Hubert Huras

Stratification of HPV-induced cervical pathology using the virally encoded molecular marker E4 in combination with p16 or MCM

High-risk human papillomavirus (HPV) types cause cervical lesions of varying severity, ranging from transient productive infections to high-grade neoplasia. Disease stratification requires the examination of lesional pathology, and possibly also the detection of biomarkers. P16INK4a and MCM are established surrogates of high-risk HPV E6/E7 activity, and can be extensively expressed in high-grade lesions. Here we have combined these two cellular biomarkers with detection of the abundant HPV-encoded E4 protein in order to identify both productive and transforming lesions. This approach has allowed us to distinguish true papillomavirus infections from similar pathologies, and has allowed us to divide the heterogeneous CIN2 category into those that are CIN1-like and express E4, and those that more closely resemble nonproductive CIN3. To achieve this, 530 lesional areas were evaluated according to standard pathology criteria and by using a multiple staining approach that allows us to superimpose biomarker patterns either singly or in combination onto an annotated hematoxylin and eosin (H&E) image. Conventional grading of neoplasia was established by review panel, and compared directly with the composite molecular pathology visualized on the same tissue section. The detection of E4 coincided with the onset of vacuolation, becoming abundant in koilocytes as the MCM marker declined and cells lost their defined nuclear margins as visualized by standard H&E staining. Of the dual marker approaches, p16INK4a and E4 appeared most promising, with E4 generally identifying areas of low-grade disease even when p16INK4a was present. Extensive p16INK4a expression usually coincided with an absence of E4 expression or its focal retention in sporadic cells within the lesion. Our results suggest that a straightforward molecular evaluation of HPV life-cycle deregulation in cervical neoplasia may help improve disease stratification, and that this can be achieved using complementary molecular biomarker pairs such as MCM/E4 or, more promisingly, p16INK4a/E4 as an adjunct to conventional pathology.

Leptin and interferon-gamma as possible predictors of cesarean section among women with hypertensive disorders of pregnancy

Summary Background This study was designed to evaluate maternal levels of leptin and interferon-gamma (IFN-gamma) in pregnancy complicated with hypertension and to assess the role of cytokines in predicting the risk of cesarean section. Material/Methods This was a cohort study with a prospective follow-up. After proportional sampling procedure, the study included the follow-up of 40 women with hypertensive disorders of pregnancy (pregnancy-induced hypertension [PIH] or preeclampsia [PE]) and 40 uncomplicated pregnancies. Women were followed from the time of admission to the delivery. Levels of leptin and interferon-gamma were measured in serum samples from all women. A p-value <0.05 was considered as significant. Results Significant increase in IFN-gamma and leptin concentration in women with pre-eclampsia was observed. We found a significant 1.4-fold increase in the risk of birth by cesarean section associated with the increase of the IFN-gamma concentration by 0.1 pg/ml and almost 3-fold increase in the risk associated with the increase of the leptin concentration. Conclusions IFN-γ and leptin might be risk markers of cesarean section in hypertension disorders of pregnancy, but further studies supporting this evidence are needed.

Multiple Myeloma in Pregnancy—A Review of the Literature and a Case Series

Multiple myeloma (MM) typically affects older patients with a median age at diagnosis of 67 to 70 years and only 3% of cases are diagnosed before the age of 40. Moreover, MM is more common in men. Therefore, pregnancy rarely occurs in patients with MM and only 37 cases of MM in pregnancy have been reported in the literature. Herein we report an additional 5 cases. The diagnosis of MM might be problematic in this context because some of the symptoms and signs, such as back pain and anemia, can be attributed to pregnancy. Furthermore, if the patient wishes to continue her pregnancy, therapeutic options are currently limited. The list of agents that can be safely administered in pregnant women includes glucocorticoids. Moreover, any continuation of pregnancy has obvious long-term psychosocial repercussions for the patient and her family because of the currently incurable nature of MM. The reported cases of MM in pregnancy represent a spectrum of clinical manifestations. The selection of efficacious and safe treatments is challenging, especially if continuation of pregnancy is desired. Although some authors postulate that pregnancy might lead to progression of MM, data are limited and no consensus on this point has been reached.

Expression of Vascular Endothelial Growth Factors VEGF- C and D, VEGFR-3, and Comparison of Lymphatic Vessels Density Labeled with D2-40 Antibodies as a Prognostic Factors in Vulvar Intraepithelial Neoplasia (VIN) and Invasive Vulvar Cancer

OBJECTIVE The aim of this study was to compare the immunohistochemical expression of vascular endothelial growth factors VEGF-C and D, as well as the expression of VEGFR-3 in VIN and vulvar invasive cancer and to compare the density of lymphatic marker D2-40 antibody in both groups, and to compare them with different clinicopathologic features. MATERIALS & METHODS The study was performed using tissue material and clinical data from 100 women diagnosed with VIN and 100 women diagnosed with invasive vulvar cancer. RESULTS No significant differences were found in the expression of VEGF-C and -D or VEGFR-3 between those patients with VIN and those with invasive vulvar cancers. Weak expression of VEGF-C was confirmed only in two cases of the analyzed series; in all cases, expression of VEGF-D and VEGFR-3 was observed. The strongest expression of VEGF-D and VEGFR-3 was observed in the group of invasive cancers. The highest density of lymphatic vessels per 2 mm was observed in VIN. In the cancer group, small lymphatic vessels with a narrow oval lumen were observed. Moreover, in two cases of vulvar cancer, the presence of intratumoral lymphatic vessels was observed. CONCLUSIONS These results suggest that lymphangiogenesis begins at the preinvasive stage of vulvar carcinogenesis and suggests the important role of VEGF-C, VEGF-D, VEGFR-3 and LV (D2-40) as prognostic factors in the process of carcinogenesis in the vulvar area.

Analysis of intravaginal misoprostol 0.2 mg versus intracervical dinoprostone 0.5 mg doses for labor induction at term pregnancies

OBJECTIVES Labor-induction methods are used in about 23% of labors. Most commonly, pharmacological methods are used to pre-induct the labor with dinoprostone - a PGE2 analog, and misoprostol - a PGE1 analog. The aim of this study was to evaluate two pharmacological methods of labor induction with the use of prostaglandins applied via an intravagi-nal insert containing misoprostol at a dose of 0.2 mg and intracervical gel containing dinoprostone at a dose of 0.5 mg. MATERIAL AND METHODS This retrospective study was conducted on a group of 50 adult patients qualified for the pre-induction of labor. Following data were recorded: the time from the drug administration to the beginning of regular contractile function, the time from administration to amniotic fluid rupture, the time from medicament administration to the vaginal labor or caesarean section, the duration of I, II and III stages of labor, the delivery method and in the event of caesarean section - the indications for surgery. RESULTS In comparison to dinoprostone, the misoprostol application was found to shorten the time from drug administration to amniotic fluid rupture by 14.1 hours, the time to the beginning of the first stage of labor by 11.7 hours and from the drug administration to the delivery by 17.3 hours (p-value < 0.05). The duration of the first stage of labor in the misoprostol group was shorter by 1.2 hours than in dinoprostone group (p-value < 0.05). CONCLUSIONS Application of intravaginal insert with misoprostol at a dose of 0.2 mg appears to be a more effective method of labor induction in comparison to intracervical gel with dinoprostone at a dose of 0.5mg. Thorough analysis of these methods requires further studies.

Recurrent vulvar melanoma in 35-year-old pregnant women.

Vulvar melanoma represents between 3% and 10% of vulvar neoplasms. We present a case of a 34-year-old pregnant woman presenting with a pigmented lesion on the left labium majus; she reported no family history of melanoma. The histological diagnosis was malignant melanoma, superficial spreading type, with Breslow thickness of 0.9 mm; the excision was complete. Eight months before, an atypical genital nevus was completely excised from a nearby location. The pregnancy was finished by cesarean delivery at term, and 3 months later, another pigmented lesion was noticed near but not within the scars. Partial right vulvectomy was performed, and histological diagnosis was malignant melanoma of superficial spreading type, with Breslow thickness of 0.7 mm. The specimen obtained in the first operation was reviewed, and although histological examination was diagnostic for atypical genital nevus, Vysis Melanoma Fluorescence in situ hybridization Probe Kit revealed increased copy numbers of RREB1, which could be consistent with a diagnosis of malignant melanoma.

The significance of a prenatal diagnosis of right aortic arch

To analyze a population of fetuses with prenatally diagnosed right aortic arch (RAA).

Low-Grade Metabolically-Induced Inflammation Mediators Interleukin-6, Adiponectin, and TNF-α Serum Levels in Obese Pregnant Patients in the Perinatal Period

Background Obesity is a major clinical problem. The number of obese pregnant women is rising rapidly. The consequences of obesity are significant and affect every aspect of perinatal care for both the mother and the developing fetus. Adipose tissue may be responsible for chronic subclinical inflammation in obesity, being a source of inflammatory mediators. The study was designed to evaluate the analysis of the serum concentration of inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and adiponectin, in obese pregnant women at full-term pregnancies. Material/Methods The study included 40 women with body mass index (BMI) less than 30 and 24 pregnant women with BMI equal to or greater than 30, admitted to the Perinatology and Obstetrics Department of the University Hospital in Cracow in the first stage of labor. Blood samples were taken from patients to detect the serum concentration of cytokines. Ultrasound was used to evaluate the development of the fetus, including estimated fetal weight, Doppler flows, and the amount of amniotic fluid. We also included the history of chronic diseases and other complications of the pregnancy. A p-value <0.05 was considered significant. Results The level of adiponectin in obese patients as compared to controls was significantly lower. There was no statistically significant difference in either group when TNF-α and IL-6 were measured. The results of the survey are consistent with previous reports. Conclusions The exact role of inflammation in pregnancy is not well understood. Determining the exact functions of the different cytokines in physiological pregnancy and pregnancy complicated by obesity requires further study.

Evaluation of the fetal palate at 11 to 13 (+6) weeks of gestation based on an analysis of static ultrasound images using modern IT techniques

To describe a new computer‐based technique to isolate the shape of the fetal palate visible in the midsagittal plane from static ultrasound images routinely used to measure nuchal translucency.

Neurocutaneous melanosis in a newborn identified prenatally by non-invasive imaging

Dermatology Review/Przegląd Dermatologiczny 2018/4 A 21-year-old pregnant woman (gravida 1 para 1) was referred to the Department of Obstetrics and Perinatology for sonographic examination, which revealed a fetus at 29 + 6 weeks with an irregular cystic-solid subcutaneous mass of heterogeneous echogenicity (16 × 10 × 9 cm in size) covering the surface of both shoulders and the dorsal chest wall (fig. 1). No increase in tumor size was detected up to the delivery. The neonate was a boy, born in good condition by cesarean section after 39 weeks of gestation. At birth, he was found to have multiple congenital melanocytic nevi. An extensive nevus was noted on the trunk, covering the thorax, loins, buttocks and both thighs, having a circumferential distribution. It was hairy and partially composed of large, elevated tubers (figs. 2, 3). Because of the suspicion of neurocutaneous melanosis (NCM), the newborn was given an magnetic resonance imaging (MRI) examination which showed the presence of multiple hiperintense lesions, from 3 to 6 mm in diameter, in the cerebellum, medulla oblongata, the enteral part of the pons, left thalamus, calcarine sulcus, and in the parietal-occipital sulcus. Skin biopsy revealed a melanocytic proliferation Letter to the editor/List do Redakcji