ICTP concentration in cervical-vaginal fluid as a potential marker of membrane collagen degradation before labor.

OBJECTIVES: Numerous physical and chemical processes lead to rupture of membranes. Within the fetal membranes there are numerous types of metalloproteinases, which cause collagen type I degradation. The C-terminal telopeptide of colagen type I (ICTP) is the breakdown product of type I collagen. The aim of the study was to determine whether ICTP is secreted into the vaginal-cervical fluid (VCF) in the case of physiological rupture of the membranes of the fetus before delivery. MATERIAL AND METHODS: The study was conducted in March 2021 at the Department of Obstetrics and Perinatology of the Jagiellonian University in Cracow, Poland. Twenty-three cases were included in the study. During routine gynecological examination with the use of specula, VCF was collected twice in a volume of 50 µL. The obtained material was then subjected to enzyme immunoassay using the Human C-telopeptide of type I collagen (ICTP) ELISA Kit (Catalog Number. CSB-E10363h). The concentration of ICTP in the sample was calibrated. The concentration range that the device can detect was 25 ng /mL-800 ng/mL. RESULTS: The presence of ICTP in the VCF was confirmed. The minimum concentration was 43.72 ng/mL, the maximum was 762.59, in five cases the concentration was outside the maximum scale of the device. CONCLUSIONS: ICTP was confirmed in the VCF of pregnant women before physiological delivery. Further studies are required to accurately evaluate ICTP as a marker of the processes of collagen degradation in fetal membranes in the mechanism of physiological labor and premature rupture of the membranes.

The Assessment of the Usefulness of Prenatal Magnetic Resonance Imaging in the Diagnosis of Central Nervous System Defects.

Central nervous system (CNS) abnormalities cause about 40% of infant deaths in the first year of life. In case of the detection of abnormalities by ultrasound, a pregnant woman should be offered prenatal magnetic resonance imaging (pMRI). The aims of our study were: (1) to evaluate the effectiveness of pMRI in the diagnosis of selected fetal CNS defects; and (2) to assess the possibility of replacing postnatal tests with prenatal magnetic resonance. The prospective and observational study was conducted between 2014 and 2017 at the University Hospital in Krakow. Patients with suspected CNS defects of the fetus were qualified for pMRI in the third trimester of pregnancy. Sixty patients were included in the study group. Prenatal MRI was characterized by low accuracy in the diagnosis of complex brain defects. Cohen's kappa coefficient κ = 0.21 (95% CI 0.00-0.46). No evidence was found suggesting the replacement of postnatal tests with pMRI. MRI was characterized by low consistency of diagnoses in the case of complex brain defects. The possibility of replacing postnatal studies with pMRI was not supported.

The relevance of Short-Term Variation (STV) value measured within 1 hour before delivery in predicting adverse neonatal outcome.

OBJECTIVES: Computer CTG analysis (cCTG) included short-term variation (STV) is one of the methods of monitoring fetal condition during delivery. The aim of our study was to define appropriability of STV measured within 1 hour before delivery in prediction of neonatal outcomes. MATERIAL AND METHODS: The retrospective study included 1014 pregnant women, who gave birth in the Department of Obstetrics and Perinatology. Participants were divided into two groups: group 1 - term pregnancies (37-41 weeks) and group 2 - preterm pregnancies (lower than 37 weeks). In each of them, two subgroups have been separated: control (STV ≥ 3 ms) and study group (STV < 3 ms). RESULTS: In both groups 1 and 2, there were no statistically significant differences related to Apgar scores in 1st, 3rd and 5th minute between group with STV < 3 ms and group with STV > 3 ms Moreover, for 37-41 weeks the sensitivity, specificity, positive predictive value and negative predictive value were: 22.7%, 83.9%, 3.3% and 97.8% and for lower than 37: 45.7%, 65.4%, 47.1%, 64.2% in 1st minute after delivery. In group 1 the area under curve (AUC) measurements were 0.45 (95% CI: 0.32-0.58) for 1st minute and 0.55 (95% CI: 0.35-0.74) for 5th minute and in group 2: 0.58 (95% CI: 0.45-0.71) for 1st minute and 0.57 (95% CI: 0.42-0.72) for 5th minute. CONCLUSIONS: High specificity and negative predictive value of STV indicates a good Apgar score of newborns in term pregnancies. Analysis of STV in preterm pregnancy is not clear. Fetal well-being in preterm pregnancy should include STV and other non-invasive and invasive tools.

Magnetic resonance imaging of the fetal central nervous system: Timing and consistency between pre- and postnatal diagnoses.

INTRODUCTION: It has been shown that a proper comparison of prenatal ultrasound and magnetic resonance imaging (MRI) is possible only in the case of a short interval between tests. However, it is worth noting that the reference test is a postnatal examination. The aim of our study was to evaluate the effect of time between prenatal MRI (pMRI) and postnatal examinations on the consistency of diagnoses. MATERIAL AND METHODS: The prospective observational study was carried out between 2014 and 2017 at the Department of Obstetrics and Perinatology of Krakow University Hospital. In total, 60 patients with fetuses suspected of central nervous system (CNS) defects were included in the study group. PMRI examinations were conducted in the third trimester of pregnancy. RESULTS: The median gestational age of pMRI was 35 weeks and median of the time interval between carrying out pre- and postnatal test was 34.5 days. In the group of nonconcordant diagnoses, the interval was longer. The analysis did not show a statistically significant relationship between consistency of diagnoses and timing of pMRI. The median time of pregnancy at which pMRI was performed was similar in both groups. A prolongation of the interval between examinations reduced the probability of consistency of diagnoses. CONCLUSIONS: The number of inaccurate results increased with the prolongation of the interval between pre- and postnatal tests. KEY MESSAGE: Prolongation of the interval between pre- and postnatal increases number of inaccurate results.

Comparison of eleven commonly used formulae for sonographic estimation of fetal weight in prediction of actual birth weight.

OBJECTIVES: The aim of the study is to compare the accuracy of 11 formulas in predicting fetal weight. MATERIAL AND METHODS: The study includes 1072 pregnant women of gestational age from 28 to 42 weeks, who gave birth between January and June 2017. Pregnant women were divided into five groups; group 1, where actual birth weight (ABW) was less than 2500 g, group 2, where ABW was between 2500-4000 g, group 3, where ABW was above 4000 g. Group 4 - newborns with birth weight under 10 percentile and group 5 - newborns with birth weight above 90 percentile. The accuracy of the estimated fetal weight (EFW) was assessed by calculating absolute percentage error (APE) and 'limits-of-agreement'. R Spearman correlation was utilized between EFW and ABW. RESULTS: The most accurate formula for group 1 is Hadlock3 (MAPE = 7.04%), the narrowest limits of agreement has Combs - [mean (SD): 99.41 g (269.57 g)]. For group 2, the lowest MAPE (5.43%) has Ott, the narrowest limits of agreement belongs to Combs - [mean (SD): -101.36 g (275.88 g)] . For group 3 is Hadlock3 (MAPE = 5.79%), the narrowest limits of agreement has Hadlock5 [mean (SD): -637.32 g (209.59 g)]. For group 4 is Combs (MAPE = 7.72%), the narrowest limits of agreement has Combs [mean (SD): 195.77 g (264.97 g)]. For gr oup 5 is Warsof2 (MAPE = 7.06%), the narrowest limits of agreement has Campbell [mean (SD): 227.81 g (299.26 g)]. CONCLUSIONS: Median of absolute percentage error is the most useful parameter to predict birth weight. Each group of fetuses needs different formula to predict the most accurate weight.

Evaluation of Pregnancy Outcomes at Advanced Maternal Age.

AIM: The study aimed to investigate the association between advanced maternal age (AMA) and the risk of adverse maternal, perinatal and neonatal outcomes about parity in singleton pregnancies. METHODS: We retrospectively analysed 950 women who gave birth in the Department of Obstetrics and Perinatology of the University Hospital in Kraków for six months (between 1st January and 30th June 2018). The patients were divided into 3 groups according to their age (30-34 years old, 35-39 years old and over 40 years old). Each of these groups was subsequently subdivided into 2 groups depending on parity (primiparae and multiparae). Maternal, perinatal and neonatal outcomes were compared between the groups and the subgroups. RESULTS: Comparison of the three age groups revealed that advanced maternal age might constitute a predisposing factor for preterm birth, caesarean section and large for gestational age (LGA). From these parameters, statistical significance was reached in case of greater risk of LGA (OR = 2.17), caesarean section (OR = 2.03) and elective C-section (OR = 1.84) in women over 40 years old when compared to the patients aged 30-34. Furthermore, AMA increases the risk of postpartum haemorrhage (OR = 6.43). Additionally, there is a negative correlation between maternal age and gestational age at delivery (R = -0.106, p < 0.05). CONCLUSIONS: Advanced maternal age can undoubtedly be associated with several adverse perinatal outcomes. At the same time, the risk of perinatal complications begins to increase after the age of 35 but becomes significant in women aged ≥ 40.

Effect of oligohydramnios on the accuracy of sonographic foetal weight estimation in at term pregnancies.

OBJECTIVE: Ultrasound estimation of foetal weight is a very important aspect of antenatal care. The role of amniotic fluid volume as a potential factor which may impede the relevance of ultrasonographic foetal weight estimation is still questionable. The aim of our study was to evaluate the impact of isolated oligohydramnios on the accuracy of ultrasound foetal weight estimation in at term pregnancies when examination was performed within 48 h before delivery. MATERIALS AND METHODS: The retrospective cohort study included 1831 women with low-risk, singleton, at term pregnancy. Estimated foetal weight (EFW) was calculated using Hadlock-4 formula. Exclusion criteria consisted of multiple pregnancies, active phase of labour, preeclampsia, foetal growth restriction, foetal anomalies, gestational diabetes mellitus and the evidence of intrauterine infection. Isolated oligohydramnios was defined as Amniotic Fluid Index (AFI) ≤50 mm without any other foetal anomalies. EFW and actual birth weight (ABW) were compared by calculation of: absolute error (AE), absolute percentage error (APE) and substantial error (SE) = APE >10%. RESULTS: Participants were divided into 2 groups: Group 1: patients with normal AFI (50 ≤ AFI ≤250 mm; n = 1602) and Group 2: (isolated oligohydramnios, n = 229). There were not observed statistically significant differences between mean ABW and mean EFW in both groups (Group 1: p = 0.525; Group 2: p = 0.317). Mean AE in Group 1 was 221.8 g and 223.1 g in Group 2 (p = 0.919). Mean APE was 6.54% and 6.64% in Group 1 and 2 respectively (p = 0.816). SE ratio was 21.9% in Group 1 and 19.2% in Group 2. Underestimation to overestimation ratio in Group 1 was 1.01 and 0.84 in Group 2. CONCLUSIONS: Amniotic fluid volume has limited impact on ultrasound foetal weight estimation. In oligohydramnios group there might be a tendency of overestimation of neonatal ABW.

The relationship between pre-pregnancy BMI, gestational weight gain and neonatal birth weight: a retrospective cohort study.

OBJECTIVES: Maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) have a meaningful impact on pregnancy and perinatal outcomes. The first aim of the study was to analyze the association between pre-pregnancy BMI and the prevalence of small for gestational age (SGA) and large for gestational age (LGA) outcomes. The second aim was to assess the relation- ship between pre-pregnancy BMI combined with gestational weight gain (GWG) and the prevalence of SGA and LGA measurements. MATERIAL AND METHODS: The retrospective cohort study was conducted at Jagiellonian University Hospital in Cracow, Po- land from 2016 to 2017. During this time there were 2,123 deliveries. Patients with chronic diseases, multiple pregnancies, fetal defects and incomplete data were excluded. Finally, 474 cases were enrolled. Patients were divided into BMI groups (underweight, normal, overweight and obese) and into GWG groups (inadequate, adequate, excessive). Relationships between maternal BMI, GWG and newborn weight were examined. RESULTS: There was no statistically significant association between maternal pre-pregnancy BMI and prevalence of SGA measurements. However, underweight women with inadequate GWG showed a higher risk to bear SGA babies (OR 5.2, 95% CI 1.57-17.18). Obese women with adequate GWG had higher risk of bearing LGA newborns (OR 5.48, 95% CI 1.15-26.13). High BMI correlated with excessive GWG (overweight: OR 3.0, 95% CI 1.84-3.87; obese OR 2.45, 95% CI 1.1-5.48). CONCLUSIONS: There is a considerable risk of giving birth to a SGA newborn for underweight women with inadequate GWG. There is a statistically significant association between maternal obesity and LGA outcomes. Our study shows that redefining the risks of abnormal neonatal weight considering both pre-pregnancy BMI and gestational weight gain can be useful in providing effective prevention during pregnancy.

Labor induction at full-term and post-term pregnancies.

INTRODUCTION: Induction of labor is an intervention in the obstetrics, which aim is to achieve cervical ripening and stimulate contractions of uterus before beginning of labor. The purpose of our study was to evaluate efficacy of combinations of vaginal misoprostol, intracervical dinoprostone and Foley catheter at term with regard to mode of delivery and rate of emergency C-sections due to birth asphyxia. MATERIAL AND METHODS: 403 singleton pregnant women, who underwent pharmacological labor induction at term, were reviewed. Patients were divided into 2 main cohorts due to beginning of induction algorithm: vaginal misoprostol (66) or intracervical dinoprostone (337) consisting of 3 subgroups - PGE2 alone (184), PGE2+Foley catheter (125), PGE2+Foley catheter+PGE1 (28). RESULTS: Comparison of maternal age, presence of cervical dilation and parity revealed no major differences between cohorts. Effectiveness of labor induction with misoprostol, dinoprostone and dinoprostone followed by Foley catheter were respectively 90.9%, 51.3%, and 82.8%. Addition of PGE1 was effective in 83% of patients with negative response to PGE2 followed by Foley catheter. ere was no statistically significant difference in rate of C-sections between dinoprostone and misoprostol cohorts, C-section due to birth asphyxia were insignificantly more frequent in PGE1 than in PGE2 cohort. Efficacy in the subgroup administered only dinoprostone was significantly higher in 40th than in 41th (p = 0.016). CONCLUSIONS: Intracervical dinoprostone seems to be safer, but less effective in labor induction than vaginal misoprostol. Following PGE2 by other methods increased efficacy of induction in this cohort.

Relaparotomy following cesarean section - a single center study.

INTRODUCTION: Relaparotomy is a serious complication of caesarean section. The aim of this study was to investigate its risk factors and postoperative outcome. METHODS: We conducted a retrospective case-control study examining 48 reoperations between January 2013 and June 2017 at the Obstetrics and Perinatology Department, Jagiellonian University Hospital in Cracow, Poland. This is tertiary referral center, in that time 8421 cesarean section were performed. The control group was randomly matched from all CS in a 1 to 2 ratio. The following figures were analyzed: demographic obstetrics data, indication for cesarean section, perioperative data and laboratory results. Patients' follow up data was evaluated. RESULTS: The frequency of relaparotomy was 0.57%. There were no statistically significant differences in indications for primary surgery between the control group and the relaparotomy group. There were only two perioperative factors which increased the risk of relaparotomy: general anesthesia and the duration of operation. Laboratory results were in reference range in both groups, however, in the relaparotomy group, platelets were lower, while APTT and INR were prolonged. The main indication for relaparotomy was bleeding into the peritoneal cavity. Patients with relaparotomy more often required blood transfusion, admission to ICU, as well as longer hospitalization. CONCLUSION: Recognition of risk factors of relaparotomy and proper diligence in hemostasis may decrease its rate.

Telocytes in the female reproductive system: An overview of up-to-date knowledge.

Telocytes are emerging cell population localized in the stroma of numerous organs, characterized by a distinctive morphology - small cell body with very long, slender prolongations, termed telopodes. Those cells can be found in the whole female reproductive system: in the vagina, uterus, oviducts and ovaries, mammary glands and also in the placenta. In our review, we aim at complete and transparent revision of the current knowledge of telocytes' localization and function, enriched by the analysis of the possible future direction of development of their clinical applications. The function of telocytes in the reproductive system has not been fully elucidated yet; however, many researchers point at their role in the regulation of local microenvironment, myogenic contractile mechanism, bioelectrical signaling, immunomodulation and regulation of blood flow. Additionally, previous research suggests that telocytes might act as sex hormone level sensors and are connected with pregnancy maintenance. As the morphology and number of those cells change under pathological conditions, such as pre-eclampsia, endometriosis and ovarian failure, there is a chance that they may contribute to therapy of abovementioned conditions. The impact of telocytes on stem cells and angiogenesis has been proven in many organs, and may be useful in regenerative medicine of the female reproductive system. A recently found connection between the proliferation rate of breast cancer cells and stromal cells like telocytes might be a step forward to the management of mammary gland neoplasms.

Screening performance for callosal agenesis in prenatal life. Single center study.

OBJECTIVES: 1) To analyze screening performance of second trimester scan for ACC, 2) to evaluate the agreement between ultrasound and MRI and 3) to compare prenatal and postnatal diagnosis. METHODS: It was a prospective observational study. All patients with fetuses suspected of ACC were referred to prenatal MRI (pMRI). RESULTS: One subject was not confirmed by pMRI with the diagnosis of ACC. This case demonstrated partial ACC in neonatal MRI (nMRI). CONCLUSION: Sensitivity of second trimester scan for callosal agenesis of 73% and specificity of 99%. Prenatal MRI and US has similar amount of misdiagnoses.

Assessment of the implementation of the infectious diseases screening programmes among pregnant women in the Lesser Poland region and comparison with similar programmes conducted in other European Union countries.

OBJECTIVES: The aim of the study was to assess the level of implementation of recommendations of the Ministry of Health regarding infectious disease screening during pregnancy. MATERIAL AND METHODS: The study included 477 patients who were admitted to the delivery room between December 2015 and February 2016. Data on screening test results were collected based on medical records covering the period before the admission. RESULTS: The Human Immunodeficiency Virus (HIV) screening was conducted in 410 (86%). 460 (96%) of patients were screened for Hepatitis B Virus (HBV) and 427 (89.5%) for Hepatitis C Virus (HCV). Syphilis screening covered 465 (97.5%) of patients. Immunoglobulin M (IgM) titer against Rubella Virus (RV) was assessed in 218 (45%) patients and immunoglobulin G (IgG) in 319 (66.9%). Screening for Toxoplasma gondii based on assessment of IgM titer was conducted in 440 (92%) patients while IgG titter was assessed in 413 (86.6%). 343 (71.9%) patients had obtained vaginal swabs for Group B Streptococci (GBS) while the anal swabs were taken only from 268 (56.2%) patients. CONCLUSIONS: Coverage of screening for syphilis and HBV was similar to the countries with highest prevalence of conducting such screening, on the other hand RV screening place as among countries with lowest prevalence. There is an increasing trend in conducting HIV screening. Screening for HCV and toxoplasmosis is at satisfactory level and Poland is one of a few European countries offering such screening. The screening for GBS is insufficient which result in excessive use of intrapartum antibiotic prophylaxis.

Autosomal dominant polycystic kidney disease diagnosed in utero. Review.

Autosomal dominant polycystic kidney disease (ADPKD) is one of most common inherited renal diseases. It is estimated that very early onset ADPKD affects even 2% patients. The purpose of this article is to provide a comprehensive review of genetics, prenatal diagnosis and prognosis in very early onset autosomal dominant polycystic kidney disease.

[An influence of changes in the levels of leptin on the risk of preterm delivery in patients with excessive BMI].

Introduction: In the literature are found in only a few reports on the role of leptin in the etiology of preterm birth in pregnant women with excessive BMI. The aim of the study was to evaluate the relationship between leptin levels and the prevalence of symptoms of preterm labor as well as assessment of changes in leptin levels depending on the BMI and the effect of leptin on the state of postnatal neonatal determined by Apgar scale. Material and method: Prospective analysis applied to the data obtained from 80 patients hospitalized in the Department of Obstetrics and Perinatology University Hospital in Cracow. The study was prospective and cohort. The study included pregnant single diagnosed with a BMI greater than or equal to 25. Results: It had significantly higher levels of leptin in the group of patients with symptoms of pre-term labor and BMI≥25 compared to lower concentrations of leptin from the group of patients with a BMI <25 (p = 0.01414). It has been found higher levels of plasma leptin in patients with BMI≥25 compared to patients with a BMI <25, in the groups of patients during the nascent (0.0492). Conclusions: Pregnant with symptoms of preterm labor and excessive BMI had higher levels of leptin than women giving birth on time with abnormal, excessive BMI. It was found higher levels of leptin in the group of patients with symptoms of pre-term labor in comparison to the control groups, which may favor the severity of inflammation which is the cause of the symptoms of preterm labor. There was no correlation between the changes in leptin levels during pregnancy and the state natal infants based on the Apgar scale.

[Intrauterine growth restriction--diagnosis and treatment]. / Wewnatrzmaciczne zahamowanie wzrastania plodu--diagnostyka i postepowanie.

The prevalence of low birth weight affects approximately 3-10% of live-born newborns in developed countries and in developing countries it affects 15-20% of newborns. The most common cause of low birth weight is considered to intrauterine fetal growth resctriction. Low birth weight is responsible for 69.6% of stillbirths and for 66.4% of neonatal deaths. The purpose of this paper is to review reliable scientific data in order to summarize the current guidelines on intrauterine fetal growth restriction, addressed to obstetricians. The present review is based on guidelines of the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), the results of DIGITAT- (ang. The Disproportionate Growth intrauterine Intervention Trial At Term) PORTO Study- (ang. Prospective Observational Trial is the Opitimize Pedriatric Health in intrauterine Growth Restriction), TRUFFLE- (ang. Randomized Trial of Fetal and Umbilical Flow in Europe), and the available literature.

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.

Hormone replacement therapy regimens in chemotherapy-induced premature ovarian failure and the subsequent correction of hormone levels.

OBJECTIVES: Premature ovarian failure (POF) is a consequence of gonadotoxic chemoradiotherapy given in antyneoplasia treatment. In young women it will correlate with menopausal symptoms which tend to appear due to depleted ovarian follicle reserve. DESIGN: It was a case series study that included women 18-50 years old who were treated for malignancy with gonadotoxic chemioradiotherapy. We have measured blood hormonal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone within one month of various hormone replacement therapy (HRT). RESULTS: We have observed different kind of hormonal reaction according to FSH, LH, estradiol and progesterone levels due to various hormonal replacement therapy. The administration of various HRT regimens presented with a decrease in the blood concentration of estradiol E2 and progesterone and a concomitant increase of FSH and LH. These findings demonstrate a shift to physiological ranges and a simultaneous improvement of symptoms associated with CI-POF. CONCLUSIONS: The most appropriate therapy needs to be selected according to the patient's alleviation of symptoms and correction of blood hormone levels.

Solid papillary carcinoma of the breast with neuroendocrine features in a pregnant woman: a case report.

Solid papillary carcinoma, a special form of breast carcinoma with neuroendocrine differentiation, usually presents in women aged 60 years or more. (Koern 2010). According to our best knowledge, we present the second case of such a tumor in pregnant women.

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.