Nabil Abdalla

Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta

PurposeVarious studies in placental tissue suggest that diabetes mellitus alters the expression of glucose transporter (GLUT) proteins, with insulin therapy being a possible modulatory factor. The aim of the present study was quantitative evaluation of the expression of glucose transporters (GLUT-1, GLUT-4, GLUT-9) in the placenta of women in both, uncomplicated and diabetic pregnancy. Additionally, the effect of insulin therapy on the expression of selected glucose transporter isoforms was analyzed.MethodsTerm placental samples were obtained from healthy control (n = 25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n = 16), insulin-controlled gestational diabetes mellitus (GDMG2) (n = 6), and pre-gestational diabetes mellitus (PGDM) (n = 6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins.ResultsMorphometric analysis revealed a significant increase in the expression of GLUT-4 and GLUT-9 in insulin-dependent diabetic women (GDMG2 + PGDM) as compared to both, control and GDMG1 groups (p < .05). Significantly increased GLUT-1 expression was observed only in placental specimens from patients with PGDM (p < .05). No statistically significant differences in GLUT expression were found between GDMG1 patients and healthy controls.ConclusionsThe results of the study confirmed the presence of GLUT-1, GLUT-4 and GLUT-9 proteins in the trophoblast from both, uncomplicated and diabetic pregnancies. In addition, insulin therapy may increase placental expression of GLUT-4 and GLUT-9, and partially GLUT-1, in women with GDMG2/PGDM.

Placental tumor (chorioangioma) as a cause of polyhydramnios: a case report

Placental chorioangioma is the most common type of placental tumor. It is usually symptomless and may be associated with serious maternal and fetal complication when it reaches a large size. We presented a case of an angiomatous type of placental hemangioma diagnosed in the second trimester of pregnancy in a patient with polyhydramnios. A normal volume of amniotic fluid was successfully achieved by three amnioreductions with conservative management. The size of the placental tumor remained the same from the time of diagnosis to the end of pregnancy. A term labor was uncomplicated and a healthy newborn was delivered. Macroscopic and microscopic examination of the placenta confirmed the diagnosis. Despite the rarity of placental tumors, they should be considered as differential diagnosis in cases of polyhydramnios.

P08.12: Doppler assessment of fetoplacental velocimetry in pregnancies complicated by insulin dependent diabetes mellitus

Objectives: The objective of this study was to determine if Doppler changes in fetuses with normal growth could identify pregnancies at risk for fetal death. Methods: A case-control study was performed on patients enrolled in a longitudinal study who had an ultrasound evaluation approximately every 4 weeks prior to delivery or fetal death. Cases included patients who had a fetal death (n = 14) of a fetus with normal growth. Controls consisted of women who delivered an appropriately grown neonate at term (n = 28). Cases were matched to controls (1:2) by gestational age at the time of ultrasound evaluation (±2 weeks), race, maternal age, tobacco use, BMI and maternal medical conditions (e.g. chronic hypertension, pre-eclampsia, gestational hypertension, gestational diabetes, and pre-gestational diabetes). Doppler evaluation of the fetal middle cerebral (MCA), umbilical (UA), and uterine arteries (UtA) were performed and vascular ratios (MCA/UA and MCA/UtA) were calculated. Values above the 95th centile or below the 5th centile were considered abnormal. Conditional logistic regression was used to determine whether Doppler parameters were significantly associated with fetal demise. Significantly associated parameters were dichotomized to illustrate associations. Results: The median gestational age at the diagnosis of fetal death was 29 6/7 weeks (range: 21–38 2/7 weeks). The median time interval between ultrasound to diagnosis was 7 weeks (range: 6–11 weeks) for cases and 16 weeks for controls (range: 14–19 weeks). One case of fetal death was diagnosed prior to 24 weeks and two cases at term (> 37 weeks). The MCA/UtA ratio was significantly associated with fetal demise (OR 0.23; CI 0.06–0.94). Conclusions: In appropriately grown fetuses, MCA/UtA ratio is significantly associated with fetal demise.

The role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies

OBJECTIVES The aim of the study was to assess the role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies. MATERIAL AND METHODS A retrospective study of 87 patients with endometrial pathologies was conducted. Tumor markers were assessed two weeks before surgical intervention in each subject. The final diagnosis was established on the basis of the histopathological examination of the endometrium. RESULTS Serum HE4 levels were significantly higher in patients with endometrial cancer (EC) as compared to non-malignant endometrial pathologies (p < 0.001), patients with stage I EC as compared to non-malignant endometrial pathologies (p < 0.001), and patients with stage Ia EC as compared to non-malignant endometrial pathologies (p = 0.003). Serum CA125 levels were not significantly different as far as these groups of patients were concerned. Both tumor markers were significantly higher in patients with stage II-III as compared to stage I EC and non-malignant endometrial pathologies (p < 0.001 for both markers). Sensitivity and specificity of HE4 at the cut-off level of 70 pmol/L for detecting endometrial malignancies were 73.08% and 85.71%, respectively. Sensitivity and specificity of CA125 at the cut-off level of 35 U/mL were 29.41% and 94.29%, respectively. The area under the curve (AUC) for HE4 was 0.875, suggesting that this marker reliably differentiates malignant from non-malignant endometrial pathologies (p < 0.001). AUC for CA125 was 0.552, suggesting that this marker does not reliably differentiate between malignant and non-malignant endometrial pathologies (p = 0.414). CONCLUSION HE4, in contrast to CA125, might be a useful tool for detecting malignant endometrial pathologies.

Clinical, ultrasound parameters and tumor marker-based mathematical models and scoring systems in pre-surgical diagnosis of adnexal tumors

The choice of management for patients with adnexal tumors requires careful pre-surgical assessment. In case of adnexal masses, the diagnostic difficulties arise from the heterogenic nature of the adnexal diseases, presence of multiple functional changes, and lack of early symptoms of malignancy. A reliable pre-surgical differentiation cannot be performed using clinical features, ultrasound examination, or tumor markers alone. New diagnostic techniques and novel markers are under investigations, however no single test can be used to conclusively differentiate between malignant and non-malignant adnexal masses. Mathematical models and scoring systems based on different clinical, ultrasonographic and laboratory parameters alone or together may facilitate the diagnosis. Selected mathematical models and scoring systems are presented in this article. Models using only ultrasound features include simple rules, regression models, Gynecologic Imaging Report and Data System, and various morphologic scores. Some logistic regression models are based on multiple clinical and ultrasound data. The OVA1 test is based on five tumor markers without using other data. The Risk of Malignancy Algorithm uses two tumor markers with one clinical parameter. i.e. the menopausal status. Some models used clinical, ultrasound and tumor marker data together. This group of models includes risk of malignancy indices, artificial neural networks, and the ADNEX model. Although some of these models have been compared in the literature, more prospective studies are needed to select the most effective model, to develop the existing models, or to create new more effective models of oncological assessment of the adnexal tumors.

Presurgical diagnostic difficulties in an asymptomatic patient with primary transitional cell carcinoma of the oviduct: case report

Primary transitional cell carcinoma of the fallopian tube is a very rare condition. We present a case of a 70-year-old asymptomatic Caucasian patient with an irregular solid right adnexal mass of 67 × 35 × 59 mm which was discovered during routine ultrasound pelvic examination. There was no acoustic shadow and the patient did not feel pain during examination. No evidence of metastases or ascites was found by ultrasound. There was moderate vascularization of the mass. The mass was considered malignant according to the subjective assessment of the examiner. Serum level of CA125 was elevated to 519 U/ml. The results of logistic regression model LR2 according to the International Ovarian Tumor Analysis (IOTA) group was 64.4%, suggesting the malignant nature of the mass. The IOTA-ADNEX model showed 97% probability of malignancy, probably (85.5%) stage II-IV ovarian cancer. The risk of malignancy being borderline, stage I and metastatic was 0.6%, 3.9% and 7%, respectively. Omitting CA125 in the IOTA-ADNEX model slightly decreased the probability of malignancy to 81.3%, still most likely (54.2%) stage II-IV ovarian cancer. The results of risk of malignancy indices RMI I-IV were 1557, 2076, 1557 and 2076, respectively, reflecting the malignant nature of the mass. The final diagnosis was transitional cell carcinoma of the fallopian tube, stage IIIc according to FIGO.

Does the Risk of Ovarian Malignancy Algorithm Provide Better Diagnostic Performance Than HE4 and CA125 in the Presurgical Differentiation of Adnexal Tumors in Polish Women

Aim This study compared the diagnostic performance of the Risk of Ovarian Malignancy Algorithm (ROMA) and HE4 and CA125 for the presurgical differentiation of adnexal tumors. Material and Methods This prospective study included 302 patients admitted for surgical treatment due to adnexal tumors. The ROMA was calculated depending on CA125, HE4, and menopausal status. Results Fifty patients were diagnosed with malignant disease. In the differentiation of malignant from nonmalignant adnexal tumors, the area under curve (AUC) was higher for ROMA and HE4 than that for CA125 in both the premenopausal and postmenopausal subgroups. In the differentiation of stage I FIGO malignancies and epithelial ovarian cancer from nonmalignant pathologies, the AUC of HE4 and ROMA was higher than that of CA125. The ROMA performed significantly better than CA125 in the differentiation of all malignancies and differentiation of stage I FIGO malignancies from nonmalignant pathologies (p = 0.043 and p = 0.025, resp.). There were no significant differences between the ROMA and the tumor markers for any other variants. Conclusions The ROMA is more useful than CA125 for the differentiation of malignant (including stage I FIGO) from nonmalignant adnexal tumors. It is also as useful as HE4 and CA125 for the differentiation of epithelial ovarian cancer from nonmalignant adnexal tumors.

Can ultrasound be helpful in selecting optimal management methods for pregnancies complicated by placental non-trophpblastic tumors?

Placental chorioangioma is the most common subtype of non-trophoblastic placental tumors. Other subtypes are very rare and usually associated with an uneventful course of pregnancy. Most chorioangiomas are small and of no clinical significance. Giant chorioangiomas may be associated with serious fetal and maternal complications. So far, no established ultrasound guidelines are available for the management of placental non-trophoblastic tumors. This may be attributed to the rarity of the disease entity and its different clinical features and complications. In this article, the role of ultrasound findings such as the tumor’s size, vascularity, feeding vessels, amniotic fluid and location of the placenta in the diagnosis, treatment and follow up of these tumors is presented relying on up-todate literature review. Conservative management with serial ultrasound examinations can be an adequate method for monitoring small uncomplicated tumors. Ultrasound-guided procedures such as amnioreduction and cordocentesis can be used for amelioration of complications. Chorioangioma-specific treatment is reserved for complicated cases in the second trimester of pregnancy when prematurity is a matter of concern. Endoscopic laser ablation is indicated when the feeding vessel is superficial and small. Interstitial laser ablation is helpful when the placenta is located in the anterior uterine wall. Ligation of the feeding vessels is preferred when they are large. Alcohol injection should be performed away from the vasculature to prevent toxicity. Microcoils should be inserted as near as possible to the tumor to prevent collateral formation. Ultrasound is also a method of choice for monitoring the effectiveness of these procedures.

Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus

Abstract Purpose: The aim of the study was to analyze the correlations between the expression of glucose transporters GLUT-1, GLUT-4, and GLUT-9 in human term placenta and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus (DM). Materials and methods: Placental samples were obtained from healthy control (n = 25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n = 16), insulin-controlled gestational diabetes mellitus (GDMG2) (n = 6), and pregestational DM (PGDM) (n = 6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins. For the purposes of correlation analysis, the following parameters were selected: type of diabetes, gestational age, maternal prepregnancy body mass index (BMI), gestational weight gain, third trimester glycated hemoglobin concentration, placental weight, fetal birth weight (FBW) as well as ultrasonographic indicators of fetal adiposity, including subscapular (SSFM), abdominal (AFM), and midthigh (MTFM) fat mass measurements. Results: In the PGDM group, the analysis demonstrated positive correlations between the placental expression of GLUT-1, GLUT-4, and GLUT-9 and FBW, AFM, and SSFM measurements (p < .05). Similarly in the GDMG2 patients positive correlations between GLUT-4 expression, FBW and SSFM were observed (p < .05). In the multivariate regression analysis, only the type of diabetes and FBW were significantly associated with GLUTs expression (p < .001). In addition, maternal prepregnancy BMI significantly contributed to GLUT-1 expression (p < .001). Conclusions: The study results revealed that placental expression of GLUT-1, GLUT-4, and GLUT-9 may be involved in the intensification of the fetal growth in pregnancies complicated by GDM/PGDM.

Can Replacing CA125 with HE4 in Risk of Malignancy Indices 1–4 Improve Diagnostic Performance in the Presurgical Assessment of Adnexal Tumors?

Aims To assess whether replacing CA125 with HE4 in the classical formulas of risk of malignancy indices (RMIs) can improve diagnostic performance. Methods For each of 312 patients with an adnexal mass, classical RMIs 1–4 were computed based on ultrasound score, menopausal status, and serum CA125 levels. Additionally, modified RMIs (mRMIs) 1–4 were recalculated by replacing CA125 with HE4. Results Malignant pathology was diagnosed in 52 patients (16.67%). There was no significant difference in diagnostic performance (area under the receiver operating characteristic curve [AUC]) between each classical RMI and its corresponding mRMI. In the entire sample, the AUC was 0.899, 0.900, 0.895, and 0.908 for classical RMIs 1–4 compared to 0.903, 0.929, 0.930, and 0.931 for mRMIs 1–4. In premenopausal patients, the AUC was 0.818, 0.798, 0.795, and 0.802 for classical RMIs 1–4 compared to 0.839, 0.875, 0.876, and 0.856 for mRMIs 1–4. In postmenopausal patients, the AUC was 0.906, 0.895, 0.896, and 0.906 for classical RMIs 1–4 compared to 0.907, 0.923, 0.924, and 0.930 for mRMI 1–4. Conclusions Use of HE4 instead of CA125 did not significantly improve diagnostic performance of RMIs 1–4 in patients with an adnexal mass.