Lymph node dissection in atypical endometrial hyperplasia.

OBJECTIVE: The rate of concomitant endometrial carcinoma in patients with atypical endometrial hyperplasia is high. We aimed to investigate the role of lymphadenectomy in deciding adjuvant treatment in patients with concomitant atypical endometrial hyperplasia and endometrial carcinoma. MATERIAL AND METHODS: Women with atypical endometrial hyperplasia were enrolled in this retrospective study. Lymph node dissection was performed in only some patients who gave informed consent if their surgeon elected to do so, or if the intraoperative findings necessitated. The final histopathologic evaluations of surgical specimens were compared with endometrial biopsy results. RESULTS: Eighty eligible patients were evaluated. Seventy-two (90%) patients had complex hyperplasia with atypia, and 8 (10%) patients had simple hyperplasia with atypia. Hysterectomy and bilateral salpingo-oophorectomy were performed to all patients; 37 also underwent lymph node dissection. Lymph node dissection was extended to the paraaortic region in 9 of 37 patients. The concomitant endometrial carcinoma rate was 50%. Two patients had lymph node metastasis. Among 40 cases of carcinoma, 17 had deep myometrial invasion and/or cervical or ovarian involvement or grade 2 tumors with superficial myometrial invasion on hysterectomy specimens; 27.5% of all carcinomas were stage Ib or higher. CONCLUSION: The concomitant endometrial carcinoma rate was high in patients with atypical endometrial hyperplasia. Nearly half of these patients had risk factors for extrauterine spread. Lymph node dissection might be helpful to decide adjuvant treatment.

Study of uterine and fetal hemodynamics in response to labor induction with dinoprostone in prolonged pregnancies with normal amniotic fluid and oligohydramnios.

OBJECTIVE: We investigated the effects of labor induction with Dinoprostone on uteroplacental and fetal circulations with Doppler velocimetry in prolonged pregnancies with and without oligohydramnios. METHODS: We performed Doppler evaluations of Uterine A, Umbilical A and Middle Cerebral A. (MCA) in 117 patients (27 associated with oligohydramnios) just before and 6 h after the administration of Dinoprostone. We compared two groups with Mann Whitney U Test and Independent Sample T Test. RESULTS: Uterine Artery Doppler indices of both groups obtained before the medication were compared. All indices were within normal range; however Umbilical A. S/D and PI were higher in oligohydramnios group, approaching statistical significance (p=0.07 for S/D and p=0.03 for PI). All of the Uterine A. Doppler indices significantly increased after the administration of Dinoprostone ovule in normal amniotic fluid index (AFI) group (p=0.00). Doppler indices of the other arteries in this group did not change significantly. Similarly, none of the Doppler indices of all investigated arteries in oligohydramnios group changed significantly. Changes in all measured Doppler indices were minor and similar in both groups. CONCLUSIONS: Labor induction with Dinoprostone in prolonged pregnancies complicated with oligohydramnios is as safe and effective as it is in prolonged pregnancies with normal AFI.

Association of serum estradiol levels on the day of hCG administration with pregnancy rates and embryo scores in fresh ICSI/ET cycles down regulated with either GnRH agonists or GnRH antagonists.

PURPOSE: To investigate the interrelation between serum E2 level on hCG day, score of transferred embryos and pregnancy achievement. METHODS: Records of 350 women aged 18-40 years who underwent ovarian hyperstimulation in fresh cycles down regulated either with GnRH agonist (n = 70) or GnRH antagonist (n = 280) followed by oocyte pick-up, ICSI and embryo transfer are retrospectively analyzed. RESULTS: Median E2 levels on hCG day of cycles ending with and without pregnancy were similar (p = 0.308). ROC curve for AUC of E2 on hCG day with dependent variable pregnancy rate also demonstrated that the E2 level on hCG day cannot be used to predict pregnancy in IVF/ICSI cycles (AUC 0.532, 95 % confidence interval: 0.471-0.593). Grouping cycles according to their E2 levels on hCG day also did not demonstrate any detrimental effect of either low or high E2 levels on hCG day both in agonist and antagonist cycles. Pregnancy rates are strongly correlated with mean and total score of transferred embryos. Interrelation of E2 on hCG day and pregnancy rate is independent from score of transferred embryos. CONCLUSIONS: E2 on hCG day is not correlated with pregnancy rates and cannot be used to predict pregnancy in neither agonist nor antagonist cycles, no matter its level or percentile is used.

Roles of E-cadherin and cyclooxygenase enzymes in predicting different survival patterns of optimally cytoreduced serous ovarian cancer patients.

The relation between cyclooxygenase enzymes and E-cadherin, along with the roles of these markers in the prediction of survival in optimally cytoreduced serous ovarian cancer patients was investigated. Individuals who underwent primary staging surgery and achieved optimal cytoreduction (largest residual tumor volume<1 cm) constituted the study population. Specimens of 32 cases were immunohistochemically examined for cyclooxygenase-1, cyclooxygenase-2, and E-cadherin. Two could not be evaluated for E-cadherin and cyclooxygenase-1. Overall, 14/30, 19/30, and 15/32 cases were positive for E-cadherin, cyclooxygenase-1, and cyclooxygenase-2, respectively. The expressions of E-cadherin and cyclooxygenase-2 were inversely correlated (p:0.02). E-cadherin expression was related with favorable survival (p<0.001). The relation between the expression of cyclooxygenase enzymes and poor survival did not reach statistical significance. On multivariate analysis, E-cadherin appeared as an independent prognostic factor for survival. In conclusion, E-cadherin expression is strongly linked with favorable survival. E-cadherin and cyclooxygenase 2 may interact with each other during the carcinogenesis-invasion process. Further studies clarifying the relation between E-cadherin and cyclooxygenase enzymes may lead to new preventive and therapeutic targets in ovarian cancer.

Detection of IL-1ß in culture media supernatants of pre-implantation human embryos; its relation with embryo grades and development.

In this study, we aimed to determine whether human embryos secrete interleukin-1ß (IL-1ß) into culture media and its correlation with embryo grade and development. Culture media supernatants of 100 embryos obtained from 39 cycles of 38 patients and cultivated individually were collected 2 and 3 days after intracytoplasmic sperm injection (ICSI). IL-1ß concentrations of samples were determined with ELISA and compared with embryo grades and blastomere numbers. Embryo grades and the amount of IL-1ß they secreted were found not to be correlated (p:0.559). Numbers of blastomeres each embryo had at 2nd and 3rd days were found to be correlated with IL-1ß secreted (p:0.00 and p:0.00, respectively). Mean amount of IL-1ß secreted by the embryos from ejaculated sperm cycles were found to be significantly higher than that of embryos from TESE cycles (p:0.016). Patient age and etiology of infertility were not correlated with the amount of IL-1ß secreted and embryo grade. In conclusion, preimplantation human embryos secrete IL-1ß in their media in amounts correlated with their blastomere numbers.

Comparison of hysterosalpingography and hysteroscopy in the evaluation of the uterine cavity in patients undergoing assisted reproductive techniques.

OBJECTIVE: To investigate the diagnostic value of hysterosalpingography (HSG) for intracavitary and structural uterine pathologies in comparison with hysteroscopy (HS) in patients undergoing intracytoplasmic sperm injection-embryo transfer and also to specify the patients who should be subjected to HS in the early stages of an infertility work-up. DESIGN: Retrospective analysis. SETTING: IVF unit of a university hospital. PATIENT(S): Three hundred fifty-nine consecutive women who underwent both HSG and HS for infertility investigation. INTERVENTION(S): HS and HSG. MAIN OUTCOME MEASURE(S): HS findings. RESULT(S): HSG shows a sensitivity of 21.56%, specificity of 83.76%, positive predictive value of 55.26%, and negative predictive value of 70.75%. Its false-negative rate is 78.43%, and its false-positive rate is 16.23%. Overall agreement between the two procedures is 68.9%. The risk of abnormal HS increases with advancing patient age and duration of infertility. Risk increments associated with patient age over 35 years and increasing number of previous assisted reproductive techniques (ART) persist even in the presence of a normal HSG. As expected, we encounter significantly less abnormal HS in the male factor infertility group. CONCLUSION(S): HS should be performed especially in patients older than 35 years of age and/or with a history of two or more previous ART trials even in the presence of a normal HSG. HSG shows unconvincing diagnostic value for intracavitary and structural uterine pathologies in infertility evaluation.

The role of low-molecular-weight heparin in recurrent implantation failure: a prospective, quasi-randomized, controlled study.

Low-molecular-weight heparin did not provide any beneficial effect on pregnancy outcomes in patients with two or more implantation failures. Further trials are needed to confirm a trend in favor of low-molecular-weight heparin in the subgroup with women with three or more implantation failures.

Surgical second-look in epithelial ovarian cancer: high recurrence rate after negative results and lack of survival benefit limits its role in standard management.

OBJECTIVE: To evaluate the role of surgical second look (SSL) in epithelial ovarian cancer. MATERIAL AND METHODS: One hundred and seventy-one patients clinically free of disease were assessed retrospectively. Ninety-eight (57.3%) patients underwent SSL and 73 (42.7%) were observed. Fifty-one (52.0%) of the SSL operations were negative, 31 (31.6%) microscopically positive, and 16 (16.3%) macroscopically positive. Cytoreduction and/or chemotherapy were administered after positive SSL. Negative SSL and observation group patients were observed without treatment until recurrence was detected. Disease free survival (DFS), overall survival (OS) and clinical characteristics of groups were compared. RESULTS: While DFS and OS of negative SSL group were better than the observation, microscopic and macroscopic positive SSL groups (p<.01), no significant difference was found between positive SSL and observation groups (p>.05). However, DFS and OS of the microscopic positive SSL group were significantly longer than the macroscopic positive SSL group (p<.01). Thirty-two patients have had recurrences (62.8%) after negative SSL. Only the use of paclitaxel as first-line chemotherapy was seen to prevent recurrence after negative SSL (p<.05). Recurrence after negative SSL was not affected by stage, grade, age, CA-125 level, ascites volume, histologic type or optimal cytoreduction. CONCLUSION: Rate of recurrence after negative SSL remains high, and secondary efforts following positive SSL could not lead to an obvious survival benefit. Therefore, routine use of SSL seems ineffective and unnecessary.

Pretreatment with octreotide modulates iNOS gene expression, mimics surgical delay, and improves flap survival.

We aimed to evaluate the role of a synthetic somatostatin analogue in delay procedure of experimental skin flaps. Thirty-six rats were randomly divided into 2 groups of 18 each to compare the possible local ischemic effect of octreotide with that of surgical delay in the dorsal random pattern skin flap model. The inducible nitric oxide synthase gene expression was assessed in the flap territory at intervals of immediate, 24 and 48 hours after preconditioning. Histologic analysis was performed in rats at 48th hour and 3 additional rats were used for microangiography. A gradual increase of daily transcript levels was detected in both groups (P < 0.05). The differences of molecular and histologic findings between the groups were not distinctive. Pharmacologically preconditioned rat displayed relevant microvascular features. Forty rats were further grouped randomly into 4 groups of 10 each. In group 1 rats, flaps were raised and reinserted without any prior intervention. Group 2 rats underwent surgical delay procedure, whereas flap territories of the others received either saline solution or octreotide 1 week before the ultimate flap harvest. After another 7-day period, both delay procedures were found effective in improving flap viability (P < 0.01). Ischemia induced by octreotide favored to investigate its utility in delay phenomenon. Although it was not as effective as the surgical delay procedure, it may be a safe pharmacologic alternative to improve the flap survival.

Apoptosis-inducing effects of Morinda citrifolia L. and doxorubicin on the Ehrlich ascites tumor in Balb-c mice.

Morinda citrifolia L. (Noni) is a herbal remedy with promising anti-cancer properties. However, its effects on various cancers are to be investigated to make a firm conclusion before implementing it into the clinical practice. Therefore, we investigated the cytotoxic potential of noni on Ehrlich ascites tumor grown in female Balb-c mice and also combined it with a potent anti-cancer agent, doxorubicin. One group received noni only (n = 8), another one doxorubicin (n = 8), and the other one noni + doxorubicin (n = 8) for 14 days after the inoculation of cells. The control group (n = 7) received 0.9% NaCl only. We found that short and long diameters of the tumor tissues were about 40-50% smaller, compared to those in control group. This anti-growth effect resulted from the induction of apoptosis, which was confirmed by the positive results from the Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) analysis and the active caspase-3 cells in tissues. Apoptosis also confirmed by caspase-cleaved cytokeratin 18 elevation in serum of the treated groups. Further, the proliferation was decreased, which was immunohistochemically shown by the PCNA staining. We conclude that noni may be useful in the treatment of breast cancer either on its own or in combination with doxorubicin. Further studies are warranted to assess the dosage and safety of using noni fruit juice in conjuction with anti-cancer drugs against breast cancer.

Heterotopic cesarean scar pregnancy: how should it be managed?

Heterotopic cesarean scar pregnancy is an extremely rare condition that may cause life-threatening complications. A 24-year-old woman gravida 2, para 1, presented with vaginal bleeding. Vaginal sonography demonstrated 2 gestational sacs containing viable embryos, one located in the uterine fundus and the other in the previous cesarean scar. Fetal reduction of the cesarean scar pregnancy was performed with intracardiac KCl injection and the ongoing intrauterine pregnancy was delivered by cesarean section at 34 week's gestation. To prevent serious complications and preserve intrauterine pregnancy, heterotopic cesarean scar pregnancy must be diagnosed early in gestation. Favorable pregnancy outcome can be achieved with conservative management. However, such management increases the risk of massive bleeding during ongoing pregnancy and cesarean section.

Cervical intramural ectopic pregnancy.

OBJECTIVE: To describe a cervical intramural ectopic pregnancy. DESIGN: Case report. SETTING: Maternity hospital. PATIENT(S): A 28-year-old multiparous woman was seen with vaginal bleeding and a positive urinary pregnancy test after delayed menstruation. Ultrasonography and pelvic examination revealed an empty uterine cavity and a hyperechoic focus within an enlarged cyanotic anterior cervical lip. Vaginal bleeding was controlled with aspiration curettage; however, macroscopic and ultrasonographic views of the cervix remained the same. One week later the anterior cervical lip was found to be ruptured. INTERVENTION(S): Decidual tissue was removed from the ruptured area. MAIN OUTCOME MEASURE(S): Histopathologic confirmation of chorionic villi and presence of a connection between the endocervix and the ruptured area. RESULT(S): No connection was found with the endocervical channel when controlled with a 1-mm Hegar uterine dilator, and histopathologic examination of removed materials revealed chorionic villi. CONCLUSION(S): The cervical intramural ectopic pregnancy is an extraordinary clinical situation and might lead to diagnostic and therapeutic challenges.

Serum levels of adenosine deaminase and pregnancy-related hormones in hyperemesis gravidarum.

OBJECTIVES: We investigated the correlation between pregnancy-related hormones and serum adenosine deaminase (indicator of cellular immunity) level in women with hyperemesis gravidarum. MATERIALS AND METHODS: Twenty patients with hyperemesis gravidarum and 20 normal pregnancies were included in this prospective, case-control study. Serum adenosine deaminase levels, hematological parameters (white blood cells, neutrophil, monocyte and lymphocyte counts) and hormone levels (prolactin, progesterone, thyroid stimulating hormone, human chorionic gonadotropin beta subunit, estradiol (E2)) were measured in all women. Interrelations of blood cell counts and hormone levels with serum adenosine deaminase levels were also investigated. RESULTS: Serum adenosine deaminase, human chorionic gonadotropin beta subunit, thyroid stimulating hormone, E2, progesterone and prolactin levels, and lymphocyte and monocyte counts in women with hyperemesis gravidarum were significantly higher than in controls but white blood cells, neutrophil, T3 and T4 levels were not different. Serum adenosine deaminase level correlated with E2, progesterone, lymphocyte, and monocyte levels for all patients. CONCLUSION: Elevated serum adenosine deaminase in patients with hyperemesis gravidarum may relate to high levels of E2 and progesterone.

Aggressive mixed type endometrial carcinoma in a young woman with rapid progression and fatal outcome.

INTRODUCTION: Endometrial carcinoma in young ages is uncommon and tends to be a well differentiated endometrioid type and has an excellent prognosis. Nevertheless, in this report mixed type endometrial cancer including serous, clear cell and endometrioid components in a young patient with rapid progression and fatal outcome is presented. CASE: A 26-year-old virgin female was admitted with menometrohagia lasting for 9 months, leading to severe anemia. Transabdominal ultrasonography demonstrated 30 x 27 mm intramural mass consistent with leiomyoma in uterine corpus posterior. The patient did not permit any vaginal intervention including endometrial sampling, therefore laparotomy was decided. Mixed type endometrial carcinoma was diagnosed and she was treated with comprehensive surgery plus adjuvant chemotherapy. After 7 months of surgery she deceased. CONCLUSION: We suggest that persistent uterine bleeding associated with severe anemia should be evaluated for malignancy even in young women to avoid delay in diagnosis. Imaging studies especially magnetic resonance imaging may be helpful when endometrial sampling cannot be done.

Absence of endometrium as a cause of primary amenorrhea.

OBJECTIVE: To describe congenital endometrial absence. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 32-year-old woman presented with primary amenorrhea and infertility. Hormone analysis, physical and gynecologic examinations, transvaginal ultrasonography, and karyotype analysis were normal. INTERVENTION(S): Progesterone challenge test, laparoscopy, hysteroscopy were performed, and hysteroscopic biopsies were obtained from the uterine cavity. MAIN OUTCOME MEASURE(S): Presence of endometrium, menstruation. RESULT(S): The progesterone challenge test was negative. Laparoscopy revealed normal pelvic structures. Evaluation of biopsies from uterine cavity revealed absence of endometrium. CONCLUSION(S): Endometrial absence is a differential diagnosis for primary amenorrhea; assessment of the uterine cavity and obtaining biopsy samples may help in diagnosis of suspected cases before they undergo assisted reproduction and can avoid unnecessary treatment.

Primary ovarian leiomyosarcoma: a review of the clinical and immunohistochemical features of the rare tumor.

UNLABELLED: Primary pure ovarian leiomyosarcomas constitute a malignant subgroup of ovarian smooth muscle tumors which comprise only 1% of ovarian tumors. Their origin, etiology, histologic features, clinical behavior, and optimal treatment are still obscure. Malignant behavior is almost always associated with any 2 of coagulative necrosis, cellular atypia, and mitotic index greater than 10. Immunohistochemical and electron microscopic evaluations may improve diagnostic accuracy. Traditionally, International Federation of Gynecology and Obstetrics (FIGO) staging and treatment of ovarian sarcomas have been the same as for epithelial ovarian carcinomas. Although surgery was performed for all cases, the extent of surgery is debatable. Benefit and modality of adjuvant therapy is controversial. The prognosis of primary pure ovarian leiomyosarcomas is extremely poor depending on tumor stage, tumor size, grade, and mitotic index and mostly recurs in abdomen and pelvis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state how rare primary ovarian leiomyosarcoma (POLMS) is, explain that because of its rarity the best diagnostic and treatment modalities are not conclusive, and recall that the authors reviewed the literature to bring the readership current on POLMS.

Effects of orlistat and its relationship with nitric oxide in the small intestinal mucosa.

Nitric oxide (NO) is known to be a messenger molecule that plays an important role in physiological and pathological conditions. It is synthesized by an enzyme called nitric oxide synthase (NOS). Inducible NOS (iNOS), one of the three isomers of NOS, has both protective and toxic properties. In this study, the role of NO has been evaluated by gastrointestinal symptoms induced by orlistat which is used in obesity treatment. Orlistat was given to Wistar rats with and without iNOS inhibition. The effects of orlistat and inhibition of NOS were studied. Glucose, urea, alanine transaminase (ALT), and gamma glutamil transpeptidase (GGT) were descreased after short- and long- term orlistat applications. Dexamethasone increased level of these enzymes. Cholesterol and triglyceride were increased in all experimental groups than the controls. This increment was more severe in animals received orlistat and dexamethasone together. Small intestinal tissue also were researched histologically and NADPH-diaphorase (NADPH-d) histochemistrically. Orlistat caused histological damages in brush border membranes, connective tissues of villi, and lymphocyte migration also increased. Dexamethasone treatment prevented these damages partially while orlistat increased the NOS distribution in the tissue sections. Dexamethasone, which is an iNOS inhibitor, decreased NADPH-d histochemistry. There was a similiar NOS distribution both in the control and orlistat+dexamethasone group. Hence, we concluded that long- term trials with orlistat and similar drugs are needed.