectomy in high-risk cases at appropriate ages.

A rare complication of uterine leiomyomata: Severe haemoperitoneum caused by the rupture of an overlying subserosa variceal vein: A case report.

The rupture of a subserosa variceal vein overlying a uterine myoma is a rare complication and a less common cause of gynecologic haemoperitoneum. The literature data are scarce regarding this condition and less than 100 cases have been reported (including those occurring during pregnancy). The present case is of a 48-year-old woman, with a history of asymptomatic uterine myoma, who was hospitalised for severe abdominal pain with sudden onset and signs of hypovolemic shock. The emergency conventional imaging exams confirmed the diagnosis of uterine myoma and haemoperitoneum, but did not reveal the source of bleeding. The cause of haemoperitoneum was detected by means of emergency laparotomy. In order to obtain quick hemostasis, in the settings of a rapid deteriorating hypovolemic shock, a supracervical hysterectomy was performed. The aim of the article is to raise awareness to gynecologists regarding this extremely rare life-threatening complication of the most common benign tumor of the uterus.

A Rare Cause of Massive Hematuria: Placenta Percreta With Bladder Invasion.

BACKGROUND/AIM: Placenta percreta is a rare event, but it poses serious problems due to potential hemorrhagic events. We report a particular case of placenta percreta with massive hematuria due to maternal bladder invasion, and describe the surgical protocol performed that resulted in an excellent outcome. CASE REPORT: A 33-year-old patient, at 27th weeks gestational age, presented in the emergency room of the Urology Department with urinary blood clot acute retention, because of massive hematuria from a placenta percreta with bladder invasion. After extracting the clots from the bladder, and coagulation of an area of venous ectasies of the posterior wall, hematuria ceased, but appeared after two days, necessitating again the bladder clots removal and coagulation. A surgical team with gynecologists, urologists, anesthesiologists and a neonatologist was composed, and after bilateral ureteral double J insertion, cesarean section was performed followed by hemostatic hysterectomy and partial cystectomy, bilateral internal iliac artery ligature and repair of the bladder wall. The postoperative evolution was without incidents; the Foley catheter was removed in the 14th postoperative day. CONCLUSION: In the context of a massive hematuria of a pregnant woman, the urologist must always consider a diagnosis of complicated placenta percreta.

The added value of three-dimensional ultrasonography in uterine pathology.

The rapid development achieved over the last decades in volume rendering of ultrasound data, known as three-dimensional (3D) ultrasound technique, leads to new opportunities for refining the diagnosis in many gynaecologic conditions. The aim of the present study was to evaluate the advantages of 3D ultrasound over two-dimensional (2D) ultrasound in uterine pathology and to establish the optimal time point during the menstrual cycle to perform 3D ultrasound examination in order to achieve the maximum of useful information. A cross-sectional study on 200 patients who underwent gynaecologic 2D and 3D ultrasound examinations was performed. The addition of 3D examination to 2D ultrasound in uterine pathology provided the most useful information concerning: Congenital uterine anomalies, intrauterine devices (IUDs), adenomyosis, and submucous myomas. The findings showed that the 3D ultrasound scan is a useful tool in gynaecology, especially in cases with congenital uterine anomalies, myoma, and IUD. Although initially it was used for research purposes only, recent findings suggest its usefulness in routine ultrasound scan and the possibility of witnessing its introduction as a recommended examination procedure in the foreseeable future. Further research should be conducted in order to establish the sensitivity of 3D ultrasound in the detection of minor endometrial conditions, by correlating the imaging findings with the hysteroscopic results.

Large ovarian tumors in adolescents, a systematic review of reported cases, diagnostic findings and surgical management.

The purpose of this study was to analyze the published cases regarding large ovarian masses in adolescents, in order to find useful clinical implications for the diagnosis and management of the condition. The methodology employed a systematic review of reported cases of large/giant ovarian tumor in adolescence. The main objective was to assess the imagery findings, histology of the tumor, and the type of surgery performed. Our study included 58 patients with the tumor diameters ranged between 11 and 42 cm, with a median value of 22.75 cm and a mean diameter of 24.66 ± 8.50 cm. The lesions were benign in 47 cases (81%), borderline in 2 cases (3.4%), and malign in 9 cases (15.6%). We found no statistically significant difference (p > 0.05) between the size of the tumors and the ovarian markers levels. At the same time, a statistically significant difference was identified (p=<0,001) between elevated levels of the serum markers and the malignant tumor type (OR = 12.45; CI95 = 2.55-94.77). The main types of surgery performed were cystectomy (35 cases), oophorectomy (4 cases), salpingo-oophorectomy (18 cases). Open laparotomy was performed in 46 cases on tumors with a median diameter of 25 ± 8.8 cm, while laparoscopy was done in 12 cases on tumors with a median diameter of 23.7 ± 7.6 cm. For optimal surgical management, it is advisable to assess first the imagery findings and tumor markers. Then, the laparoscopic approach should be considered as a feasible option, especially in cases where there are no predictive factors for a malign disease.

Transradial Embolization, an Underused Type of Uterine Artery Embolization Approach: A Systematic Review.

Background and Objectives: The most utilized approach for the embolization of uterine arteries is the transfemoral path. However, the transradial approach (TRA) has been gaining popularity among cardiologic interventions in the last years but only few studies have shown its applicability in uterine myoma treatment. The objective of this paper is to assess the feasibility, safety and efficacy of TRA when compared with the transbrachial, transulnar or transfemoral approach (TFA) for uterine arteries embolization (UAE). Materials and methods: A systematic review of the literature that analyzes the TRA for UAE it was carried out, in order to assess its safety and effectiveness. It was systematically searched the literature (Google Scholar, PubMed/MEDLINE, Cochrane Library and Embase) using the words ''uterine artery embolization''/''uterine embolization'' and ''transradial''/''radial''. All the relevant papers published until March 2020 were retrieved and analyzed. Results: Ten studies were considered eligible for this topic. TRA is a comparable method with TFA for uterine artery embolization. Conclusions: These studies allowed us to conclude that TRA is as safe and efficient as TFA. Its advantages include few complications, shorter hospitalization period, and rapid mobilization but a steeper learning curve has the disadvantage of a longer learning curve compared to TFA. Yet, these findings are built on few reports and more research is needed.

Logistic models and artificial intelligence in the sonographic assessment of adnexal masses - a systematic review of the literature.

Adnexal masses are common, yet challenging, in gynecological practice. Making the differential diagnosis between their benign and malignant condition is essential for optimal surgical management, but reliable pre-surgical differentiation is sometimes difficult using clinical features, ultrasound examination, or tumor markers alone. A possible way to improve the diagnosis is using artificial intelligence (AI) or logistic models developed based on compiling and processing clinical, ultrasound, and tumor marker data together. Ample research has already been conducted in this regard that medical practitioners could benefit from. In this systematic review, we present logistic models and methods using AI, chosen based on their demonstrated high performance in clinical practice. Although some external validation of these models has been performed, further prospective studies are needed in order to select the best model or to create a new, more efficient, one for the pre-surgical evaluation of ovarian masses.

Rare retroperitoneal conditions that mimic uterine myoma.

The most frequent tumoral condition of the uterus is represented by uterine myoma. The diagnosis, in most cases, is established by clinical examination and ultrasound scan. Nevertheless, there are rare cases, in which the surgical findings reveal a retroperitoneal tumor instead of a uterine myoma. These could be represented by schwannomas or Castleman disease. The schwannomas are rarely malignant and arise from the Schwann cells of nerve fibers. These tumors are frequently found at the level of the head, neck and mediastinum and rarely in the pelvis. Generally, schwannomas localized at retroperitoneal level are asymptomatic and with a very slow growth rate. The treatment consists in complete surgical resection. The recurrence rate is low and, generally, the prognosis is good. The Castleman disease is considered a rare entity, but it should be always taken into consideration when it comes to a differential diagnosis in a young patient who presents a retroperitoneal mass at imagery exams. The condition affects the lymphatic system and is characterized by a hyperplasia of the lymph nodes, sometimes associated with herpes virus infection. The clinical picture is often non-specific; the pain may be the only symptom. The imaging methods are not always conclusive for the final positive diagnosis and the histopathological examination is always necessary. Pelvic Castleman disease can be misdiagnosed as myoma or an adnexal tumor. In this article, we review the present knowledge regarding the pathogenesis, pathology and management of these rare retroperitoneal tumors. Both conditions, when located in pelvis must be taken into consideration in the differential diagnosis of uterine myomas, especially in the pedunculated form.

Abdominal wall endometriosis versus desmoid tumor - a challenging differential diagnosis.

AIM: Abdominal wall endometriosis (AWE) in young women, with previous gynecological abdominal surgery, is the first condition considered by many practitioners when a tumor in the region of the scar appears. AWE seems to be caused by an iatrogenic transfer of endometrial cells at the level of the scar. The onset of the disease may be late in many cases. Despite the fact that the disease could be totally asymptomatic, there are certain risk factors that can be identified during the anamnesis, such as: heredity, menarche at the age of >14 years, menstrual cycle <27 days, delayed menopause, excessive alcohol and caffeine consumption. Suggestive signs include cyclic or continuous abdominal pain caused by a palpable abdominal wall mass with a maximum tenderness in the region of the surgical scar. The differential diagnosis is complex and rare entities like desmoid tumors (DTs) must be taken into consideration. Desmoid tumor, or the so-called aggressive fibromatosis (AF), is a rare fibroblastic proliferation. This tumor can develop in any muscular aponeurotic structure of the body and is considered benign but with a high recurrence rate. DTs can cause local infiltration, subsequently producing certain levels of deformity and potential obstruction of vital structures and organs. The differential diagnosis is challenging in this situations, the imagery exams are useful, especially in detecting the precise location of the tumor. The histological examination of the tumor can state the final and precise diagnosis.

Morphological and histopathological changes in placentas of pregnancies with intrauterine growth restriction.

AIM: The definition of fetal growth restriction (FGR) refers to the incapability of a fetus to achieve the appropriate estimated growth, with expected fetal weight below the 10th percentile calculated for its gestational age. Placental factors and hypoxemia are considered to be essential elements with influence on intrauterine growth restriction (IUGR) and fetal death. The purpose of the present study was to investigate the macroscopic and microscopic pathological findings regarding the placentas in pregnancies complicated by influence on IUGR. PATIENTS, MATERIALS AND METHODS: Our study included 42 third-trimester pregnant patients admitted to the Cuza Voda Hospital of Obstetrics and Gynecology, Iasi, Romania, in the last three years. Soon after delivery, the 42 placentas were collected and analyzed; 32 placentas came from cases previously diagnosed with influence on IUGR and were included in our study group. Ten other placentas included in the control group were selected from uncomplicated pregnancies. Standard Hematoxylin-Eosin (HE) staining method, as well as Periodic Acid-Schiff (PAS) staining, and immunohistochemical techniques for cluster of differentiation 31 (CD31) and collagen IV were used in order to highlight the morphological features of the studied placentas. RESULTS: Our study revealed that reduced placental dimensions and eccentric umbilical cord insertion are correlated with the birthweight of the fetuses with IUGR (p<0.05). The most common histological finding in our study group was placental infarction later correlated with IUGR, but a certain causality could not be demonstrated, as this finding was also present in normal pregnancies. Other histopathological findings were also present in the influence on IUGR group, such as fibrin deposits, diffuse calcification, chronic villitis, avascular chronical villi, with no significant statistical correlations. CD31 was strongly immunoexpressed in the villous endothelial cells. Collagen IV presented a strong immunoreaction in the basement membrane and mesenchyme of the placental villi. CONCLUSIONS: Our study revealed a correlation between the dimensions of the diameters and volume of the maternal placenta and the presence of influence on IUGR. Moreover, it confirms the available data suggesting that the place of insertion of the umbilical cord is correlated with the weight of the fetus. Further studies with extended panel antibodies are needed in order to determine and complete the role of these morphological changes in the development of influence on IUGR.

Early prenatal diagnosis of a lumbo-costo-vertebral syndrome.

Lumbo-costo-vertebral syndrome (LCVS) is a rare type of lumbar hernia with associated abnormalities of the vertebral bodies, ribs, and trunk muscles. Only a few cases have been reported in the literature, all of which were diagnosed after birth. We present a case of LCVS diagnosed early in the second trimester of pregnancy using two- and three-dimensional ultrasound. In our case, the associated anomalies were: multiple costovertebral anomalies, lumbar hernia, anal imperforation, left hand supernumerary digit, and clubfoot.

Three-dimensional ultrasound and HDlive in tubal serous cystadenofibroma: a case report and literature review.

Cystadenofibromas of the fallopian tubes are very rare benign tumors and very few cases have been reported in the literature worldwide. Usually, the tumor is asymptomatic, and for almost all cases reported, the tumors were incidentally discovered during surgery for other genital pathology. We report the case of a 30-year-old woman with a serous cystadenofibroma of the fallopian tube, presenting with chronic abdominal pain and secondary infertility. The diagnosis of tubal tumor was formulated before surgery and confirmed during laparoscopic surgery. Both 3D ultrasound and HDlive were useful tools for the diagnosis. The ultrasound diagnosis was helpful in planning appropriate surgical management.

Perception and use of Pap smear screening among rural and urban women in Romania.

Background: In 2012 the National Screening Program for all women between 25 and 64 years of age was launched in Romania. Public awareness is an important factor in the success of a screening program. For this reason, we intended to assess the perception and the level of awareness of Romanian women regarding the Pap test in the prevention of cervical cancer. Methods: A cross-sectional study was conducted among 454 women from rural and urban areas. For our study, we used a questionnaire covering general characteristics, awareness, knowledge and practices regarding cervical cancer and Pap smear. Results: 431 participants (95%) had heard of cervical cancer and Pap smear but only 71.8% knew the exact role of it. Bivariate analysis showed that knowledge about the importance of the Pap smear, early detection and treatment of early-stage cervical cancer was reduced among women with low socio-economic status, mainly living in rural area. The most frequent reasons for avoiding Pap smear screening were: lack of money, embarrassment or fear of gynaecological consultation and pain, the feeling that they don't need it, misconceptions about cervical cancer, fatalistic attitude, perceived low susceptibility to cervical cancer. Conclusions: Because the uptake and the success of cervical cancer screening are determined by women's knowledge and awareness of Pap smear, it is critical to improve these perceptions in the near future especially in rural area characterized by a low socio-economic status.

Three dimensional ultrasound and hdlive technology as possible tools in teaching embryology.

Embryology is an important subject in order to gain an understanding of medicine and surgery; however, sometimes students find the subject difficult to grasp and apply to clinical practice. Modern imaging techniques can be useful aids in teaching and understanding embryology. Imaging techniques have very rapidly evolved over the last few years, advancing from two- to three-dimensional (3D) ultrasound. HDlive is an innovative ultrasound technique that generates near-realistic images of the human fetus. In order to evince the capabilities of 3D ultrasound and HDlive technology in teaching embryology, we evaluated using this technique the normal evolution of the embryo and fetus from the fifth to eleventh week of amenorrhea. Our conclusion is that by yielding clear and impressive images, 3D ultrasound and HDlive could be useful tools in teaching embryology to medical students. Clin. Anat. 30:953-957, 2017. © 2017 Wiley Periodicals, Inc.

The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways.

MOTIVATION: Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions. RESULTS: The Biological Connection Markup Language (BCML) is a format to describe, annotate and visualize pathways. BCML is able to store multiple information, permitting a selective view of the pathway as it exists and/or behave in specific organisms, tissues and cells. Furthermore, BCML can be automatically converted into data formats suitable for analysis and into a fully SBGN-compliant graphical representation, making it an important tool that can be used by both computational biologists and 'wet lab' scientists. AVAILABILITY AND IMPLEMENTATION: The XML schema and the BCML software suite are freely available under the LGPL for download at http://bcml.dc-atlas.net. They are implemented in Java and supported on MS Windows, Linux and OS X.

DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells.

BACKGROUND: The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs). RESULTS: Pathways are annotated using a novel data model, the Biological Connection Markup Language (BCML), a SBGN-compliant data format developed to store the large amount of information collected. The application of DC-ATLAS to pathway-based analysis of the transcriptional program of DCs stimulated with agonists of the toll-like receptor family allows an integrated description of the flow of information from the cellular sensors to the functional outcome, capturing the temporal series of activation events by grouping sets of reactions that occur at different time points in well-defined functional modules. CONCLUSIONS: The initiative significantly improves our understanding of DC biology and regulatory networks. Developing a systems biology approach for immune system holds the promise of translating knowledge on the immune system into more successful immunotherapy strategies.