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1.
J Matern Fetal Neonatal Med ; 37(1): 2326304, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38499386

ABSTRACT

OBJECTIVE: Endothelial dysfunction is a major feature of preeclampsia. sVE-cadherin plays a role in the preservation and regulation of the endothelial barrier. For that reason, to evaluation of sVE-cadherin may help elucidate the disease pathophysiology of preeclampsia. METHODS: The sample size was calculated as a minimum of 46 pregnant women for each group based on serum sVE-Cadherin levels in a pilot study of 10 preeclamptic and 10 control groups. Hundred-twenty pregnancies complicated with early-onset (n = 60) and late-onset (n = 60) preeclampsia were compared with 120 gestational-age (GA)-matched (±1 week) uncomplicated pregnancies. The venous blood sampling was performed upon preeclampsia diagnosis prior to the onset of the labor in the preeclampsia group and the matching (±1 week) pregnancy week in the control group. Demographic and biochemical parameters were evaluated. RESULTS: Mean serum sVE-Cadherin was significantly higher in women with EOPE compared to that of the GA-matched control group (5.86 ± 1.57 ng/mL vs. 2.28 ± 0.80 ng/mL, p < 0.001), in women with LOPE compared to that of the GA-matched control group (3.11 ± 0.97 ng/mL vs. 1.69 ± 0.87 ng/mL, p < 0.001), and in women with EOPE compared to that of LOPE group (5.86 ± 1.57 ng/mL vs. 3.11 ± 0.97 ng/mL, p < 0.001) after correction for GA. Serum sVE-Cadherin positively correlated with systolic and diastolic blood pressure and a negative correlation with gestational age at sampling. CONCLUSION: The serum level of sVE-Cadherin was higher in women with preeclampsia than that of GA-matched healthy pregnant women, in women with EOPE compared to that of LOPE. sVE-Cadherin is an important marker in early-onset pre-eclampsia with severe clinical findings.


Subject(s)
Eosine Yellowish-(YS)/analogs & derivatives , Phosphatidylethanolamines , Pre-Eclampsia , Pregnancy , Humans , Female , Pilot Projects , Blood Pressure , Case-Control Studies , Cadherins
2.
Z Geburtshilfe Neonatol ; 228(2): 166-173, 2024 Apr.
Article in German | MEDLINE | ID: mdl-38081217

ABSTRACT

INTRODUCTION: The management of pregnant women at risk of preterm delivery poses a challenge to the interdisciplinary team. At the edge of viability, it is crucial to take into consideration maternal and fetal risk factors when determining individual counseling and therapeutic approaches. METHODS: At a level 4 perinatal center, all preterm infants (PI) born in the years 2017 to 2020 who had a gestational age between 230/7 and 246/7 weeks and were cared for with a curative therapeutic approach were enrolled in a retrospective observational study. Divided into two groups (230/7-236/7 and 240/7-246/7 weeks of gestation), the PI were compared in terms of mortality and morbidity based on maternal and fetal risk factors. Thirteen risk factors and their prognostic relevance for survival were analyzed. RESULTS: 41 mothers with 48 PI were included. 9 neonates received primary palliative treatment and were excluded from the analyses. The survival rates between the two groups (n=21, n=27) showed no significant difference (66.7% versus 74.1%, p=0.750). A significantly higher mortality was observed in PI with an increased number of risk factors (p=0.004), the most severe of which were hypertensive disorders of pregnancy and preterm premature rupture of membranes. Data regarding morbidity showed no significant difference. CONCLUSION: Data regarding mortality correlate with national findings. Observed morbidity in the study population was recorded. The prediction of probability of survival is more precise when risk factors are taken into consideration.


Subject(s)
Fetal Membranes, Premature Rupture , Premature Birth , Female , Humans , Infant , Infant, Newborn , Pregnancy , Fetal Membranes, Premature Rupture/epidemiology , Gestational Age , Infant, Extremely Premature , Morbidity , Risk Factors , Retrospective Studies
3.
J Reprod Immunol ; 154: 103763, 2022 12.
Article in English | MEDLINE | ID: mdl-36399874

ABSTRACT

COVID-19 is a multisystem disease and cause of a global pandemic. Lately, cases of disease progression of HPV-infected CIN under SARS-CoV-2 infection were reported giving rise to the hypothesis of direct virus-infection induced pro-carcinogenic effect of SARS-CoV-2. We herein present a case of rapid progression from HPV-induced CIN 2 to microinvasive carcinoma within three months under COVID-19 without direct virus infection. Histopathologic evaluation, Fluorescence-in-situ hybridization and qRT-PCR against SARS-CoV-2 RNA as well as gene expression analysis were performed from the available FFPE-tissue and accompanied by an analysis of white blood cell differential. No signs of direct SARS-CoV-2 infection or COVID-19 typical alterations of cervical tissue were found. As expected, p53 decreased in expression with progression of dysplasia, while APOBEC3A and VISTA showed a decrease in expression contrary to observations in dysplasia progression. PD-L1 was expressed consistently or increased slightly but did not show the expected strong induction of expression. DNMT1 showed an increase in expression in CIN III and a slight decrease in carcinoma, while DNMT3a is consistently expressed in CIN II and decreased in carcinoma. Blood tests after COVID-19 showed substantial reduction of lymphocytes, eosinophils, T-cells, and NK-cells. Our results hint at an indirect effect of COVID-19 on the cervical neoplasm. We conclude that the immune system might be preoccupied and exhausted by the concurring COVID-19 disease, leading to less immunological pressure on the HPV-infected cervical dysplasia enabling rapid disease progression. Further, indirect proangiogenic and proinflammatory micromilieu due to the multisystemic effects of COVID-19 might play an additional role.


Subject(s)
COVID-19 , Papillomavirus Infections , Uterine Cervical Dysplasia , Female , Humans , SARS-CoV-2 , Papillomavirus Infections/complications , RNA, Viral , Leukocytes , Disease Progression
5.
Z Geburtshilfe Neonatol ; 226(3): 178-185, 2022 06.
Article in English | MEDLINE | ID: mdl-35181881

ABSTRACT

OBJECTIVE: To evaluate the serum vasostatin-1 levels in preeclamptic and non-preeclamptic pregnant women. MATERIALS AND METHODS: Thirty consecutive women with mild preeclampsia and sixty consecutive women with severe preeclampsia were compared with ninety gestational age-matched (±1 week) non-preeclamptic pregnant women with an appropriate-for-gestational-age (AGA) fetus. RESULTS: Mean serum vasostatin-1 was significantly higher in women with preeclampsia than gestational age-matched controls. Mean serum vasostatin-1 was significantly higher in the mild preeclampsia group compared to its gestational age-matched control group, and in the severe preeclampsia group compared to its gestational age-matched control group. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups, and in severe early- and severe late-onset preeclampsia groups. Serum vasostatin-1 had positive correlations with systolic and diastolic blood pressure. CONCLUSION: Serum vasostatin-1 was significantly higher in women with preeclampsia compared to those of the gestational age-matched controls. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups and severe early- and severe late-onset preeclampsia groups.


Subject(s)
Chromogranin A , Peptide Fragments , Pre-Eclampsia , Blood Pressure/physiology , Case-Control Studies , Chromogranin A/blood , Female , Gestational Age , Humans , Peptide Fragments/blood , Pre-Eclampsia/diagnosis , Pregnancy
6.
J Obstet Gynaecol ; 42(1): 55-60, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33938370

ABSTRACT

Catestatin can inhibit catecholamine release from chromaffin cells and adrenergic neurons. Catestatin can also have a strong vasodilator effect. This may be useful in understanding the pathophysiology of preeclampsia and its treatment. In this study, we investigated the serum catestatin levels in pregnant women with and without preeclampsia. Fifty consecutive women with mild preeclampsia, 50 consecutive women with severe preeclampsia, and 100 consecutive pregnant women with a gestational age-matched (±1 week) uncomplicated pregnancy were evaluated in a cross-sectional study. Mean serum catestatin was significantly increased in the preeclampsia group compared to the control group (290.7 ± 95.5 pg/mL vs. 182.8 ± 72.0 pg/mL). Mean serum catestatin was comparable in mild and severe preeclampsia groups (282.7 ± 97.9 pg/mL vs. 298.7 ± 93.4 pg/mL, p = .431). Serum catestatin levels had positive correlations with systolic and diastolic blood pressure, urea, uric acid, and creatinine. In conclusion, serum catestatin levels are increased in preeclamptic pregnancies compared to gestational age-matched controls.IMPACT STATEMENTWhat is already known on this subject? The role of autonomic nervous system dysregulation in the pathophysiology of preeclampsia is known. The most obvious part of this dysregulation is the sympathetic nervous system activation. The adrenal medulla is one of the locations of the sympathetic nervous system in the body.What do the results of this study add? Serum catestatin levels were found to be correlated with clinical and laboratory data of preeclampsia. This highlights the importance of chromaffin cell secretions in the adrenal medulla in preeclampsia.What are the implications of these findings for clinical practice and/or further research? This study will help understand the role of the adrenal medulla in the autonomic nervous system dysregulation in preeclampsia. Also, control of serum catestatin levels may support the treatment of hypertension in preeclampsia.


Subject(s)
Chromogranin A/blood , Peptide Fragments/blood , Pre-Eclampsia/blood , Adult , Blood Pressure , Case-Control Studies , Creatinine/blood , Cross-Sectional Studies , Female , Gestational Age , Humans , Pregnancy , Urea/blood , Uric Acid/blood
7.
Taiwan J Obstet Gynecol ; 60(5): 869-873, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34507663

ABSTRACT

OBJECTIVE: To evaluate the possible associations between serum Neprilysin (NEP) levels and preeclampsia and mild and severe preeclampsia subgroups. MATERIALS AND METHODS: Fifty-five consecutive women with mild preeclampsia and fifty-five consecutive women with severe preeclampsia were compared with 110 approximately gestational age-matched (±1 week) women with an uncomplicated pregnancy. RESULTS: Mean serum NEP was significantly higher in women with preeclampsia compared to that of the gestational age-matched-controls (231.62 ± 65.30 pg/mL vs. 187.75 ± 84.38 pg/mL, p < 0.001). Mean serum NEP was significantly higher in the mild preeclampsia group compared to its gestational age-matched control group (228.84 ± 67.26 pg/mL vs. 186.14 ± 85.09 pg/mL, p = 0.008); and in the severe preeclampsia group compared to its gestational age-matched control group (234.45 ± 63.85 pg/mL vs. 189.29 ± 84.59 pg/mL, p = 0.004). Serum NEP was positively correlated with systolic and diastolic blood pressure, BUN, uric acid, and creatinine. CONCLUSION: Mean serum NEP was significantly higher in women with preeclampsia than women with an uncomplicated pregnancy. Further studies are needed to elucidate the possible therapeutic role of NEP inhibitors to treat preeclampsia.


Subject(s)
Neprilysin/blood , Pre-Eclampsia/diagnosis , Biomarkers/blood , Blood Pressure , Case-Control Studies , Female , Gestational Age , Humans , Pre-Eclampsia/blood , Pregnancy , Young Adult
8.
Adv Exp Med Biol ; 1330: 21-32, 2021.
Article in English | MEDLINE | ID: mdl-34339028

ABSTRACT

Epithelial ovarian cancer is a lethal gynecological cancer. It is related to high mortality because the majority of the patients present in advanced stage and because of the high recurrence rates of the disease. Recurrent ovarian cancer is classified according to the time interval between the last platinum-based chemotherapy and the occurrence of recurrence, to platinum-sensitive and platinum-resistant. Many theories tried to explain development of resistance to platinum-based therapy. "Cancer stem cells" is one of these theories and is being currently under investigation by many groups. This chapter will demonstrate the suggested contribution of cancer stem cells to the development of recurrent ovarian cancer.


Subject(s)
Neoplasms, Glandular and Epithelial , Ovarian Neoplasms , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Ovarian Epithelial/genetics , Drug Resistance, Neoplasm , Female , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplastic Stem Cells , Ovarian Neoplasms/drug therapy , Platinum
9.
Hypertens Pregnancy ; 40(2): 144-151, 2021 May.
Article in English | MEDLINE | ID: mdl-34014801

ABSTRACT

Objective: To evaluate the serum survivin level in preeclampsia.Methods: Eighty-eight pregnancies complicated with preeclampsia and 88 gestational-age (GA)-matched uncomplicated pregnancies were evaluated.Results: Mean serum survivin was detected to be significantly decreased in the early- (EOPE) and late-onset (LOPE) preeclampsia subgroups than the GA-matched control-groups; and were comparable in EOPE- and LOPE-groups after correction for GA. Serum survivin had weak negative correlations with systolic and diastolic arterial blood pressure.Conclusion: The serum survivin level was decreased in preeclamptic patients than the GA-matched controls. More comprehensive studies are needed to clarify the timing and extent of placental apoptosis in preeclampsia.


Subject(s)
Pre-Eclampsia/diagnosis , Survivin/blood , Adult , Biomarkers/blood , Case-Control Studies , Female , Gestational Age , Humans , Pre-Eclampsia/blood , Pregnancy
10.
J Matern Fetal Neonatal Med ; 34(8): 1249-1254, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31195859

ABSTRACT

AIM: To evaluate the possible associations between creatine kinase (CK), cardiac troponin T (cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), and s100B levels in umbilical cord blood and nonstress test results, cord-blood gas analyses and Apgar scores. MATERIAL AND METHODS: A total of 93 cesarean section deliveries after 34 + 0/7 gestational week (GW) were evaluated. The study (n = 50) and control (n = 43) groups consisted of type III and type I nonstress test (NST) according to the 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring. The serum levels of ProBNP II, S100-B, CK-MB, and cTnT were measured in cord blood and were evaluated according to the NST results, cord-blood gas analyses (pH and base-excess values) and 1- and 5-minute Apgar scores. Exclusion criteria for both groups included congenital abnormalities, multiple pregnancy, chorioamnionitis, oligohydramnios, polyhydramnios, intrauterine growth retardation (IUGR), and placental abruption. RESULTS: Mean age, weight, height, gestational age, and birth weight were comparable in type I and III NST groups. 1- and 5- minute Apgar, umbilical artery and vein pH values, and base deficiency were significantly lower in type III NST group compared to the type I NST group. The serum 100B (1616 ± 119 versus 533 ± 95 ng/L, p < .001), CK-MB (28.67 ± 21.17 versus 14.20 ± 11.26 ng/L, p < .001), cTnT (657 ± 396 versus 230 ± 132 ng/L, p < .001) and proBNP (1727 ± 379 versus 1069 ± 721 ng/L, p < .001) levels were significantly elevated in the NST type III compared to the NST type I group. The serum 100B, CK-MB, cTnT and proBNP levels were significantly elevated in the cord pH < 7.00 (n = 10) compared to pH = 7.00-7.15 group (n = 18). The serum 100B and proBNP were significantly elevated in the cord pH = 7.00-7.15 compared to the pH > 7.15 group (n = 65), whereas serum cTnT and proBNP levels were comparable in the latter two groups. In the study group, S100B, cTnT, and proBNP had negative correlations with 1- and 5-minute Apgar scores. All of the four markers showed negative correlations with A. umbilicalis pH and base excess. CONCLUSIONS: Mean S100B, CK-MB, cTnT, and NT-proBNP were significantly higher in the study group compared to the control group. The serum 100B, CK-MB, cTnT, and proBNP levels were significantly elevated in the cord pH < 7.00 compared to pH = 7.00-7.15 group. The serum 100B and proBNP were significantly elevated in the cord pH = 7.00-7.15 compared to the pH > 7.15 group.


Subject(s)
Natriuretic Peptide, Brain , Troponin T , Biomarkers , Cesarean Section , Child , Creatine Kinase , Female , Fetal Blood , Heart Rate, Fetal , Humans , Peptide Fragments , Placenta , Pregnancy , S100 Calcium Binding Protein beta Subunit
11.
J Obstet Gynaecol ; 41(6): 927-932, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33064040

ABSTRACT

Considering the complex pathogenesis of endometriosis, which is associated with many cellular or molecular processes, such as proliferation, angiogenesis, inflammation, we evaluated the diagnostic value of a quadruple panel of serum markers CA125, endocan, YKL-40 and copeptin, for the prediction of endometriosis and moderate - severe endometriosis. Seventy women with endometriosis and 70 women without endometriosis were evaluated. Serum CA125, endocan, copeptin and YKL-40 levels were significantly increased in women with endometriosis compared to the women without endometriosis and in the minimal - mild endometriosis group compared to the no-endometriosis group. YKL-40, endocan and copeptin levels were significantly increased in the moderate - severe endometriosis group compared to the mild -moderate endometriosis group but the difference in CA125 levels remained non-significant. The quadruple panel score had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis. Zero or one positive marker had a sensitivity of 91.4% and specificity of 88.57% to rule out endometriosis. In conclusion, a quadruple panel of serum markers-CA125, endocan, YKL-40, and copeptin may be beneficial for the diagnosis of endometriosis and especially moderate - severe endometriosis. Further studies are needed to prove the efficacy of this panel.Impact statementWhat is already known on this subject? Many serum markers including CA125 have been investigated so far and suggested to be associated with endometriosis. However, none of these markers is sensitive and specific enough to diagnose endometriosis.What do the results of this study add? A quadruple panel score (CA125, endocan, YKL-4 and copeptin) had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis.What are the implications of these findings for clinical practice and/or further research? A high score may be beneficial to warn the surgeon about the risk of moderate to severe endometriosis if the patient will be operated anyway. A negative test of the quadruple panel may show high odds that there is no endometriosis which may prevent unnecessary surgery.


Subject(s)
CA-125 Antigen/blood , Chitinase-3-Like Protein 1/blood , Endometriosis/diagnosis , Glycopeptides/blood , Hematologic Tests/statistics & numerical data , Membrane Proteins/blood , Neoplasm Proteins/blood , Proteoglycans/blood , Adolescent , Adult , Area Under Curve , Biological Specimen Banks , Biomarkers/blood , Female , Humans , Middle Aged , Predictive Value of Tests , Sensitivity and Specificity , Severity of Illness Index , Young Adult
12.
J Perinat Med ; 49(1): 60-66, 2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32866127

ABSTRACT

OBJECTIVES: To evaluate the serum levels of the serine proteinase inhibitor kallistatin in women with preeclampsia (PE). METHODS: The clinical and laboratory parameters of 55 consecutive women with early-onset PE (EOPE) and 55 consecutive women with late-onset PE (LOPE) were compared with 110 consecutive gestational age (GA)-matched (±1 week) pregnant women with an uncomplicated pregnancy and an appropriate for gestational age fetus. RESULTS: Mean serum kallistatin was significantly lower in women with PE compared to the GA-matched-controls (27.74±8.29 ng/mL vs. 37.86±20.64 ng/mL, p<0.001); in women with EOPE compared to that of women in the control group GA-matched for EOPE (24.85±6.65 ng/mL vs. 33.37±17.46 ng/mL, p=0.002); and in women with LOPE compared to that of women in the control group GA-matched for LOPE (30.87±8.81 ng/mL vs. 42.25±22.67 ng/mL, p=0.002). Mean serum kallistatin was significantly lower in women with EOPE compared to LOPE (24.85±6.65 ng/mL vs. 30.87±8.81 ng/mL, p<0.001). Serum kallistatin had negative correlations with systolic and diastolic blood pressure, creatinine, and positive correlation with GA at sampling and GA at birth. CONCLUSIONS: Serum kallistatin levels are decreased in preeclamptic pregnancies compared to the GA-matched-controls. This decrease was also significant in women with EOPE compared to LOPE. Serum kallistatin had negative correlation with systolic and diastolic blood pressure, creatinine and positive correlation with GA at sampling and GA at birth.


Subject(s)
Pre-Eclampsia/blood , Serpins/blood , Adult , Case-Control Studies , Female , Humans , Pregnancy , Young Adult
13.
J Obstet Gynaecol ; 40(1): 53-58, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31304822

ABSTRACT

The aim of this study was to examine a possible association between the levels of total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein(a), and the development of severe preeclampsia. We measured the levels of these lipoproteins in a prospective observational longitudinal cohort study that recruited 50 third-trimester pregnant women with mild preeclampsia at the time of recruitment. Two assessments were performed; the first measurement was at 29-31 weeks of pregnancy (at recruitment), and the second took place 4 weeks later. Patients with BMI 30, those < 20 years of age and those > 35 years of age were not included in the study. Eight mildly preeclamptic women developed severe preeclampsia within 4 weeks. In these patients, lipoprotein(a) level showed a twofold increase. A serum lipoprotein(a) level > 40.5 mg/dL in a mildly preeclamptic patient predicted the development of severe preeclampsia later on in the pregnancy, whereas a serum lipoprotein(a) level > 52.5 mg/dL was a marker of severity with high sensitivity and specificity. We suggest through our results that that lipoprotein(a) level correlates with the severity of the disease.IMPACT STATEMENTWhat is already known on this subject? Changes in blood lipids have been reported in preeclampsia. Abnormal lipoprotein levels are thought to play a role in the pathophysiology of the disease.What the results of this study add? In this study, we showed that a serum lipoprotein(a) level >40.5 mg/dL in a mildly preeclamptic patient predicted the development of severe preeclampsia later on in the pregnancy, whereas a serum lipoprotein(a) level >52.5 mg/dL was a marker of severity with high sensitivity and specificity.What the implications are of these findings for clinical practice and/or further research? Our results suggest that blood lipids, and especially lipoprotein(a), are involved in the pathogenesis of preeclampsia. The lipoprotein(a) level correlates with the severity of the disease. Hence, lipoprotein(a) could be used as a predictor of severe preeclampsia and a marker of the severity of preeclampsia. This should be validated through prospective studies recruiting an adequate sample size.


Subject(s)
Lipoprotein(a)/blood , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Pre-Eclampsia/blood , Severity of Illness Index , Adult , Female , Humans , Longitudinal Studies , Pregnancy , Pregnancy Trimester, Third/blood , Prospective Studies , Young Adult
14.
Int J Womens Health ; 11: 511-517, 2019.
Article in English | MEDLINE | ID: mdl-31572019

ABSTRACT

PURPOSE: To examine the effects of type of therapy (conservative therapy vs conization) on the psychosocial well-being of patients with cervical intraepithelial neoplasia grade II (CIN II) in a prospective cross-sectional study designed to simplify future choice of therapy. PATIENTS AND METHODS: In a cross-sectional study comparing 24 CIN II patients who were treated via conservative therapy with 17 CIN II patients who were treated via conization (not randomized), we examined the association between therapy type and psychosocial well-being after the treatment. Scores on the Hospital Anxiety and Depression Scale (HADS) (prevalence of depression/anxiety), SF-12 (health-related quality of life (HRQoL)) and Brief COPE (coping mechanisms) questionnaires were compared between the two subgroups via nonparametric Mann-Whitney U-tests. RESULTS: The prevalence of depression/anxiety and mental HRQoL did not differ between patients undergoing conservative therapy and those undergoing conization but differed significantly from those of the healthy population. Regarding physical HRQoL and coping strategies, the conservative therapy subgroup achieved higher scores and better performance. CONCLUSION: Patients with CIN II are at risk of developing depressive or anxiety symptoms. The choice of therapy seems to have an influence on physical HRQoL and coping strategies but not on depression/anxiety and mental HRQoL.

15.
J Turk Ger Gynecol Assoc ; 20(4): 247-254, 2019 11 28.
Article in English | MEDLINE | ID: mdl-30592193

ABSTRACT

Objective: To investigate the role of mammalian target of rapamycin (mTOR) in human granulosa cell ovarian tumors and the therapeutic effect of rapamycin in COV434 mitotic granulosa cell lines. Material and Methods: A retrospective evaluation of the medical records and pathologic sections of patients with granulosa cell ovarian carcinoma was performed. mTOR and p-mTOR expression was immunohistochemically investigated. A COV434 cell culture were treated with 0.5, 1, 2, and 5 µM rapamycin. Real-time growth curve analysis via xCELLigence system and apoptotic cell analysis via YO-PRO™-1 Iodide were performed to assess the therapeutic effect of rapamycin on cancer cells. Results: A total of twenty patients were evaluated. mTOR staining was detected in 18 (90%) patients. Mild, moderate, intense, and very intense staining was observed in three (15%), eight (40%), six (30%), and one (5%) sample, respectively. The mean mTOR staining ratio was 59±41%. P-mTOR staining was observed in two (10%) patients. One (5%) patient had 5% staining, and one (5%) patient had 100% staining for p-mTOR. Both of the latter patients had very intense staining. Rapamycin caused a dose-dependent growth arrest and induced apoptosis in COV434 mitotic granulosa cells. The real-time growth curves of the cells treated with these drugs were distinguished by a marked reduced slope after exposure for several hours, indicating a rapid onset of apoptosis. Live/dead cell analysis with YO-PRO-1 staining showed that rapamycin induced apoptosis in 24% of the cells when used at 1 µM concentration, whereas the rate increased to 61% and 72% when the cells were treated with 2 µM and 5 µM rapamycin, respectively. Conclusion: mTOR expression is observed in various degrees in 90%, and p-mTOR expression is observed in only 10% of patients with granulosa cell ovarian carcinoma. Rapamycin caused a dose-dependent growth arrest and apoptosis in COV434 mitotic granulosa cells.

16.
J Gynecol Oncol ; 29(4): e47, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29770618

ABSTRACT

OBJECTIVE: A numerical score, the peritoneal cancer index (PCI), was developed to reflect the extent of tumor growth in gastric and colorectal cancers and to tailor treatment. This study aimed to examine the value of the PCI score in advanced epithelial ovarian cancer (EOC) regarding completeness of surgical cytoreduction and survival. METHODS: This was a prospective observational cohort study. Patients with primary serous EOC at International Federation of Gynecology and Obstetrics (FIGO) stages IIIB or higher were included. Patients with FIGO stage IVB as well as those assigned to receive neoadjuvant treatment were excluded from the study. The PCI was obtained and registered intraoperatively. RESULTS: In the study period we recruited 96 patients with serous EOC stage IIIB-IVA. A PCI score cut-off value of 13 was calculated using a receiver operator characteristic (ROC) curve, above which worse survival is expected (area under the curve [AUC]=0.641; 95% confidence interval [CI]=0.517-0.765; sensitivity and specificity 80.6%, 45.0%, respectively; p=0.050). A multivariate analysis determined that suboptimal surgical cytoreduction was the only independent predictive factor for recurrence (odds ratio [OR]=7.548; 95% CI=1.473-38.675; p=0.015). A multivariate analysis determined that only suboptimal surgical cytoreduction (hazard ratio [HR]=2.33; 95% CI=0.616-8.795; p=0.005), but not PCI score >13 (HR=1.289; 95% CI=0.329-5.046; p=0.716), was an independent predictive factor for death. CONCLUSION: We conclude from this study that the PCI score is a reliable tool helping to assess the extent of disease in advanced serous EOC patients and may help predicting complete surgical cytoreduction but cannot qualify as a predictor of survival.


Subject(s)
Carcinoma, Ovarian Epithelial/mortality , Ovarian Neoplasms/mortality , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/secondary , Adult , Aged , Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/surgery , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Grading , Neoplasm Staging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , ROC Curve
17.
Infect Dis Obstet Gynecol ; 2017: 9350307, 2017.
Article in English | MEDLINE | ID: mdl-29104417

ABSTRACT

Objective: The risk factors for vulvar dysplasia and infections are not fully known. In this study, we aimed to investigate the correlation between pubic hair shaving and the occurrence of vulvar inflammation, dysplasia, and cancer. Methods: This study was performed between January 2013 and December 2016 in which a standardized questionnaire concerning genital hair shaving was administered to vulvar dysplasia and cancer patients and healthy participants. The presence of human papilloma virus (HPV) infection and the occurrence of genital inflammation were documented. Results: We recruited 49 patients with vulvar dysplasia or cancer and 234 healthy women as a control group. Smoking, HPV infection, genital inflammation, and complete pubic hair removal were significantly more common in the vulvar dysplasia/cancer group. Pubic hair shaving per se presented a clear association with vulvar dysplasia/cancer. Shaving the labia majora in particular showed also an association. Conclusion: Our findings suggest that partial or complete pubic hair shaving using a razor is correlated with and could be a potential risk factor for the development of genital inflammation, vulvar dysplasia, and malignancies. These results need to be confirmed in larger studies. HPV status and genital inflammation should be documented by medical personnel.


Subject(s)
Hair Removal/adverse effects , Inflammation/epidemiology , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Vulvar Neoplasms/epidemiology , Adult , Aged , Case-Control Studies , Female , Genitalia, Female/pathology , Genitalia, Female/virology , Humans , Inflammation/pathology , Inflammation/virology , Middle Aged , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Risk Factors , Surveys and Questionnaires , Vulvar Neoplasms/pathology , Vulvar Neoplasms/virology , Young Adult
18.
Int J Womens Health ; 9: 795-805, 2017.
Article in English | MEDLINE | ID: mdl-29133983

ABSTRACT

Our aim was to summarize the current relevant literature on concomitant psychiatric symptoms with a focus on anxiety/depression in a population with gynecologic cancer; to identify the predictors, associated factors, and prevention strategies of psychiatric disorders; to examine psychiatric disorders in a population with recurrent gynecologic cancer; and to describe the limitations of the literature and future research areas. Little is known about attending psychiatric disorders in patients with gynecologic and other malignant diseases like cervical or breast cancer. However, patients suffering from other types of gynecologic cancer (eg, genital/cervical cancer) may also have an increased risk of psychiatric symptoms. In this review, we identify the potential information deficits in this field. A two-rater independent literature search was conducted using the PubMed/Google Scholar search engines to systematically evaluate the literature on the research objectives, followed by a critical reflection on the results. Of the 77 screened studies, 15 met the criteria for inclusion in this review. Patients with gynecologic malignancies, especially cervical cancer, had a very high prevalence of psychiatric symptoms including depression (33%-52%). Additionally, the risk groups facing higher rates of concomitant reduced quality of life and increased psychiatric symptoms such as depression were identified. Specifically, low socioeconomic status, sexual inactivity, absence of a partner, and physical symptoms were correlated with an increased risk. Patients suffering from recurrent gynecologic cancer should receive particular attention because of their significantly increased risk of depressive symptoms. Screening programs are needed to detect psychiatric symptoms in cervical cancer patients and the associated high-risk groups. Regular screening should be implemented, and psychosocial care should be provided during follow-up.

19.
J Cancer Res Clin Oncol ; 142(5): 949-58, 2016 May.
Article in English | MEDLINE | ID: mdl-26762850

ABSTRACT

PURPOSE: Cluster of differentiation (CD) 44 is a cell surface receptor that correlates with the development of drug resistance in epithelial ovarian cancer (EOC). Here, we prospectively investigated the clinical impact of CD44 expression on the development of chemoresistance, and on disease-free and overall survival in EOC. METHODS: This study included patients with primary serous EOC that was at International Federation of Gynecology and Obstetrics stages IIIB-IVA and tumors that were CD44 positive and negative in a 1:1 ratio. All patients underwent primary surgical cytoreduction, followed by six cycles of combined paclitaxel and carboplatin chemotherapy every 3 weeks. The treatment was considered complete after the chemotherapy had finished. All patients were followed up for 24 months after completing their chemotherapy. RESULTS: Of the 96 patients with serous EOC at stages IIIB-IVA, 51 % of the tumors were negative for the expression of CD44 and 49 % showed variable CD44 expression. Patients who had CD44-positive tumors had statistically significant shorter disease-free (p ≤ 0.001) and overall survival (p ≤ 0.001) intervals compared with patients with CD44-negative tumors. The hazard ratio for death was 6.8 (95 % confidence interval 2.4-19.2, p ≤ 0.001) among the patients with CD44-positive tumors. A multivariate analysis showed that carboplatin-resistant or carboplatin-refractory EOC was the only independent predictive factor for death. CONCLUSIONS: CD44 expression contributes to the development of carboplatin resistance in advanced serous EOC, and it may contribute to worse prognoses for patients, but it is neither an independent predictor of survival nor of recurrence.


Subject(s)
Biomarkers, Tumor/metabolism , Cystadenocarcinoma, Serous/pathology , Drug Resistance, Neoplasm , Hyaluronan Receptors/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Adult , Aged , Antineoplastic Agents/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Ovarian Epithelial , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/mortality , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Neoplasms, Glandular and Epithelial/drug therapy , Neoplasms, Glandular and Epithelial/metabolism , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/mortality , Prognosis , Prospective Studies , Survival Rate
20.
Eur J Obstet Gynecol Reprod Biol ; 195: 83-87, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26479436

ABSTRACT

OBJECTIVES: To study the accuracy of four-dimensional (4D) ultrasound and power Doppler flow mapping in detecting tubal patency in women with sub-/infertility, and compare it with laparoscopy and chromopertubation. STUDY DESIGN: A prospective study. The study was performed in the outpatient clinic and infertility unit of a university hospital. The sonographic team and laparoscopic team were blinded to the results of each other. Women aged younger than 43 years seeking medical advice due to primary or secondary infertility and who planned to have a diagnostic laparoscopy performed, were recruited to the study after signing an informed consent. All of the recruited patients had power Doppler flow mapping and 4D hysterosalpingo-sonography by injecting sterile saline into the fallopian tubes 1 day before surgery. Registering Doppler signals, while using power Doppler, both at the tubal ostia and fimbrial end and the ability to demonstrate the course of the tube especially the isthmus and fimbrial end, while using 4D mode, was considered a patent tube. RESULTS: Out of 50 recruited patients, 33 women had bilateral patent tubes and five had unilateral patent tubes as shown by chromopertubation during diagnostic laparoscopy. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for two-dimensional power Doppler hysterosalpingography were 94.4%, 100%, 100%, 89.2%, and 96.2%, respectively and for 4D ultrasound were 70.4%, 100%, 100%, 70.4%, and 82.6%, respectively. CONCLUSIONS: Four-dimensional saline hysterosalpingography has acceptable accuracy in detecting tubal patency, but is surpassed by power Doppler saline hysterosalpingography. Power Doppler saline hysterosalpingography could be incorporated into the routine sub-/infertility workup.


Subject(s)
Fallopian Tube Diseases/diagnostic imaging , Fallopian Tubes/diagnostic imaging , Infertility, Female/diagnostic imaging , Ultrasonography, Doppler/methods , Adult , Cohort Studies , Fallopian Tube Diseases/diagnosis , Female , Humans , Hysterosalpingography , Infertility, Female/diagnosis , Laparoscopy/methods , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity
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