Aleksandar Stefanovic

The utility of human epididymal protein 4, cancer antigen 125, and risk for malignancy algorithm in ovarian cancer and endometriosis.

Background In women with pelvic mass, cancer antigen 125 (CA125) had not achieved satisfactory sensitivity and specificity in the detection of ovarian cancer, particularly in patients with underlying endometriosis. The aim of this study was to determine the diagnostic potential of human epididymal protein 4 (HE4), the combination of HE4+CA125, and the Risk of Ovarian Malignancy Algorithm (ROMA) for patients with pelvic mass, particularly in differentiating endometriosis from carcinoma. Methods A prospective cross-sectional study was conducted at the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia. Serum samples were obtained preoperatively from 108 women undergoing surgery for pelvic mass; 29 of them had ovarian carcinoma, and 79 had a nonmalignant ovarian disease (39 with benign tumor, 20 with endometriosis, 20 healthy controls). Sera were analyzed for the levels of HE4 and CA125 and were then compared with the final pathologic results. The diagnostic performance of HE4 and CA125 was estimated using receiver operating characteristic curve and area under the receiver operating characteristic curve. Results The level of HE4 and CA125 was significantly higher among the patients with malignant tumors, compared with patients with nonmalignant disease. At the predefined specificity of 95%, HE4 and CA125 showed sensitivity of 65.5% and 58.6%, respectively, whereas the combination of HE4+CA125 reached 68.9% at the same specificity. Importantly, the level of HE4 did not differ significantly between the patients with endometriosis and with other nonmalignant diseases (which was not the case with CA125). Risk of Ovarian Malignancy Algorithm classified 96% of benign premenopausal cases as at low risk for ovarian cancer. Conclusions HE4 showed satisfactory capability of distinguishing endometriosis from ovarian cancer, which CA125 lacked. The Risk of Ovarian Malignancy Algorithm score proved to be useful in excluding malignant diagnosis in premenopausal women.

Analysis of urologic complications after radical hysterectomy

OBJECTIVE Injuries of the ureter or bladder or development of vesicovaginal and ureterovaginal fistulas are the most serious complications in gynecological surgery. STUDY DESIGN This study included 536 women who underwent radical hysterectomy because of invasive cancer of the cervix uteri. RESULTS During the surgery the ureter was injured in 1.32% of cases, whereas the percentage of bladder injuries was 1.49. In the early postoperative period vesicovaginal or ureterovaginal fistulas appeared in 2.61% and 2.43% of cases, respectively. CONCLUSION The stage of the disease, obesity, diabetes, and postoperative surgical infection acted as predisposing factors of the urinary tract complications.

Neonatal outcome in pregnant patients with antiphospholipid syndrome

Abstract Aims: The study aim was to evaluate pregnancy outcomes in patients with antiphospholipid syndrome (APS) and to determine which clinical parameters present risk factors for adverse pregnancy outcomes in these patients. Methods: The study included 55 patients with APS treated at the Clinic for Ob/Gyn, Clinical Center of Serbia, from 2006 to 2012. The control group consisted of 55 healthy pregnant women. Data regarding previous pregnancies and conception method were registered. Immunological and laboratory tests were performed. Pregnancy outcomes, including miscarriage, intrauterine fetal death, hypertensive disorders, diabetes mellitus, phlebothrombosis, fetal growth restriction, premature delivery, delivery method, perinatal asphyxia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis were followed. Results: The premature delivery rate in APS patients was 31.8%, and pregnancy loss was 18.2%. Significantly more patients with APS had thrombocytopenia, pregnancy losses, intrauterine growth restriction, and perinatal asphyxia compared with the control group. More miscarriages, preterm delivery, lower birth weight, preeclampsia, and IgM anticardiolipin antibody levels significantly correlated with adverse pregnancy outcomes. Although rare, respiratory distress syndrome can also worsen neonatal health status. According to ROC analysis, previous miscarriages correctly explained 66.3% of adverse pregnancy outcome cases. We generated four equations of adverse pregnancy outcome risk factors. Conclusions: The most important prognostic factor for pregnancy outcome in APS patients is the number of previous miscarriages. Using appropriate current therapeutic protocol can enable live birth of a healthy newborn in most cases.

Cesarean myomectomy in modern obstetrics: More light and fewer shadows

The study aim was to evaluate management of myomas during cesarean section, the pro and cons and the outcomes of cesarean myomectomy. Moreover, we tried to investigate the long‐term outcomes of cesarean myomectomy. The authors conducted a literature review using scientific databases, focusing on the benefits and outcomes of cesarean myomectomy and the recent trends regarding this topic, and identified relevant articles, related references and other papers citing them. Despite the demonstrated advantages of cesarean myomectomy, postponed myomectomy after cesarean section was recommended in some instances. Apart from recent reports on the safety and feasibility of cesarean myomectomy, the current literature also describes serious complications of cesarean myomectomy, including even maternal death. This poses a question about the reported rate of complications: whether it is underestimated in common practice. Although some studies strongly suggest the safety of cesarean myomectomy, data on the long‐term outcomes of cesarean myomectomy in women are lacking. The risk–benefit ratio of cesarean myomectomy should be re‐evaluated in the new century, given the increasing patient age, incidence of myoma in pregnancy, and the wide use of assisted reproductive techniques.

Fertility sparing therapy for metastatic gestational trophoblastic disease in young patients.

[1] Lemos NA, Arbo E, Scalco R, Weiler E, Rosa V, Cunha-Filho JS. Decreased antiMüllerian hormone and altered ovarian follicular cohort in infertile patients with mild/minimal endometriosis. Fertil Steril 2008;89(5):1064–8. [2] Corson SL, Gutmann J, Batzer FR, Wallace H, Klein N, Soules MR. Inhibin B as a test of ovarian reserve for infertile women. Hum Reprod 1999;14(11):2818–21. [3] Coric M, Barisic D, Pavicic D, Karadza M, Banovic M. Electrocoagulation versus suture after laparoscopic stripping of ovarian endometriomas assessed by antral follicle count: preliminary results of randomized clinical trial. Arch Gynecol Obstet 2011;283(2):373–8. [4] Hansen KR, Hodnett GM, Knowlton N, Craig LB. Correlation of ovarian reserve tests with histologically determined primordial follicle number. Fertil Steril 2011;95(1): 170–5.

Safety of cesarean myomectomy in women with single anterior wall and lower uterine segment myomas

Abstract Objective: Cesarean myomectomy (CM) is a safe procedure in selected cases. Nevertheless, literature lacks clear guidelines on patient selection. We aimed to evaluate CM safety in patients with single anterior wall and lower uterine segment (LUS) myomas. Methods: The authors selected pregnants at term, scheduled for CSs, with single anterior wall or LUS myomas. All their clinical, demographic, obstetric, and surgical parameters were recorded. Results: Thirty-six women had a CM (study group), and 17 had a CS without myoma removal (control group). No significant differences were detected in the socio-demographic and clinical findings between the groups. The average size of myomas in the study and control group (p = .873), was 55.44 mm and 47.25 mm, respectively. The average surgery duration was 62.5 min in the study and 53.82 in the control group (p = .058). Intraoperative hemorrhage was more frequent in the study group (p = .045). Nevertheless, neither the number nor the volume of intraoperative transfusions was significantly different. None of the major CM complications were recorded, and the duration of hospitalization was similar in both groups. Conclusions: CM in patients with single anterior wall and LUS myomas does not cause increased perioperative morbidity, and, therefore, can be considered safe in such cases.

Pathogenesis, Classification, Histopathology, and Symptomatology of Fibroids

Uterine fibroids (leiomyomas or benign tumors of the smooth muscle) represent the most common form of benign mesenchymal disease of the female genital tract. Clinical studies report an incidence of 25–30% of the female population of childbearing age, with higher prevalence after 40 years and in black women [1].

Physiology and Importance of the Myoma’s Pseudocapsule

Many researches addressed the role of uterine myomas in physiology and their negative impact on the women well-being. In the new century, there have been many discoveries in genetics, molecular biology, and pharmacology as part of the understanding of the biological behavior and treatment of myomas. Nevertheless, it is still not entirely clear on the impact of uterine myoma uterus physiology and reproduction. It is not clear, for example, why some myomas grow so fast, why others remain unchanged in size for years, because some negative impacts in women’s health and other patients rather not complain symptoms, even with myomas in the uterus. In the anatomical evaluation of the myoma, there is a structure that is occasionally mentioned in the macro- and microscopic description. In fact, during its growth, myoma induces the progressive formation of a sort of pseudocapsule, due to compression on the surrounding structures and which separates myomas from the healthy uterine tissue. The pseudocapsule cells have the features of smooth muscle cells similar to the myometrium, indicating that the pseudocapsules are part of the myometrium compressed by the myoma. Pseudocapsule is rich of collagen fibers, neurofibers, and blood vessels, as a sort of neurovascular bundle, with a proper angiogenic profile. Pseudocapsule sparing during myomectomy preserves myometrium integrity peripheral to myoma site, enhancing myometrial healing after myomectomy, with a positive impact on successive uterine anatomy restoring patient’s fertility. In this chapter, we discuss the latest scientific evidence relating to the myoma pseudocapsule, demonstrating its importance in the uterine physiology and in surgical technique applied during the myoma enucleating.

Cancer during pregnancy – clinical characteristics, treatment outcomes and prognosis for mothers and infants

Abstract Objective: To assess which obstetrical characteristics and treatment improved outcomes and prognosis of pregnant women with malignancy. Methods: A prospective study, undertaken between 2005 and 2014, involving 35 pregnant women who were diagnosed with malignant tumors during pregnancy. Patients were followed-up for 1 year after delivery. The pregnancy course and outcome and parameters that could influence the condition of mother and fetus were evaluated. Results: Most malignancies were hematological, diagnosed in the second trimester and treated with combined therapy (surgery/adjuvant) after pregnancy. Most fetuses were in good state throughout pregnancy, but were delivered by caesarean section (CS) before term. Adjuvant therapy during pregnancy mostly caused transitory deterioration of fetal conditions. The majority of both mothers and infants were in a good state 12 months postpartum, although numerous mothers were still ill and on therapy. Surviving pregnancy and preventing tumors progression during pregnancy were the best predictors of mothers’ future condition (P=0.022). High birthweight and term delivery were the most important factors for good outcome of the infants (P=0.001). Conclusions: If the tumor is not progressing, pregnancy should be continued as long as possible to obtain adequate birthweight of the infant. Second trimester surgery is safe, while other therapies should preferably be applied after delivery.

A Prospective, Single-Blind, Randomized, Phase III Study to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Soft Tissue Open Surgery

Abstract Background/Purpose: Rapid hemostasis, an essential prerequisite of good surgical practice during surgical bleeding, including soft tissue open surgery, often requires adjunctive treatment. We evaluated the safety and hemostatic effectiveness of a human plasma-derived fibrin sealant (FS Grifols) in soft tissue open surgery. Methods: Patients with moderate soft tissue bleeding during open, urologic, gynecologic or general surgery were studied. The trial consisted of a preliminary phase (to familiarize investigators with the technique for FS Grifols application and the intraoperative procedures required by the clinical protocol) and a primary phase: in both phases, patients were randomized 1:1 to FS Grifols or Surgicel®. The primary efficacy endpoint, based on analysis of subjects in the primary phase of the study, was to evaluate whether FS Grifols was non-inferior to Surgicel® in achieving hemostasis, based on the proportion of subjects in both treatment groups who achieved hemostasis at the target bleeding site (TBS) by 4 min (T4) following the start of treatment application. Safety assessments included adverse events (AEs), vital signs, physical assessments, common clinical laboratory tests, viral markers, and immunogenicity. Results: A total of 224 subjects were randomized (primary phase): FS Grifols (N = 116), Surgicel® (N = 108). The 95% CI at T4 for the ratio of the proportion of patients achieving hemostasis in the two treatment groups was 1.064 (0.934, 1.213), indicating non-inferiority for FS Grifols vs. Surgicel®. The rate of hemostasis at the TBS by T4 in both phases of the study was higher in the FS Grifols treatment group (preliminary phase: 90.2%; primary phase: 82.8%) than in the Surgicel® treatment group (preliminary phase: 78.8%; primary phase: 77.8%). Overall, reported AEs were as expected in surgical patients and were similar between the two treatment groups. Conclusions: This study shows the non-inferiority in time to hemostasis of FS Grifols vs. Surgicel as an adjunct to hemostasis in patients undergoing soft tissue open surgery, and a similar rate of AEs.