Factors contributing to variability in metformin concentration in polycystic ovary syndrome.

AIM: To investigate the factors affecting metformin concentrations after chronic administration in patients with polycystic ovary syndrome (PCOS), focusing on the pharmacokinetic variability and its implications for personalized therapy. METHODS: This study enrolled 53 PCOS patients undergoing long-term metformin treatment at the Clinic for Gynecology and Obstetrics in Nis, Serbia, from February to December 2019. Pharmacokinetic parameters were measured from blood samples, and metformin concentrations were determined with validated analytical techniques. RESULTS: There was a significant variability in metformin concentrations among PCOS patients, with body mass index (BMI) identified as a major influencing factor. Higher BMI was associated with lower plasma metformin levels, a finding suggesting an altered pharmacokinetic profile in obese patients. CONCLUSIONS: This study highlights the critical role of BMI in influencing metformin pharmacokinetics in PCOS patients and underscores the need for personalized treatment strategies in patients with PCOS.

Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant.

Multiple sclerosis (MS), a noncurable autoimmune neurodegenerative disease, requires constant research that could improve understanding of both environmental and genetic factors that lead to its occurrence and/or progression. Recognition of the genetic basis of MS further leads to an investigation of the regulatory role of genetic variants on gene expression. Among risk variants for MS, Ikaros zinc finger 3 (IKZF3) gene variant rs12946510 was identified as one of the top-ranked and the expression quantitative trait loci (eQTL) for genes residing in chromosomal locus 17q12-21. The study aimed to investigate the association of gene expression of the immunologically relevant genes, which map to indicated locus, ORMDL3, GSDMB, and IKZF3, with MS and rs12946510 genotype, taking into account disease phase, clinical parameters of disease progression, and severity and immunomodulatory therapy. We used TaqMan® technology for both allelic discrimination and gene expression determination in 67 relapsing MS patients and 50 healthy controls. Decreased ORMDL3 and GSDMB mRNA levels had significant associations with MS and rs12946510 TT rare homozygote among patients. Significant positive correlations between ORMDL3 and GSDMB mRNA expression were observed in both patients and controls. We detected the significant between-effect of sex and rs12946510 on the expression of ORMDL3 in the patient group and interferon ß therapy and rs12946510 on GSDMB expression. Our results show the association of ORMDL3 and GSDMB mRNA expression with the clinical manifestation of MS and confirm that IKZF3 rs12946510 exerts the eQTL effect on both genes in multiple sclerosis. Besides providing novel insight related to MS phases and interferon ß therapy, the study results confirm previous studies on regulatory genetic variants, autoimmunity, and MS.

Monte Carlo Optimization Method Based QSAR Modeling of Placental Barrier Permeability.

PURPOSE: In order to ensure that drug administration is safe during pregnancy, it is crucial to have the possibility to predict the placental permeability of drugs in humans. The experimental method which is most widely used for the said purpose is in vitro human placental perfusion, though the approach is highly expensive and time consuming. Quantitative structure-activity relationship (QSAR) modeling represents a powerful tool for the assessment of the drug placental transfer, and can be successfully employed to be an alternative in in vitro experiments. METHODS: The conformation-independent QSAR models covered in the present study were developed through the use of the SMILES notation descriptors and local molecular graph invariants. What is more, the Monte Carlo optimization method, was used in the test sets and the training sets as the model developer with three independent molecular splits. RESULTS: A range of different statistical parameters was used to validate the developed QSAR model, including the standard error of estimation, mean absolute error, root-mean-square error (RMSE), correlation coefficient, cross-validated correlation coefficient, Fisher ratio, MAE-based metrics and the correlation ideality index. Once the mentioned statistical methods were employed, an excellent predictive potential and robustness of the developed QSAR model was demonstrated. In addition, the molecular fragments, which are derived from the SMILES notation descriptors accounting for the decrease or increase in the investigated activity, were revealed. CONCLUSION: The presented QSAR modeling can be an invaluable tool for the high-throughput screening of the placental permeability of drugs.

A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.

Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.

Maternal plasma proteome profiling of biomarkers and pathogenic mechanisms of early-onset and late-onset preeclampsia.

Preeclampsia is still the leading cause of morbidity and mortality in pregnancy without a cure. There are two phenotypes of preeclampsia, early-onset (EOPE) and late-onset (LOPE) with poorly defined pathogenic differences. This study aimed to facilitate better understanding of the mechanisms of pathophysiology of EOPE and LOPE, and identify specific biomarkers or therapeutic targets. In this study, we conducted an untargeted, label-free quantitative proteomic analyses of plasma samples from pregnant women with EOPE (n = 17) and LOPE (n = 11), and age, BMI-matched normotensive controls (n = 18). Targeted proteomics approach was also employed to validate a subset of proteins (n = 17). In total, there were 26 and 20 differentially abundant proteins between EOPE or LOPE, and normotensive controls, respectively. A series of angiogenic and inflammatory proteins, including insulin-like growth factor-binding protein 4 (IGFBP4; EOPE: FDR = 0.0030 and LOPE: FDR = 0.00396) and inter-alpha-trypsin inhibitor heavy chain H2-4 (ITIH2-4), were significantly altered in abundance in both phenotypes. Through validation we confirmed that ITIH2 was perturbed only in LOPE (p = 0.005) whereas ITIH3 and ITIH4 were perturbed in both phenotypes (p < 0.05). Overall, lipid metabolism/transport proteins associated with atherosclerosis were highly abundant in LOPE, however, ECM proteins had a more pronounced role in EOPE. The complement cascade and binding and uptake of ligands by scavenger receptors, pathways, were associated with both EOPE and LOPE.

Quality Control in the Slovenian National Colorectal Cancer Screening Program.

OBJECTIVES: The objective of the study was to assess the impact of an internal quality indicator (QI) audit on the quality level of colonoscopies in the National Colorectal Cancer Screening Program (NCCSP). DESIGN: Sixty-eight colonoscopists from 29 endoscopic centres participated in the NCCSP from April 2009 to January 2015. Controlled QIs were the percentage of total colonoscopies, adenoma detection rate (ADR), mean adenoma per procedure (MAP), mean adenoma per positive procedure (MAP+), right-sided ADR, sessile serrated lesion (SSL) detection rate, and patient responses to post-procedural questionnaires. A group of 3 expert endoscopists from the NCCSP Council performed 91 inspections and provided education. RESULTS: A total of 891.364 (58.2%) Slovenian citizens participated in the first 3 screening rounds of the NCCSP. Among 46.552 (6%) positive individuals, 42.866 (92.1%) underwent first colonoscopies. Total colonoscopies were performed in 98% of endoscopies (p = 0.459 between cycles), mean ADR was 51.8% (p = 0.872 between cycles), mean percentage of adenoma in the right colon was 37.5% (p = 0.227 between cycles), mean MAP was 1.1 (p = 0.981 between cycles), mean MAP+ was 2.0 (p = 0.824 between cycles), and mean SSL detection rate was 3% (p < 0.001). We observed great difference in QIs between endoscopists and a significant increase in MAP, ADR in the right colon, and SSL per endoscopist during the 6-year period. Due to quality underperformance, 3 endoscopic centres (10.3%) and 13 endoscopists (19.1%) were excluded from the program. CONCLUSIONS: The success of the NCCSP is related to the quality of colonoscopies performed. To ensure the proper quality level, regular audit and permanent education are needed.

Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia.

BACKGROUND: Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. METHODS: The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion. Immunofluorescent staining was also conducted to analyse the expression of cardiac FKBPL. Cardiac spheroids were generated using human cardiac fibroblasts and human coronary artery endothelial cells and treated with patient plasma from normotensive controls, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE); n = 3. FKBPL and CD31 expression was quantified by immunofluorescent labelling. RESULTS: The RUPP procedure induced significant increases in blood pressure (p < 0.001), collagen deposition (p < 0.001) and cardiac BNP45 (p < 0.05). It also induced a significant increase in cardiac FKBPL mRNA (p < 0.05) and protein  expression  (p < 0.01). RUPP placentae also exhibited increased collagen deposition and decreased Flt1 mRNA expression (p < 0.05). RUPP kidneys revealed an increase in average glomerular size (p < 0.05). Cardiac spheroids showed a significant increase in FKBPL expression when treated with LOPE plasma (p < 0.05) and a trend towards increased FKBPL expression following treatment with EOPE plasma (p = 0.06). CONCLUSIONS: The rat RUPP model induced cardiac, renal and placental features reflective of preeclampsia. FKBPL was increased in the hearts of RUPP rats and cardiac spheroids treated with plasma from women with preeclampsia, perhaps reflective of restricted angiogenesis and inflammation in this disorder. Elucidation of these novel FKBPL mechanisms in cardiac health in preeclampsia could be key in preventing future CVD.

Predictors of poor neonatal outcomes in fetuses diagnosed with congenital urinary tract anomalie.

OBJECTIVES: Urinary tract anomalies account for approximately one-quarter of all antenatally detected anomalies. The aim of this study was to identify factors associated with severe adverse neonatal outcomes of a prenatally diagnosed urinary tract anomaly. MATERIAL AND METHODS: A retrospective-prospective study included 101 pregnant women with prenatally diagnosed fetal urinary tract anomalies presented to the Council for Fetal Anomalies. Prenatal diagnoses were compared with autopsy findings in cases of terminated pregnancy or with clinical and operative findings of the infants. RESULTS: The mortality rate in the group of patients with fetal obstructive uropathy (60 patients) was 10% and in the group of patients with fetal multicystic dysplastic kidney (38 patients) 15.7%. Surgery was performed on 53.4% of the children, whereas more than half of the operations involved resolving associated urinary tract anomalies. Postoperative renal function deterioration occurred in 19% of the children. CONCLUSIONS: The prognosis of renal function in obstructive uropathies is excellent if oligoamnios does not develop prenatally and in case of timely provided surgical care is provided postnatally. The finding of the bilateral multicystic dysplastic kidney is associated with poor prognosis. The prognosis in fetal unilateral multicystic dysplastic kidney depends primarily on the condition of the contralateral kidney and the existence of associated anomalies.

Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis.

BACKGROUND: Leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1A) are involved in the pathogenesis of multiple sclerosis (MS) by affecting the inflammatory response and reactive oxygen species production. LEP rs7799039 and LEPR rs1137101 genetic variants modify the serum LEP levels and PGC1A rs8192678 alters the PGC1A activity. The study objective was to explore the associations of these variants with susceptibility to MS, disease course/clinical parameters and also with peripheral blood mononuclear cell expression of the target genes and plasma LEP concentrations, in the study subjects. METHODS: The study groups included 528 patients with MS and 429 controls. TaqMan® assays were used for genotyping and gene expression quantification. The Chi-square, parametric and nonparametric tests and simple/multiple logistic regression were performed for the statistical analysis of data. RESULTS: A multiple logistic regression model including all three investigated variants, applied to patients (RRMS + SPMS) and controls, showed that PGC1A rs8192678 minor allele had an increased risk for the occurrence of disease, with OR (95%CI) = 1,32 (1,01-1,73), P = 0,04. Between-effect of gender and LEPR variant on the multiple sclerosis severity score (MSSS) was identified (P = 0,005). In male patients (relapsing-remitting and secondary progressive), LEPR minor allele carriers had increased MSSS (GG + AG vs AA, median (minimum-maximum) = 5,38 (0,64-9,88) vs 4,27 (0,78-9,63); P = 0,01, Padj = 0,03). In relapsing-remitting patients LEP rs7799039 affected the LEP gene expression (P = 0,006; Padj = 0,04). CONCLUSION: The current findings implicate an impact of investigated genetic variants on the pathogenesis of MS.

Optical diagnosis of colorectal polyp images using a newly developed computer-aided diagnosis system (CADx) compared with intuitive optical diagnosis.

BACKGROUND: Optical diagnosis of colorectal polyps remains challenging. Image-enhancement techniques such as narrow-band imaging and blue-light imaging (BLI) can improve optical diagnosis. We developed and prospectively validated a computer-aided diagnosis system (CADx) using high-definition white-light (HDWL) and BLI images, and compared the system with the optical diagnosis of expert and novice endoscopists. METHODS: CADx characterized colorectal polyps by exploiting artificial neural networks. Six experts and 13 novices optically diagnosed 60 colorectal polyps based on intuition. After 4 weeks, the same set of images was permuted and optically diagnosed using the BLI Adenoma Serrated International Classification (BASIC). RESULTS: CADx had a diagnostic accuracy of 88.3 % using HDWL images and 86.7 % using BLI images. The overall diagnostic accuracy combining HDWL and BLI (multimodal imaging) was 95.0 %, which was significantly higher than that of experts (81.7 %, P = 0.03) and novices (66.7 %, P < 0.001). Sensitivity was also higher for CADx (95.6 % vs. 61.1 % and 55.4 %), whereas specificity was higher for experts compared with CADx and novices (95.6 % vs. 93.3 % and 93.2 %). For endoscopists, diagnostic accuracy did not increase when using BASIC, either for experts (intuition 79.5 % vs. BASIC 81.7 %, P = 0.14) or for novices (intuition 66.7 % vs. BASIC 66.5 %, P = 0.95). CONCLUSION: CADx had a significantly higher diagnostic accuracy than experts and novices for the optical diagnosis of colorectal polyps. Multimodal imaging, incorporating both HDWL and BLI, improved the diagnostic accuracy of CADx. BASIC did not increase the diagnostic accuracy of endoscopists compared with intuitive optical diagnosis.

The impact of 6 years of the National Colorectal Cancer Screening Program on colorectal cancer incidence and 5-year survival.

We aimed to assess the impact of the first three rounds of the National Colorectal Cancer Screening Program (NCCSP) on CRC incidence and mortality in Slovenia. In NCCSP, we use two fecal immune tests (FITs) and if test is positive patient is referred to colonoscopy. From 2009, we invite Slovenian residents aged 50-69 years, one screening round takes 2 years. The response rate was from 56.9 to 59.9%. FIT was positive in 6.0-6.2% (more in older patients and in men; P < 0.05). The adenoma detection rate was >51.3% (more in men; P < 0.01). In NCCSP, 70.3% of all cancers diagnosed were in stages I and II, while 20.7% of all CRC were found in polyps resected during colonoscopies. Patients with positive first FIT have odds ratio 2.19 [95% confidence interval (CI), 2.06-2.32] for advanced neoplasia and cancer compared to patients with two negative FITs. The incidence rate for CRC has dropped significantly after 6 years in population and in men (P < 0.01) but not in women. Five-year CRC survival was 31.3% higher if cancer was diagnosed in NCCSP (P < 0.05). After 6 years of NCCSP, the incidence rate for CRC has dropped significantly (P < 0.01). Hazard ratio for death from CRC was 3.84 higher (95% CI, 3.36-4.40; P < 0.001) in patients with cancer detected outside the program.

Cesarean Scar Pregnancy Successfully Managed to Term: When the Patient Is Determined to Keep the Pregnancy.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy, defined as the implantation of the gestational sac at the uterine incision scar of the previous cesarean section. This condition is associated with severe maternal and fetal/neonatal complications, including severe bleeding, rupture of the uterus, fetal demise, or preterm delivery. In view of these, early diagnosis allows the option of termination of pregnancy. In this case report, we present a patient with a cesarean scar pregnancy who was diagnosed at the sixth week of gestation but declined early termination of the pregnancy and was managed to the 38th week. Placenta previa was confirmed in the second trimester. A planned cesarean section was performed that resulted in the birth of a live full-term neonate. Intraoperatively, placenta percreta was diagnosed, and due to uncontrollable bleeding, a hysterectomy was performed. The postoperative course was uneventful. In cases where an early diagnosis of CSP is made, women should be counseled that this will almost certainly evolve to placenta previa, and the associated risks should be explained. Close follow-up of CSP is mandatory if expectant management is selected. Further studies are needed for definitive conclusions and to determine the risks of expectant management.

The association of genetic variants IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510 with multiple sclerosis onset and severity in patients from Serbia.

An algorithm Probabilistic Identification of Causal SNPs, identified 434 causal variants for multiple sclerosis (MS) including IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510. Analysis of individual and combined effects of these variants in the Serbian population identified that Il2RA rs2104286 G allele carriers had a lower risk for developing MS (gender adjusted OR = 0.63, p = .003). With regard to the IFI30 rs11554159 recessive genetic model, among HLA-DRB1*15:01 positive patients, the AA homozygote had a significantly higher MSSS compared to the G allele carriers (p = .003). This study confirms role of IL2RA rs2104286 in MS and suggest the role of IFI30 rs11554159 in disease severity, which needs validation.

Development and validation of the international Blue Light Imaging for Barrett's Neoplasia Classification.

BACKGROUND AND AIMS: Detecting subtle Barrett's neoplasia during surveillance endoscopy can be challenging. Blue-light imaging (BLI) is a novel advanced endoscopic technology with high-intensity contrast imaging that may improve the identification of Barrett's neoplasia. The aim of this study was to develop and validate the first classification to enable characterization of neoplastic and non-neoplastic Barrett's esophagus using BLI. METHODS: In phase 1, descriptors pertaining to neoplastic and non-neoplastic Barrett's esophagus were identified to form the classification, named the Blue Light Imaging for Barrett's Neoplasia Classification (BLINC). Phase 2 involved validation of these component criteria by 10 expert endoscopists assessing 50 BLI images. In phase 3, a web-based training module was developed to enable 15 general (nonexpert) endoscopists to use BLINC. They then validated the classification with an image assessment exercise in phase 4, and their pre- and post-training results were compared. RESULTS: In phase 1 the descriptors were grouped into color, pit, and vessel pattern categories to form the classification. In phase 2 the sensitivity of neoplasia identification was 96.0% with a very good level of agreement among the experts (κ = .83). In phase 3, 15 general endoscopists completed the training module. In phase 4 their pretraining sensitivity (85.3%) improved significantly to 95.7% post-training with a good level of agreement (κ = .67). CONCLUSIONS: We developed and validated a new classification system (BLINC) for the optical diagnosis of Barrett's neoplasia using BLI. Despite the limitations of this image-based study with a high prevalence of neoplasia, we believe it has the potential to improve the optical diagnosis of Barrett's neoplasia given the high degree of sensitivity (96%) noted. It is also a promising tool for training in Barrett's esophagus optical diagnosis using BLI.

Optical diagnosis of colorectal polyps with Blue Light Imaging using a new international classification.

Background: Blue Light Imaging (BLI) is a new imaging technology that enhances mucosal surface and vessel patterns. A specific BLI classification was recently developed to enable better characterisation of colorectal polyps (BLI Adenoma Serrated International Classification (BASIC)). The aim of this study was to validate the diagnostic performance of BASIC in predicting polyp histology in experienced and trainee endoscopists. Methods: Five experienced and five trainee endoscopists evaluated high-definition white light (HDWL) and BLI images from 45 small polyps to assess baseline accuracy, sensitivity, specificity, and positive and negative predictive values (NPVs) of polyp histology. Each endoscopist was trained with the BLI classification before repeating the exercise. Results were compared pre- and post-training. Results: The overall pre-training accuracy improved from 87% to 94%. The sensitivity and NPV of adenoma diagnosis also improved significantly from 79% to 96% and 81% to 95% with BASIC training. This improvement was noted in both groups. The interobserver level of agreement was very good (K = 0.90) in the experienced cohort and good (K = 0.66) in the trainee group post-training. Conclusions: BLI is a useful tool for optical diagnosis, and the use of BASIC with adequate training can significantly improve the accuracy, sensitivity and NPV of adenoma diagnosis.

T lymphocytes in the third trimester decidua in preeclampsia.

OBJECTIVE: The aim of study was to conduct immunohistochemical quantification of CD3+ and CD8+ decidual lymphocytes in preeclampsia. METHODS: A study group included 30 cases of preeclampsia and a control group included 20 healthy pregnant women, all delivered by Cesarean section. Samples of placental bed were analyzed after immunohistochemical staining of CD45+, CD3+ and CD8+ cells. RESULTS: The group with preeclampsia included a significantly higher number of CD3+ (p < 0.01) and CD8+ (p < 0.05) T lymphocytes. CONCLUSION: It is certain that thebalance dysregulation of T cell of the immune milieu of deciduais of importance in etiopathogenesis and manifestations of preeclampsia.

Results of the FIT-based National Colorectal Cancer Screening Program in Slovenia.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies in the western world. OBJECTIVE: We aimed to assess the first round of fecal immunochemical test (FIT)-based National CRC screening program (NCSP). METHODS: In the NCSP conducted in Slovenia, a FIT and colonoscopy for those tested positive was used. The NCSP central unit sent 536,709 invitations to Slovenian residents age 50 to 69 years old between 2009 and 2011. The adherence rate was 56.9% (303,343 participants). FIT was positive in 6.2% (15,310) of the participants (men, 7.8%; women, 5.0%; P<0.01). A total of 13,919 unsedated colonoscopies were performed with the cecal intubation rate of 97.8%. RESULTS: The overall adenoma detection rate was 51.3% [95% confidence interval (CI), 50.5%-52.1%] of which 61.0% (95% CI, 59.9%-62.1%) was in men, and 39.1% (95% CI, 37.8%-40.3%) in women (P<0.01). The mean number of adenoma per positive colonoscopy was 1.94 (95% CI, 1.90-1.97). Adenoma, advanced adenoma, or cancer were found in 7732 (55.5%) colonoscopies. A total of 862 (6.2%) CRC cases were found. Only 161 (18.7%) carcinomas were situated in the right colon. A total of 597 (70.2%) patients with cancer were in the early clinical stages (N, negative; 194 22.8%) of all cancers were cured with only endoscopic resection. CONCLUSIONS: In the NCSP, CRC was found in 6.2% of those participants attending colonoscopy, with 81.3% of carcinomas found in the left colon. A localized clinical stage was found in 70.2% participants. In 22.8% of CRC patients, cancer was cured with endoscopic resection only.

Preeclampsia with and without intrauterine growth restriction-Two pathogenetically different entities?

OBJECTIVE: The objective of this study is to determine the differences in histopathological features of basal decidua and placenta in cases of preeclampsia with or without fetal intrauterine growth restriction (IUGR). METHODS: A prospective case-control study included a study group consisting of 30 pregnant women with preeclampsia completed by cesarean section (CS), in 19 of whom preeclampsia was associated with IUGR, and in 11 it was not. The control group consisted of 20 healthy pregnant women delivered by elective CS. Placentas and samples of placental bed obtained during CS were histopathologically (HP) analyzed after hematoxylin-eosin staining and immunohistochemical labeling of Cytokeratin 7 (CK7) trophoblastic cells in decidua. RESULTS: Regarding the HP changes in the spiral arteries in preeclampsia, the most frequent features were inadequate transformation of spiral arteries with poor trophoblastic invasion (70.0%) and fibrinoid necrosis of the media (66.7%), and rarely acute atherosis (33.3%) and thrombosis (30.0%). Villous hypermaturity was more frequently found in placentas of patients with preeclampsia with IUGR (p < 0.05), while there were no differences between subgroups of preeclampsia with and without IUGR regarding some of HP alterations of placental bed. CONCLUSION: Alterations of the placental bed in terms of decidual vasculopathy are more the characteristics of the preeclampsia itself than IUGR, while changes in placental villi primarily follow the presence of IUGR, which could indicate that preeclampsia with and without IUGR are two pathogenetically different entities.