Uterine Leiomyomas with Specific Histology Features of Two Fumarate Hydratase/Succinate Dehydrogenase-Deficient Tumors: A Double Case Report.

Background and Objectives: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of certain types of histomorphologically specific leiomyomas that hold significant predictive value. Materials and Methods: This study presents two cases of uterine leiomyomas exhibiting rare histomorphological and genetic characteristics, which are crucial for prognosis and further treatment. Results: Distinct histopathological features such as marked nuclear atypia, intracellular eosinophilic globules, and abnormal intratumoral vessels raise suspicion for specific leiomyoma subtypes, which carry predictive significance for additional hereditary cancer syndromes. Immunohistochemical analysis confirmed FH/SDH deficiency in both patients, who underwent careful follow-up. Conclusions: This study describes two cases involving unusual leiomyomas, the histopathological characteristics of which may easily go unrecognized. These features hold predictive significance because their specific mutations point to additional hereditary cancer syndromes, highlighting the need for further examinations.

Curious Case of Superfitial Spreading Cervical Squamocellular Carcinoma with Adnexal Involvement.

Background and Objectives: Cervical squamous cell carcinoma (SCC) usually showed an infiltrative growth pattern into endocervical stroma. In rare cases, SCC spreads superficially as an intraepithelial lesion to proximal uterine segments, and more rarely, involves invasive and more aggressive behavior on secondary sites. Materials and Methods: In this study, we present the case of an interesting form of cervical SCC growth and we discuss the possible reasons for that presentation. Results: After clinical examination and repeated histomorphological analysis, we found remarkable cervical epithelial dysplasia (a high-grade squamous intraepithelial lesion-H-SIL). A histopathology report after conization and hysterectomy showed squamocellular carcinoma with microinvasive focuses. Interestingly, squamocellular carcinoma was found in the proximal uterine and adnexal structure, as well as intraepithelial and microinvasive lesions. Conclusions: Our study described a rare presentation of primary cervical SCC with unusual adnexal involvement. This pattern of tumor growth should be especially considered for patients who are proposed for sparing surgical procedures. A detailed and multidisciplinary approach for every patient is very important because unpredictable cases are present. However, they are rare.

Neonatal Pneumothorax Outcome in Preterm and Term Newborns.

Background and Objectives: Pneumothorax implies the presence of air in the pleural space between the visceral and parietal pleura. The aim of this study was to investigate the incidence, clinical characteristics, risk factors, therapy and perinatal outcome in neonates with pneumothorax in a tertiary care center. Materials and Methods: A retrospective study based on a five-year data sample of neonates with pneumothorax was conducted in a Maternity Hospital with a tertiary NICU from 2015 to 2020. We included all neonates with pneumothorax born in our hospital and compared demographic characteristics, perinatal risk factors, anthropometric parameters, comorbidities, clinical course and method of chest drainage between term (≥37 GW) and preterm (<37 GW) neonates. Results: The study included 74 newborns with pneumothorax, of which 67.6% were male and 32.5% were female. The majority of women (59.5%) had no complications during pregnancy. Delivery was mainly performed via CS (68.9%). Delivery occurred on average in 34.62 ± 4.03 GW. Significantly more (p = 0.001) children with pneumothorax were born prematurely (n = 53; 71.6%) than at term (n = 21; 28.4%). Most of the neonates had to be treated with ATD (63.5%) and nCPAP (39.2%), but less often they were treated with surfactant (40.5%) and corticosteroids (35.1%). O2 therapy lasted an average of 8.89 ± 4.57 days. Significantly more (p = 0.001) neonates with pneumothorax had additional complications, pneumonia, sepsis, convulsions and intraventricular hemorrhage (68.9%). However, most children had a good outcome (83.8%) and were discharged from the clinic. Fatal outcomes occurred in six cases, while another six neonates had to be transferred to referral neonatal centers for further treatment and care. Conclusion: Significantly more children with pneumothorax were born prematurely than at term. With adequate therapy, even premature newborns can successfully recover from pneumothorax.

Importance of Staphylococcus epidermidis findings in the blood and cerebrospinal fluid of a full-term newborn: a case report.

Methicillin-resistant Staphylococcus epidermidis (MRS) predominantly colonizes the skin and mucous membranes of humans and other animals. We describe the case of a male newborn of gestational age 39 weeks whose primary and repeated blood cultures and cerebrospinal fluid samples isolated MRS. The choice and duration of antibiotic therapy were determined by the clinical presentation, infection parameters, and results of bacteriological analyses of blood and cerebrospinal fluid samples obtained from the newborn on the day 5 of life. After 28 days of antibiotic therapy for sepsis accompanied by meningitis, the newborn was discharged home without sequelae.

The Effect of Glucose Metabolism and Breastfeeding on the Intestinal Microbiota of Newborns of Women with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a pregnancy complication in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. The diet and lifestyle of the mother during pregnancy as well as lactation have long-term effects on the child's health and development. Detection of early risk markers of adult-age chronic diseases that begin during prenatal life and the application of complex nutritional interventions at the right time may reduce the risk of these diseases. Newborns adapt to the ectopic environment by developing intestinal immune homeostasis. Adequate initial colonization of bacteria is necessary for sufficient development of intestinal immunity. The environmental determinant of adequate colonization is breast milk. Although a developing newborn is capable of producing an immune response, the effector immune component requires bacterial stimulation. Breast milk stimulates the proliferation of a well-balanced and diverse microbiota, which initially influences the switch from an intrauterine TH2 predominant to a TH1/TH2 balanced response and the activation of T-regulatory cells by breast milk-stimulated specific organisms (Bifidobacteria, Lactobacillus, and Bacteroides). Breastfeeding in newborns of mothers with diabetes mellitus regulates the adequate immune response of the newborn and prevents diseases of the neonatal and postnatal period.

PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate.

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

Neurological impairments in hypoxic neonates and lactate levels.

INTRODUCTION: Metabolic acidosis with increasing lactate concentration develops due to the lack of oxygen in the tissues. OBJECTIVES: The effect of lactic acidosis on neurological development in the first year of life. MATERIALS AND METHODS: Our study included 50 newborns with perinatal hypoxia requiring oxygen therapy and 50 healthy newborns. pH, pCO2, pO2, base excess (BE) and lactates from arterialized capillary blood were determined in both groups of newborns, in the first and second hours after birth, and neurological development in the first year of life was estimated. RESULTS: pH, pCO2, pO2, BE and lactates differed significantly between the groups in the first and second hours after birth p < 0.01. Hypotonia was recorded in 20/50 cases and hypertonia was recorded in 10/50 cases in the first year of life. CONCLUSION: Lactate concentration may be an indicator of neurological damage in neonates with perinatal hypoxia.

Lipids on the Second Day in Ischemic and Normoxemic Term Neonates.

INTRODUCTION: In hypoxic newborns requiring oxygen, lipid peroxidation affects the peripheral blood lipids. OBJECTIVES: Determine the influence of perinatal oxygen therapy for hypoxia on serum lipid concentrations on the second day of life. MATERIALS AND METHODS: Our study included 50 newborns with perinatal hypoxia requiring oxygen and 50 healthy newborns without oxygen therapy. Arterialized capillary blood was taken for categorization of hypoxia (pO2) after birth in both groups. Lipid concentrations: total cholesterol (TC), high density lipoproteins (HDL), low density lipoproteins (LDL), and triglycerides (TG) were measured on day 2 in both groups. RESULTS: TC, LDL, HDL, TG, HC03 levels were statistically lower in the study group compared to the control one, while pCO2 and BE levels were statistically higher in newborns with perinatal hypoxia. CONCLUSION: Lower lipid levels in hypoxic newborns may suggest that circulating lipids are oxidized, peroxidized, and removed from the peripheral circulation.

Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance.

BACKGROUND: Insulin resistance (IR) in adults has been associated with intrauterine growth restriction (IUGR). Leptin and adiponectin correlations with anthropometric parameters and IR at 72 h in discordant twins were tested. METHODS: We included 24 discordant (birth weight discordance ≥20% in relation to the heavier cotwin) and 30 concordant (birth weight discordance ≤10%) twins. RESULTS: A correlation between leptin (but not adiponectin) level and birth weight (BW), birth length and head circumference in IUGR twins was recorded (p<0.05). Insulin sensitivity (IS) and homeostatic model assessment (HOMA)-IR in IUGR twins were similar to appropriate-for-gestational-age cotwins and unrelated to adipokines. In IUGR twins, adiponectin and insulin associated positively. In larger concordant twins' leptin level correlated with HOMA-IR and insulin. CONCLUSIONS: Leptin, but not adiponectin, levels correlate positively with anthropometric parameters in IUGR twins. IR in IUGR twins is unrelated to adipokines in the first few days of life.

Lipids and Adipokines in Cord Blood and at 72 h in Discordant Dichorionic Twins.

BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for developing metabolic syndrome later in life. We explored whether adipokine concentrations in cord blood (CB) and on day 3 (D3) were related to impaired fetal growth and lipids in IUGR twins. PATIENTS AND METHODS: Thirty-six discordant (birth weight [BW] discordance ≥20% calculated in relation to the heavier co-twins) and 42 concordant (BW discordance ≤ 10%) twin pairs were included. RESULTS: In IUGR twins, both adiponectin/BW and triglyceride (TG) levels were significantly higher, while total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were lower in CB. On D3, both leptin and HDL-C levels were significantly lower and TG levels were significantly higher in IUGR twins. In the discordant group, the alterations in lipids were not related to any adipokine. CONCLUSIONS: IUGR is related to lower leptin level and proatherogenic lipid profile (higher TG and lower HDL-C), which are not influenced by adipokine at birth.

Risk of Parametrial Spread in Small Stage I Cervical Carcinoma: Pathology Review of 223 Cases With a Tumor Diameter of 20 mm or Less.

BACKGROUND: Considering the morbidity of radical hysterectomy, the advent of fertility-sparing approaches, and the low risk of parametrial involvement in patients with early stage I cervical tumors, the benefit from parametrial resection is debatable. Objectives of this study were to determine factors predicting parametrial tumor spread and to define a group of patients who might be safely spared parametrial resection. METHODS: Pathology review was done on patients with stages IA2 and small IB1, treated by radical hysterectomy and pelvic lymph node dissection. Analysis was performed to determine factors associated with parametrial spread and to define risks of obeying parametrial resection. RESULTS: A total of 223 patients with tumors less than 20 mm in diameter were identified. Parametrial metastases were documented in 8 patients (3.6%); nodes, 1.3%; lymphovascular space invasion (LVSI), 1.8%; contiguous spread, 0.9%. Of 211 (94.6%) patients with negative pelvic nodes, none had parametrial nodal involvement, 0.9% had LVSI, and 0.4% had contiguous spread. Factors associated with parametrial disease were deep cervical invasion, LVSI, tumor volume, and pelvic lymph node metastases (P < 0.01 for each). In patients without tumor LVSI and the depth of invasion was within the inner third, the rate of parametrial spread was 0.45%. CONCLUSIONS: Our data show a risk of parametrial spread of 0.45% for tumors less than 20 mm in diameter, no LVSI, and a depth of invasion within the inner third. Patients wanting fertility preservation might be prepared to take this risk of recurrence. Morbidity after nerve-sparing radical hysterectomy is tolerably low, and for patients in whom fertility preservation is not an issue, this should be considered the standard of care.

Reliability and relationship of colposcopical, cytological and histopathological findings in the diagnostic process.

BACKGROUND/AIM: The question about the accuracy of cytology and colposcopy is more and more asked due to false positive and negative findings on the basis of which the decision on biopsy is made. The aim of this study was to examine reliability of biopsies based only on abnormal colposcopical findings, before receiving the results of Papanicolaou (PA) smear, by comparing findings of colposcopical, cytological and histopathological (HP) examinations as well as determining validity of these diagnostic methods. METHODS: The study involved all patients who had their regular colposcopical and cytological examinations in the outpatient department during a two-year period (2009-2010) in the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade. The material for HP examination was obtained by colposcopically directed biopsy, due to abnormal colposcopical findings and without waiting for PA smear results. The data obtained by these methods were statistically analyzed and compared. Furthermore, validity of colposcopical and cytological examinations was assessed. Results. Out of 127 patients highly significantly more patients had more malignant cervical changes on colposcopical exam compared to HP (p = 0.000), and cytological exam (p = 0.000). Highly significantly more patients had more malignant cervical changes on PA smear than HP exam (p = 0.000), unless when findings were assessed in the widest sense of benign and malignant changes when there were no significant differences in these findings (p = 0.450). Sensitivity of colposcopy as a diagnostic method was 87.5%, specificity 24.14%, positive predictive value (+PV) was 34.65% and negative predictive value (-PV) 80.77%. Sensitivity of PA smear as a diagnostic method was 62.5%, specificity 87.36%, +PV was 69.44%, and -PV 83.52%. CONCLUSION: Regarding the results of our study it is best to make a decision on treatment according to findings of all the three methods. Cytological analysis is more reliable than colposcopical examination. Therefore, it is advisable that following abnormal colposcopical findings, PA smear should always be taken and only after receiving the results further diagnostics can be planned (biopsy and HP). A final decision on the therapy has to be made based on HP findings which are the only method that can give the ultimate reliable diagnosis of cervical changes.

Introduction of new Tumor Marker Age Score in clinical practice: Validity evaluation for differentiation benign from malignant adnexal masses.

OBJECTIVE: The aim of the study was to examine several tumor markers and their correlation with pathohistological findings in patients with adnexal masses. METHODS: Study involved 139 patients, 84 of them with benign, 47 with malignant and 8 with borderline adnexal tumor. Levels of CA 125, CA 19-9, CEA and CA 15-3 were obtained preoperatively and assessed regarding the specific pathohistological diagnose and the patient's age. Obtaining these results led us to divide the patient's CA 125 levels with age and by doing that we have attained a new Tumor Marker Age score (TMA score). RESULTS: Patients with malignant adnexal tumors had significantly higher levels of CEA (p<0.05), CA 125, CA 19-9 and CA 15-3 tumor markers (p<0.01), in comparison with patients with benign tumors. TMA score highly statistically correlate with the tumor type (benignant/malignant). CONCLUSIONS: With the increase of tumor marker levels and the patient's age the malignant nature of adnexal tumors is more often. Results of our study highlight the importance of the use of combined tumor markers (at least CA-125 and CA 19-9) in women with adnexal masses. Those levels along with the patient's age and new TMA score could preoperatively predict malignant nature of the tumor.

Hysterectomy for Treatment of CIN.

The objective of this investigation was to determine the percentage of microinvasive and invasive cancers found when CIN 3 was treated by hysterectomy. The postoperative histologic findings of all patients with CIN 3 treated by conization or hysterectomy were analyzed. In 295 patients treated by conization, 14 (4.75%) microinvasive and 11 (3.73%) invasive cancers were found. Histologic analysis of 106 hysterectomy specimens revealed microinvasive carcinoma in 11 (10.38%) and invasive carcinoma in 17 (16.04%) cases. The finding of unexpected invasive cervical cancer in hysterectomy specimens seems significantly higher compared with conization. One must be cautious to avoid hysterectomy as the primary mode of treatment for women with coincident uterine pathology, postmenopausal women, or those who do not desire further reproduction. Hysterectomy as a mode of treatment for CIN 3 should be performed only if the existence of invasive cancer was excluded with certainty.