Roland Csorba

Endometrial cancer: molecular and therapeutic aspects

Endometrial cancer (EC) is the most commonly diagnosed gynecologic malignancy. Although early-stage EC is effectively treated surgically, commonly without adjuvant therapy, the treatment of high-risk and advanced disease is more complex. Chemotherapy has evolved into an important modality in high-risk early-stage and advanced-stage disease, and in recurrent EC. Multi-institutional trials are in progress to better define optimal adjuvant treatment for subsets of patients, as well as the role of surgical staging in reducing both overuse and underuse of radiation therapy. Understanding and identifying the molecular biology and genetics of EC are central to the development of novel therapies. A number of molecular and genetic events have been observed in ECs, which have enabled us to have a better understanding of the biology and development of the disease. For example, the PTEN/AKT pathway and its downstream targets and the mTOR pathway have been shown to play an important role in EC pathogenesis. This review summarizes the background of the known molecular alterations, and the management of patients with EC.

The contribution of catumaxomab in the treatment of malignant ascites in patients with ovarian cancer: a review of the literature

The approval of the first specific drug catumaxomab for the treatment of malignant ascites is the subject of this review. This trifunctional antibody is known to kill EpCAM-positive tumor cells and therefore attacks the primary cause of malignant ascites formation in the peritoneal cavity. Until today catumaxomab is the only EpCam-targeted antibody approved by the European Medicines Agency. Ovarian cancer is caused by epithelial tumors cells which overexpress epithelial cell adhesion molecule (EpCAM). The existing literature concerning the use of catumaxomab for the treatment of malignant ascites associated with ovarian cancer until today is reported in this article. It is very encouraging that different prospective studies from diverse scientific teams recently presented positive results concerning the efficacy and the safety of catumaxomab in the treatment of malignant ascites in patients with ovarian cancer. A case of a patient with ovarian cancer FIGO IIIc is also referred in this article. A complete remission and stable disease was found after 4 i.p. infusions of catumaxomab.

Female child sexual abuse within the family in a Hungarian county.

Background: The aim of the study was to analyze the characteristics of intrafamiliar female child sexual abuse and to explore common features that may be utilized as targets for possible methods of prevention. We also described the medical and legal approaches to handling child neglect. Methods: This was a descriptive, cross-sectional study on 52 sexually abused girls under the age of 18 at the Department of Obstetrics and Gynecology, Medical and Health Science Center of Debrecen. We prospectively recorded the data of all cases. Intrafamiliar events were defined if the victim and perpetrator belonged to the same family. Legal outcomes were also recorded. Results: During the 16-year period, 209 cases of sexual abuse were seen in our clinic, 52 of them had been involved in child sexual abuse within the family. This accounts for 25% of adolescent cases. Eighty-six percent of the victims were pupils, 50% of them were between 11 and 14 years of age. The perpetrator was the victim’s father in 44%, and the stepfather in 40%. There was a slight difference between the type of abuse among the pre- and postpubertal group of victims, but statistically it was not significant. The abuse occurred on multiple occasions in 52%. The occurrence rate of assault was the highest in the summer season (58%), mostly in the afternoon (42%) and it took place almost exclusively at home (98%). The mother accompanied the victim in 38% of the cases and the police in 40%. Vaginal penetration was the type of abuse in 75%, and sexual perversion in 25%. Six victims were physically injured, the presence of sperm could be confirmed on vulvovaginal smears in 2 cases. One pregnancy conceived. Nine cases were reported to the police and as a result of legal proceedings, 5 perpetrators have been sentenced. Conclusion: The majority of crimes take place within the family and are disclosed after multiple episodes. The small proportion of reported sexual assaults is the consequence of the lack of harmony between the Hungarian conditions of emergency care and the criminal law. Prevention calls for attention at all levels of child education, observation at off-school times, early involvement of health professionals, applying standardized medical guidelines and the modification of jurisdiction.

Inherited thrombophilia and reproductive disorders

Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia.

Rheological, hemostaseological changes during immunetherapy for prevention of HELLP-syndrome in a patient with elevated phospholipid antibodies

OBJECTIVE Patients with a history of severe obstetric complications in the presence of elevated phospholipid antibodies are at high risk for recurrent obstetric debacle. We report a successful immunologic treatment for prevention of HELLP-Syndrome in subsequent pregnancy in a patient with elevated Phospholipid antibodies, while under rheological and hemostaseological monitoring. METHODS The patient with prior severe HELLP-Syndrome at term in the presence of reconfirmed elevated phospholipid antibodies in her first pregnancy received pooled immunoglobulins (Sandoglobulin 3 g - Novartis) intravenously for immunological treatment every three weeks in addition to low molecular weight heparin (Clexane 40 mg/d s.c.) and Aspirin (100 mg/d from 2nd trimester) during her subsequent pregnancy. Before each of 10 treatment cycles blood rheological parameters (Red Blood cell {RBC} aggregation stasis E0, low shear E1, RBC - deformability low-, moderate-, and high shear force, plasma viscosity {Pv}), as well as thrombelastometry (ROTEM) and in vitro platelet function (PFA-100) for hemostaseological evaluation was performed. At the same times non-invasive, physical thrombosis screening took place using impedance plethysmography (Filtrass) RESULTS During pregnancy a constant increase in PV and E1 (>45 S -1) was accompanied by a delayed but continuous increase in RBC deformability beginning at the end of the 2nd trimester. Thrombelastometry revealed a continuous reduction of clot formation time (CFT; extem: 84 to 38 sec) and an increase in maximal clot firmness (MCF; extem: 64 to 78 sec) after TF-induced coagulation activation while MCF and CFT after contact activation (intem) was barely unchanged. Platelet bleeding-time after EPI/Coll stimulation was temporary prolonged by the onset of Aspirin intake (>300 sec) but normalized soon after 20th gestational week, while ADP/Coll stimulation revealed a trend towards prolonged bleeding times at the same time. There was a strong and statistically significant inverse correlation between E1 and TF induced CFT (r =-0.82; p = 0.002) and a positive correlation between E1 and TF induced MCF (r = 0.89; p <  0.001), while the correlation between E1 and contact activated CFT and MCF was weak or absent, respectively. Until GW 38th routine laboratory- (Platelet-count, Haptoglobin, liver enzymes) and clinical findings remained normal, without evidence of HELLP-Syndrome reoccurrence or development of thrombosis. CONCLUSIONS During immunotherapy in this high risk patient HELLP-Syndrome did not reoccur. The aggregability of RBC was closely related with the formation speed and firmness of clot after TF activated coagulation but not after contact activated coagulation. At the beginning of 3rd trimester RBC aggregation remained dramatically higher as compared to the normal value range of pregnant women found in a large recent trial which may have been an early indicator of imminent HELLP-Syndrome.

Rheological parameters in the umbilical cord blood in moderate and severe forms of preeclampsia

INTRODUCTION Previous studies have dealt with maternal blood rheology in preeclampsia (PE), but only a few focused on the fetal rheological parameters in this maternal state. PE is one of the most common severe complications of pregnancy world-wide associated with high maternal morbidity and mortality and intrauterine fetal growth restriction. Our objective was to explore the rheological parameters in the umbilical cord blood at term in the presence of moderate and severe forms of PE. METHODS A subgroup analysis was performed in a community based retrospective study of 4,951 consecutively recorded singleton pregnant women of whom 423 had PE. In the latter, umbilical cord blood was collected during delivery for testing of hematological and blood rheological parameters of their fetus. Fetal results from uneventful pregnancy were compared with those associated with preeclampsia. Furthermore, results were also evaluated in the presence of moderate and severe forms of PE. Plasma viscosity (pv) was examined using KSPV 1 Fresenius and Red Blood Cell (RBC) aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. RESULTS According to the definition of the German Society of Gynecology and Obstetrics (DGGG) 314 women had moderate (74.2%), while 109 had severe forms of PE due to the presence of a blood pressure > 170/110 mmHg (n = 41; 9.7%), and/or IUGR < 5th percentile (n = 28; 6.6%), and/or HELLP-Syndrome (n = 10; 2.4%), and/or proteinuria ≥ 5 g/24 h (n = 30; 7.1%). When comparing the fetal results from pregnancies with and without preeclampsia mean hemoglobin values (p < 0.001) and hematocrit (p < 0.001) were markedly higher, while plasma viscosity (p = 0.006) and erythrocyte aggreagtion (stase: p = 0.35; low shear: p = 0.08) were lower in association with preeclampsia. Gestational age, fetal birth-weight and umbilical arterial cord blood pH in women with severe PE was statistically significant lower as compared to those with moderate disease (p < 0.001). Mean hemoglobin level and hematocrit were higher in fetus from women with severe compared to moderate PE, while plasma viscosity (1.03 ± 0.07 mPas vs. 1.05 ± 0.07; p = 0.05) and erythrocyte aggregation in stase (2.3 ± 2.47 vs. 2.41 ± 2.46; p = 0.11) as well as under low shear (7.86 ± 4.63 vs. 8.06 ± 4.60; p = 0.15) were lower. HELLP-Syndrome was associated with the lowest plasma viscosity (1.00 ± 0.07 mPas; p = 0.019) and erythrocyte aggregation (low shear: 5.1 ± 5.0; p = 0.04) in fetus. CONCLUSION The results of this study including a notable number of patients with PE and their newborns revealed an in part statistically significant association between variables of blood rheology and the presence, severity and type of preeclampsia with a trend towards hyperviscosity in severe forms of preeclampsia. The behaviour of blood rheological components in the neonate is remarkable since the number of red blood cells is raised while RBC aggregability and plasma viscosity is low.

Thrombelastometric results and platelet function during pregnancy in women receiving low molecular weight heparin with a history of recurrent/late abortion--A retrospective analysis.

In women with a history of recurrent/late abortion and confirmed genetic/acquired thrombophilia, LMWH was given during subsequent pregnancy and serial coagulation testing was performed.In 82 consecutive pregnant women with recurrent (≥2) and/or late abortion (>12 GW) in the presence of single (n = 62; 75.6%) or combined (n = 20; 24.4%) genetic and/or acquired thrombophilia, Thromboelastometry (n = 50; ROTEM, TEM) and closure-time (n = 82; PFA-100; Siemens) underwent serial testing before and during pregnancy while receiving LMWH and puerperal.Throughout pregnancy, clotting-time (CT) after intrinsic and extrinsic induced coagulation activation in Thromboelastometry remained unchanged. TF-induced coagulation activation resulted in statistically significantly decreased mean clot-formation-times (CFT) (Trim I: 108.9 ± 5.2 S to Trim III; 81.7 ± 5.4 S; p = 0.001), whereas after contact activation (Intem-S: Trim I: 70.1 ± 4.0 S to Trim III: 65.4 ± 6.8; n.s.) CFT remained unchanged. Mean maximal-clot-firmness (MCF) continuously increased in the Intem-S and Extem-S during each trimester and decreased until 4th puerperal week (Extem-S: Trim I: 61.9 ± 1.0 S; Trim II: 65.4 ± 0.58 S; Trim III: 68.3 ± 1.1 S; p <  0.001; Intem-S: Trim I: 64.1 ± 0.6 S; Trim II: 66.8 ± 0.5 S; Trim III: 69.5 ± 1.2 S; p <  0.001). Mean Closure-times after Epinephrine/ADP/Collagen stimulation remained unchanged during pregnancy.In women with different thrombophilia receiving LMWH at prophylactic dose a significant increase in MCF was accompanied by barely unchanged CT after intrinsic and extrinsic coagulation activation and platelet mediated closure-times in the course of the pregnancy. Decrease in CFT was only seen after extrinsic coagulation activation, whereas unchanged CFT after intrinsic coagulation activation may be the result of LMWH given at low dose.

Management of post partum haemorrhage

Primary post partum haemorrhage is the most common form of major obstetric haemorrhage. The traditional definition of primary post partum haemorrhage is the loss of 500 ml or more of blood from the genital tract within 24 hours of the birth of a baby. Post partum haemorrhage can be minor (500-1000 ml) or major (more than 1000 ml). Major could be divided to moderate (1000-2000 ml) or severe (more than 2000 ml). The recommendations in this article apply to women experiencing primary post partum haemorrhage of 500 ml or more. Secondary post partum haemorrhage is defined as abnormal or excessive bleeding from the birth canal between 24 hours and 12 weeks postnatally. The main causes of the secondary form are: inflammations (endometritis), placental tissue retention, inadequate involution of the uterus and malignancy. Because of its importance as a leading cause of maternal morbidity and mortality, obstetric haemorrhage must be considered as a priority topic. According to the tragic and dramatic outcomes of this morbidity, and to the fact that most cases of post partum haemorrhage have no identifiable risk factors, the practical obstetricians should be aware of the accurate diagnosis and management of this illness.

Robotic surgery in gynecology

Minimally invasive surgery has revolutionized gynecological interventions over the past 30 years. The introduction of the da Vinci robotic surgery in 2005 has resulted in large changes in surgical management. The robotic platform allows less experienced laparoscopic surgeons to perform more complex procedures. It can be utilized mainly in general gynecology and reproductive gynecology. The robot is being increasingly used for procedures such as hysterectomy, myomectomy, adnexal surgery, and tubal anastomosis. In urogynecology, the robot is being utilized for sacrocolopexy as well. In the field of gynecologic oncology, the robot is being increasingly used for hysterectomy and lymphadenectomy in oncologic diseases. Despite the rapid and widespread adaption of robotic surgery in gynecology, there are no randomized trials comparing its efficacy and safety to other traditional surgical approaches. This article presents the development, technical aspects and indications of robotic surgery in gynecology, based on the previously published reviews. Robotic surgery can be highly advantageous with the right amount of training, along with appropriate patient selection. Patients will have less blood loss, less post-operative pain, faster recovery, and fewer complications compared to open surgery and laparoscopy. However, until larger randomized control trials are completed which report long-term outcomes, robotic surgery cannot be stated to have priority over other surgical methods.

Neonatal blood rheological parameters at delivery in healthy neonates and in those with morbidities.

Rheological blood parameters of neonates are different form those of adults. Many authors have studied changes in blood rheology in neonates in different clinical disorders. To-date, no one set the normal values for blood rheological parameters in healthy neonates. The aim of this study is to set the norm for rheological blood parameters in healthy newborns and to describe the changes in those parameters in common clinical disorders that affect the newborns. We recruited all the neonates born to mothers experiencing un eventful pregnancies, blood was taken from the umbilical cord right after the delivery. In this time period we recruited 4985 neonate. From this huge database we were able to set the standards for blood rheology in neonates, namely plasma viscosity of 1.06±0.072 mPa, erythrocyte aggregation at stasis of 2.41±2.74 s-1 and erythrocyte aggregation under low shear forces of 8.51±6.38 s-1. These values changed significantly in some diseased neonates. This is the largest study investigating normal rheological parameters and deviations from the norm in common clinical disorders occurring in this early stage of life.