Tertiary prevention strategies for micrometastatic lymph node cervical cancer: A systematic review and a prototype of an adapted model of care.

PURPOSE: We found a need for balancing the application of clinical guidelines and tailored approaches to follow-up of cervical cancer (CC) patients in the lymph node micrometastatic (MICs) setting. This review aimed to determine the current knowledge of management of MIC-positive CC cases. METHODOLOGY: We addressed prognostic and risk of recurrence monitoring impacts associated with MIC+ cases. The electronic databases for literature and relevant articles were analysed. RESULTS: Fifteen studies, (4882 patients), were included in our systematic review. While the results show that MICs significantly worsen prognosis in early CC. A tertiary prevention algorithm for low volume lymph node disease may stratify follow-up according to the burden of nodal disease and provide data that helps improve follow-up performance. CONCLUSION: MICs worsen prognosis and should be managed as suggested by the algorithm. However, this algorithm must be externally validated. The clinical impact of isolated tumor cells (ITC) remains unclear.

Intrauterine deaths - an unsolved problem in Polish perinatology.

OBJECTIVES: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. MATERIAL AND METHODS: An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. RESULTS: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. CONCLUSIONS: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer.

Selenium (Se) and manganese (Mn) are essential micronutrients that are important elements of cell metabolism. They are involved in the composition of enzyme systems and regulate enzyme activity. Disturbances in the homeostasis of these micronutrients affect the development of many diseases and carcinogenesis, which can be linked to increased levels of oxidative stress and impaired antioxidant properties of many enzymes. Selenium has a very important function in maintaining immune-endocrine, metabolic and cellular homeostasis. Manganese, on the other hand, is important in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activity. We review the role of selenium and manganese and their effects on tumor growth, metastasis potential and remodeling of the microenvironment. We also describe their role as potential biomarkers in the diagnosis and the potential for the use of Se- and Mn-containing compounds in composition for the treatment of cancer of the reproductive organs.

Influence of Vitamin D on the Incidence of Metabolic Syndrome and Hormonal Balance in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that affects 8-13% of women of reproductive age. It is one of the most common causes of infertility and is associated with hyperandrogenism in the form of hirsutism and acne, non-ovulatory cycles, and characteristic ovarian morphology. The available research on serum vitamin D deficiency in patients with PCOS and the appropriateness of vitamin D supplementation in this group of women is inconclusive, so we decided to investigate the influence of vitamin D on the incidence of metabolic syndrome and hormonal balance in patients with polycystic ovary syndrome. The study comprised 120 women aged between 18 and 42 years, who were divided into two groups: a group with diagnosed polycystic ovary syndrome (PCOS) and a group of regularly menstruating women without features of androgenisation, in whom polycystic ovary syndrome was excluded. Each patient underwent a history and physical examination, including a gynecological examination, anthropometric measurements were taken, including height, weight, waist, and hip circumference, and blood pressure was measured using the Korotkow method. In the female patients, the following parameters were also determined from the blood: follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, TSH, ft4, prolactin (PRL), total testosterone, DHEASO4, 17-hydroxyprogesterone (17-OHP), sex-hormone-binding globulin (SHBG), androstendione, 25(OH) vitamin D3 metabolite. The majority of the patients with polycystic ovary syndrome were found to have deficient or suboptimal serum vitamin D levels, and the effects of vitamin D on the SHBG levels and free-androgen indices in these patients was examined. The effects of vitamin D on the incidence of metabolic syndrome and BMI, waist-to-hip ratio, waist circumference, and blood pressure in patients with polycystic ovary syndrome were also found.

Performance of IOTA Simple Rules Risks, ADNEX Model, Subjective Assessment Compared to CA125 and HE4 with ROMA Algorithm in Discriminating between Benign, Borderline and Stage I Malignant Adnexal Lesions.

BACKGROUND: Borderline ovarian tumors (BOTs) and early clinical stage malignant adnexal masses can make sonographic diagnosis challenging, while the clinical utility of tumor markers, e.g., CA125 and HE4, or the ROMA algorithm, remains controversial in such cases. OBJECTIVE: To compare the IOTA group Simple Rules Risk (SRR), the ADNEX model and the subjective assessment (SA) with serum CA125, HE4 and the ROMA algorithm in the preoperative discrimination between benign tumors, BOTs and stage I malignant ovarian lesions (MOLs). METHODS: A multicenter retrospective study was conducted with lesions classified prospectively using subjective assessment and tumor markers with the ROMA. The SRR assessment and ADNEX risk estimation were applied retrospectively. The sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) were calculated for all tests. RESULTS: In total, 108 patients (the median age: 48 yrs, 44 postmenopausal) with 62 (79.6%) benign masses, 26 (24.1%) BOTs and 20 (18.5%) stage I MOLs were included. When comparing benign masses with combined BOTs and stage I MOLs, SA correctly identified 76% of benign masses, 69% of BOTs and 80% of stage I MOLs. Significant differences were found for the presence and size of the largest solid component (p = 0.0006), the number of papillary projections (p = 0.01), papillation contour (p = 0.008) and IOTA color score (p = 0.0009). The SRR and ADNEX models were characterized by the highest sensitivity (80% and 70%, respectively), whereas the highest specificity was found for SA (94%). The corresponding likelihood ratios were as follows: LR+ = 3.59 and LR- = 0.43 for the ADNEX; LR+ = 6.40 and LR- = 0.63 for SA and LR+ = 1.85 with LR- = 0.35 for the SRR. The sensitivity and specificity of the ROMA test were 50% and 85%, respectively, with LR+ = 3.44 and LR- = 0.58. Of all the tests, the ADNEX model had the highest diagnostic accuracy of 76%. CONCLUSIONS: This study demonstrates the limited value of diagnostics based on CA125 and HE4 serum tumor markers and the ROMA algorithm as independent modalities for the detection of BOTs and early stage adnexal malignant tumors in women. SA and IOTA methods based on ultrasound examination may present superior value over tumor marker assessment.

Protocol of Breast Cancer Prevention Model with Addition of Breast Ultrasound to Routine Gynecological Visits as a Chance for an Early Diagnosis and Treatment in 25 to 49-Year-Old Polish Females.

The low attendance rate for cancer screening tests in Poland is a major healthcare concern that requires specific analysis and the development of implementation recommendations for prevention, and both actions are likely to benefit culturally similar countries. Four female cancers account for approximately 20% of all cancer cases-breast cancer, cervical cancer, endometrial cancer, and ovarian cancer-suggesting that gynecologists have a significant preventative role. Of the four, breast cancer and cervical cancer are among the 10 most common malignant neoplasms globally, regardless of gender, occur only in women and are known to have effective screening measures. Our research aims to create a screening model that combines cervical cancer and breast cancer to maximize health outcomes for women at risk of both cancers. In the study protocol, we have created a model that maximizes benefits for patients with minimal additional costs to the health care system. To achieve the set goal, instead of regular clinical breast exams as recommended by the gynecological societies, we proposed an ultrasound examination, during which palpation may also be performed (in the absence of elastography). We present a scheme for such a protocol that takes into consideration all types of prevention in both cancers, and that emphasizes breast ultrasound as the most frequently missing element. Our study includes a discussion of the strengths and weaknesses of our strategy, and the crucial need for infrastructure and education for the successful implementation of the program. We conclude that our model merits consideration and discussion among health-care decision makers, as the screening changes we propose have significant potential benefits for the female population.

Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications.

Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is in progress. The aim of the study was to assess the dominant energy substrate transport mechanism in ovarian cancer cells and to verify whether genomic aberrations could predict clinical outcomes using the Cancer Genome Atlas (TCGA) dataset. Total RNA was extracted from HGSC frozen tissues, and the expression of selected genes was compared to respective controls. GLUT1, FABPpm, MCT4 and SNAT1 genes were significantly overexpressed in carcinomas compared with controls, while expression of CD36/SR-B2, FATP1, FABP4, GLUT4, ASCT2 and LPL was decreased. No differences were found in FATP4, LAT1, MCT1 and FASN. The transcript content of mitochondrial genes such as PGC-1α, TFAM and COX4/1 was similar between groups, while the ß-HAD level declined in ovarian cancer. Additionally, the MCT4 level was reduced and PGC-1α was elevated in cancer tissue from patients with 'small' primary tumor and omental invasion accompanied by ascites as compared to patients that exhibited greater tendencies to metastasize to lymph nodes with clear omentum. Based on TCGA, higher FABP4 and LPL and lower TFAM expression indicated poorer overall survival in patients with ovarian cancer. In conclusion, the presented data show that there is no exclusive energy substrate in HGSC. However, this study indicates the advantage of glucose and lactate transport over fatty acids, thereby suggesting potential therapeutic intervention targets to impede ovarian cancer growth.

Thousands of Women's Lives Depend on the Improvement of Poland's Cervical Cancer Screening and Prevention Education as Well as Better Networking Strategies Amongst Cervical Cancer Facilities.

Proper targeted cancer prophylaxis reduces the incidence of cancer in all forms; this includes cancers with significant progression potential and poor prognosis. Based on the assumption that one of the risk factors of cervical cancer is the avoidance of screening tests, we analyzed the current scenario of cervical cancer (CC) screening and recommendations in Poland (country with a well-off socioeconomic status). Based on the comprehensive literature review concerning documents of guidelines and recommendations of various bodies, including national ones, data on the implementation of CC screening in Poland, and different models for medium-to-high-income countries, we proposed how the CC screening strategy could be improved. Finally, the new strategy was further developed for those who are prone to not being screened. The proposal on how to improve the Polish CC screening program is the following: refinement of the public education on CC risk factors, popularization of CC screening incentives amongst the public, and improvement of networking strategies between CC screening facilities ("cervical screening clinical"), allowing screenings to be more efficient and rapid. We believe that, to enhance the future quality of life of those with rapid CC progression by catching the disease preemptively and limiting the sequelae of the disease, we have to improve education and access to medical services.

Uterine Myomas and Sarcomas - Clinical and Ultrasound Characteristics and Differential Diagnosis Using Pulsed and Color Doppler Techniques.

Uterine tumors are a challenge encountered by every gynecologist in clinical practice. In the era of increasing incidence of endometrial cancer in the general population of women at reproductive age, compared to other genital malignancies, we should not forget about other tumors originating from the mucous and muscular layer of the uterus. Clear ultrasonographic differentiation of uterine tumors into benign (myomas) and malignant (sarcomas) lesions may sometimes prove impossible. Myomas, the most common uterine tumors, are characterized by discrete vascularization on color Doppler and high blood flow velocity as well as the lack of early diastolic notch on Doppler ultrasound. Sarcomas, on the other hand, show characteristic rich vascularization. Rapid tumor growth should also be noted when making the diagnosis. There are multiple known causes of uterine tumors. So far, no clear Doppler flow markers have been identified to characterize benign and malignant lesions.

Immunohistochemical Subtypes of The Breast Cancer in The Ultrasound and Clinical Aspect - Literature Review.

Breast cancer is a heterogeneous disease both in its clinical and radiological manifestations and response to treatment. This is largely due to the polymorphism of the histological types as well as diversified molecular profiles of individual breast cancer types. Progress in the understanding of the biology of breast cancer was made with the introduction of immunohistochemical research into the common practice. On this basis, four main breast cancer subtypes were distinguished: luminal A, luminal B, HER2 positive (human epidermal growth factor receptor-2 positive), and triple negative cancer. The classification of a tumour to an appropriate subtype allows for the optimisation of treatment (surgery or pre-operative chemotherapy). In this study, the authors present different patterns of breast cancer subtypes in ultrasound examination and differences in their treatment, with particular emphasis on aggressive breast cancer subtypes, such as triple negative or HER2 positive. They can, unlike the luminal subtypes, create diagnostic problems. Based on multifactorial analysis of the ultrasound image, with the assessment of lesion margins, orientation, shape, echogenicity, vascularity, the presence of calcifications or assessment by sonoelastography, it is possible to initially differentiate individual subtypes.

Increased Risk of COVID-19 in Patients with Diabetes Mellitus-Current Challenges in Pathophysiology, Treatment and Prevention.

Coronavirus disease-COVID-19 (coronavirus disease 2019) has become the cause of the global pandemic in the last three years. Its etiological factor is SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus type 2). Patients with diabetes (DM-diabetes mellitus), in contrast to healthy people not suffering from chronic diseases, are characterised by higher morbidity and mortality due to COVID-19. Patients who test positive for SARCoV-2 are at higher risk of developing hyperglycaemia. In this paper, we present, analyse and summarize the data on possible mechanisms underlying the increased susceptibility and mortality of patients with diabetes mellitus in the case of SARS-CoV-2 infection. However, further research is required to determine the optimal therapeutic management of patients with diabetes and COVID-19.

Implementation of the Publicly Funded Prenatal Screening Programme in Poland during the COVID-19 Pandemic: A Cross-Sectional Study.

The COVID-19 pandemic in 2020 affected the entire healthcare system in Poland, causing medical personnel to be relocated to other duties and limiting patients' contacts with healthcare professionals. A large part of the planned diagnostics and treatment was delayed due to lack of equipment and personnel. Against this background, we analysed the implementation of the publicly funded prenatal screening programme (PSP) in Poland compared to the previous year. This is a cross-sectional study. We used nationwide datasets on the implementation of the prenatal testing programme over the period 2019−2020, datasets from the Statistics Poland on birth and the data on the development of the COVID-19 epidemic in Poland. In the year 2020, we observed a 12.41% decrease in woman enrolled to the programme compared to 2019. However, the decrease concerned only women under 35 years of age. With respect to the number of deliveries in the calendar year, the number of patients enrolled in the programme decreased by 3% (31% vs. 34%, p < 0.001). We also observed an increase in estriol measurements per the number of patients included in the programme, and a reduction in the number of PAPP-A tests in the first trimester, which proves an increased share of the triple test in the prenatal diagnosis of chromosomal aberrations. With respect to the number of deliveries, the number of amniocentesis procedures performed under PSP decreased by 0.19% (1.8% vs. 1.99%, p < 0.0001). In 2020, compared to the previous year, the number of patients included in the prenatal testing programme in Poland decreased. In terms of the number of births in Poland, the number of integrated screening tests also decreased, at the expense of increasing the percentage of triple tests. There were also significant reductions in the number of invasive diagnostic tests.

Obesity and Energy Substrate Transporters in Ovarian Cancer-Review.

Ovarian cancer is the seventh most common cancer in women. It is characterized by a high mortality rate because of its aggressiveness and advanced stage at the time of diagnosis. It is a nonhomogenous group of neoplasms and, of which the molecular basics are still being investigated. Nowadays, the golden standard in the treatment is debulking cytoreductive surgery combined with platinum-based chemotherapy. We have presented the interactions and the resulting perspectives between fatty acid transporters, glucose transporters and ovarian cancer cells. Studies have shown the association between a lipid-rich environment and cancer progression, which suggests the use of correspondent transporter inhibitors as promising chemotherapeutic agents. This review summarizes preclinical and clinical studies highlighting the role of fatty acid transport proteins and glucose transporters in development, growth, metastasizing and its potential use in targeted therapies of ovarian cancer.

Two Concurrent Cancers in a 19-Year-Old Patient: Yolk Sac Ovarian Tumor and Metastatic Gastrointestinal Tract Malignancy-Case Report.

BACKGROUND: Two concurrent malignancies present in a young person is an extremely rare condition. Diagnoses of gastric cancer primarily concern older patients. There are very few reports of concomitant Krukenberg tumor and germ-cell ovarian malignancy. CASE: A 19-year-old girl was admitted to the gynecologic oncology department with symptoms of advanced malignancy. Radiological imaging revealed disseminated neoplastic disease with bulky adnexal tumors. Cytoreductive surgery was performed, achieving no visible disease (T = 0 cm). The final pathology report confirmed metastatic mixed adenoneuroendocrine carcinoma (MANEC) in both ovaries, originating from the gastrointestinal tract. Moreover, the primary germ cell yolk sac tumor was found in the left ovary. CONCLUSION: In cases of concomitant gastric and ovarian tumors, metastatic disease (Krukenberg tumor) should be considered in the differential diagnosis. This concerns even adolescent patients. In particular cases, including tumors with germ cell components, primary debulking surgery is crucial for prognosis.

Diabetic Mastopathy. Review of Diagnostic Methods and Therapeutic Options.

Diabetic mastopathy is a rare breast condition that may occur in insulin-treated men and women of any age. The etiology is still unclear; however, the autoimmunological background of the disease is highly suspected. The changes in diabetic mastopathy may mimic breast cancer; therefore, its diagnostic process is demanding, and treatment options are not clear and limited. Lesions in DM are usually multiple; therefore, surgical removal is not fully effective. A well-done anamnesis with core-needle biopsy is essential and definitive in most cases. In this review, we summarize up-to-date knowledge of diagnostic methods and therapeutic options for diabetic mastopathy treatment and present three cases of diabetic mastopathy-type lesions in ultrasound and radiological examinations.

Synthesis of amide and sulfonamide substituted N-aryl 6-aminoquinoxalines as PFKFB3 inhibitors with improved physicochemical properties.

In oncology, the "Warburg effect" describes the elevated production of energy by glycolysis in cancer cells. The ubiquitous and hypoxia-induced 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) plays a noteworthy role in the regulation of glycolysis by producing fructose-2,6-biphosphate (F-2,6-BP), a potent activator of the glycolysis rate-limiting phosphofructokinase PFK-1. Series of amides and sulfonamides derivatives based on a N-aryl 6-aminoquinoxaline scaffold were synthesized and tested for their inhibition of PFKFB3 in vitro in a biochemical assay as well as in HCT116 cells. The carboxamide series displayed satisfactory kinetic solubility and metabolic stability, and within this class, potent lead compounds with low nanomolar activity have been identified with a suitable profile for further in vivo evaluation.

Discovery and Structure-Activity Relationships of N-Aryl 6-Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors.

Energy and biomass production in cancer cells are largely supported by aerobic glycolysis in what is called the Warburg effect. The process is regulated by key enzymes, among which phosphofructokinase PFK-2 plays a significant role by producing fructose-2,6-biphosphate; the most potent activator of the glycolysis rate-limiting step performed by phosphofructokinase PFK-1. Herein, the synthesis, biological evaluation and structure-activity relationship of novel inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which is the ubiquitous and hypoxia-induced isoform of PFK-2, are reported. X-ray crystallography and docking were instrumental in the design and optimisation of a series of N-aryl 6-aminoquinoxalines. The most potent representative, N-(4-methanesulfonylpyridin-3-yl)-8-(3-methyl-1-benzothiophen-5-yl)quinoxalin-6-amine, displayed an IC50 of 14 nm for the target and an IC50 of 0.49 µm for fructose-2,6-biphosphate production in human colon carcinoma HCT116 cells. This work provides a new entry in the field of PFKFB3 inhibitors with potential for development in oncology.