Evrim Erdemoglu

Significance of detecting insulin‐like growth factor binding protein‐1 in cervicovaginal secretions: comparison with nitrazine test and amniotic fluid volume assessment

Objectives.  The diagnosis of premature rupture of membranes (PROM) is sometimes challenging, and common diagnostic tests are of limited value in the diagnosis. We aimed to study the accuracy of detecting insulin‐like growth factor binding protein‐1 (IGFBP‐1) in vaginal fluid by a rapid dipstick method in comparison with the nitrazine test and amniotic fluid index (AFI) and we studied the predictivity of these methods on the latency of pregnancy in patients with suspected PROM.

Clinical recommendation radical trachelectomy for fertility preservation in patients with early-stage cervical cancer.

Abstract Radical trachelectomy (RT) is a fertility-sparing procedure with the aim to provide adequate oncological safety to patients with cervical cancer while preserving their fertility. In the current review, indications, development of the procedure, technical aspects, preoperative and postoperative management, and oncological, fertility, and obstetric outcomes are discussed and studied with respect to whether the procedure is performed abdominally or vaginally. Complications of RT, staging, and more conservative alternatives to RT are discussed as well. A systematic MEDLINE search was performed, which yielded 218 articles, of which 75 were selected for further analysis based on the number of patients and the quality of the study. Strict morphologic criteria should be applied to the candidates to maintain oncological safety. When limited to a tumor less than 2 cm in diameter, the overall recurrence rate after vaginal RT is 3% to 6% and the death rate is 2% to 5%. Data on fertility and obstetric outcome are mostly based on the results of patients who underwent vaginal RT. More data are needed to be able to draw the same conclusions for abdominal RT. Fertility seems not to be decreased, but the risk for premature delivery is 2 to 3 times higher compared to women with an intact cervix. In locally advanced cervical tumors with a diameter larger than 2 cm, neoadjuvant chemotherapy followed by RT may be offered after explaining the experimental nature to the patient. In conclusion, RT is an oncologically safe technique in women with early invasive cancer. The rate of term pregnancies still needs improvement. Fertility-preserving treatment of women with tumors larger than 2 cm in diameter can be done by combining neoadjuvant chemotherapy and trachelectomy; however, experience is still limited.

Effects of metformin on mammalian target of rapamycin in a mouse model of endometrial hyperplasia.

OBJECTIVE The effects of metformin on S6K1, which is a crucial effector of mTOR signaling, and on endometrium were studied in a mouse model of endometrial hyperplasia induced by unopposed estradiol or tamoxifen. STUDY DESIGN Forty-eight oophorectomized Balb/c mice were randomly assigned to receive saline, tamoxifen citrate (4 mg/kg), 17-beta estradiol hemihydrate (4 mg/kg), metformin (50 mg/kg), tamoxifen citrate (4 mg/kg) with metformin (50 mg/kg), or estradiol (4 mg/kg) with metformin (50 mg/kg) for 3 days. Histological markers of uterotrophy, including luminal epithelial cell height and density of endometrial glands were quantified for each slide. Immunohistochemical expression of PCNA and S6K1 was evaluated. H-score was used for S6K1 expression. Statistical analysis was performed using Students t-test for comparison of two continous variables and one-way ANOVA for comparison of multiple variables. RESULTS Mice treated either with tamoxifen or estradiol had significantly increased density of endometrial glands and epithelial heights compared to vehicle-only or metformin-only group (p<0.001). Addition of metformin to tamoxifen or estradiol treated mice significantly decreased the density of endometrial glands and epithelial cell heights (p<0.05). Addition of metformin to tamoxifen significantly decreased the H-score of S6K1 (p<0.05) and the immunohistochemical expression of PCNA (p<0.05) in uterine lining epithelium, glandular and stromal cells. Addition of metformin to estradiol significantly decreased the H-score of S6K1 (p<0.05) and the immunohistochemical expression of PCNA (p<0.05) in uterine lining epithelium, glandular and stromal cells. CONCLUSION Metformin seems to have possible antiproliferative effects on the endometrium of estradiol or tamoxifen treated mice via inhibiting the mTOR mediated S6K1 activation.

Current developments for pelvic exenteration in gynecologic oncology.

Purpose of review The present review aims to update new techniques of pelvic exenteration including minimal invasive surgery, and discuss other aspects of this radical surgery, including worldwide differences. Recent findings Major advances are made since the first description of pelvic exenteration and the operation is still under evolution. Explorative laparoscopy prior to exenteration is a valuable alternative to laparotomy to elect candidates for pelvic exenteration. There are considerable differences with respect to indications, contraindications, preoperative staging and adjuvant therapy after exenteration in different countries. Advances in laparoscopic instruments also led to the laparoscopic exenteration. The main limiting step of the operation is urinary diversion. New techniques of laparoscopic-assisted and robotic-assisted techniques of urinary diversion have been reported that decrease the operation time. Vascularized muscle flaps are preferred by many surgeons to fill the empty pelvis and provide an acceptable vaginal reconstruction. J-pouch seems to be a safer technique than end-to-end coloanal anastomosis for bowel reconstruction. Developments in the bioengineering tissue for pelvic reconstruction are required. Summary Laparoscopy has the advantages of decreased blood loss, improved convalescence, lower incidence of wound infection and incisional hernia, short recovery periods, rapid return of bowel function, better pain control and improved cosmetics compared with laparotomy for pelvic exenteration. Magnification and improved visualization permits en-bloc dissection of tumor and good anastomosis technique. New techniques of urinary diversion, orthotopic neobladder and coloanal are promising.

Expression of cyclooxygenase-2, matrix metalloproteinase-2 and matrix metalloproteinase-9 in premenopausal and postmenopausal endometrial polyps.

OBJECTIVES Cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) are influenced by relative levels of estrogen and are involved in promoting cell proliferation and angiogenesis. The present study investigated expression of COX-2, MMP-2 and MMP-9 in endometrial polyps from premenopausal and postmenopausal women. METHODS Premenopausal (n=18) and postmenopausal (n=22) endometrial polyps were included in the study. None of the women were using non-steroid anti-inflammatory drugs, hormone replacement therapy or any other estrogen containing pills. Immunohistochemical analysis for MMP-2, MMP-9 and COX-2 were performed on formalin fixed, paraffin-embedded tissue using the streptavidin-biotin-peroxidase technique. The cut-off value for positiviy was set to 10% and staining more than 50% was regarded as intense staining. Staining of 10-25% and 25-50% were recorded as mild and moderate, respectively. RESULTS COX-2, MMP-2 and MMP-9 were stained in epithelial cells and stroma of premenopausal and postmenopausal endometrial polyps. Stromal expression of COX-2, MMP-2 and MMP-9 were found significantly higher in premenopausal polyps compared to postmenopausal polyps (p<0.05). There were no other significant differences in the immunohistochemical expressions in the epithelium of premenopausal and postmenopausal endometrial polyps except MMP-9. CONCLUSION Polyps from both premenopausal and postmenopausal women express epithelial and stromal COX-2, MMP-2 and MMP-9, however immunohistochemical expression of these markers may be different due to menopausal status. This may suggest a shared pathogenesis for pre- and postmenopausal endometrial polyps.

Physical and Mental Workload in Single-Incision Laparoscopic Surgery and Conventional Laparoscopy

Objectives. The aim of the present study is to evaluate mental workload and fatigue in fingers, hand, arm, shoulder in single-incision laparoscopic surgery (SILS) and multiport laparoscopy. Methods. Volunteers performed chosen tasks by standard laparoscopy and SILS. Time to complete tasks and finger and hand strength were evaluated. Lateral, tripod, and pulp pinch strengths were measured. Hand dexterity was determined by pegboard. Electromyography recordings were taken from biceps and deltoid muscles of both extremities. The main outcome measurement was median frequency (MF) slope. NASA-TLX was used for mental workload. Results. Time to complete laparoscopic tasks were longer in the SILS group (P < .05). Decrease of strength in fingers and hand were similar in SILS and standard laparoscopy. Pegboard time was increased in both hands after SILS (P < .05). MF slope of biceps muscle and deltoid muscle in SILS was far away from the reference slope. MF slope of biceps muscle and deltoid muscle in standard laparoscopy was close to reference slope, indicating there was more fatigue in biceps and deltoid muscles of both upper extremities in SILS group. NASA-TLX score was 73 ± 13.3 and 42 ± 19.5 in SILS and multiport laparoscopy, respectively (P < .01). Mental demand, physical demand, temporal demand, performance, effort, and frustration were, respectively, scored 10.7 ± 3.8, 11.7 ± 3.5, 12.2 ± 2.7, 11 ± 3, 13.6 ± 2.7, and 13.5 ± 2.8 in SILS and 6.3 ± 3.1, 6.6 ± 3.3, 7.3 ± 3.3, 7.1 ± 4.1, 7.9 ± 3.9, and 6.6 ± 3.8 in standard laparoscopy (P < .01). Conclusions. SILS is mentally and physically demanding, particularly on arms and shoulders. Fatigue of big muscles, effort, and frustration were major challenges of SILS. Ergonomic intervention of instruments are needed to decrease mental and physical workload.

Evaluation of the VITOM in digital high-definition video exocolposcopy.

Objective: Our aim was to present our initial clinical experience using a novel exoscopically based colposcopy system (VITOM) for the evaluation of cervical, vulvar, and vaginal diseases. Materials and Methods: Women referred to the Charite Cervix Center, Charite University, Berlin, Germany, were included. Patients with abnormal Pap smear results, vulvar lesions, or a biopsy report of neoplasia of the lower genital tract were included into the study. The VITOM was used for colposcopic evaluation and directed biopsies. Colposcopic findings were reported according to the criteria of the Committee on Nomenclature of the International Federation of Cervical Pathology and Colposcopy. Histologic diagnosis was described as normal, low-grade lesion, high-grade lesion (including cervical intraepithelial neoplasia 2,3, vulvar intraepithelial neoplasia 2,3, vaginal intraepithelial neoplasia 2,3), or cancer. Results: We recruited 76 patients (54 with cervical, 4 with vaginal, and 18 with vulvar disease) to the prospective study. Four patients were pregnant. Of patients with cervical disease, 29% had a history of previous conization and 3.7% had a history of trachelectomy. The sensitivity, specificity, negative predictive value, and positive predictive value of the VITOM for cervical intraepithelial neoplasia 2, 3 were 90%, 77%, 90% and 77%, respectively. Concordance of exocolposcopic impressions and histologic results was higher in high-grade lesions (K = 0.68, 95% CI = 0.32-0.87, p < .001) than in low-grade lesions (K = 0.41, 95% CI = 0.1-0.41, p < .05). Conclusions: Exocolposcopy with the VITOM is accurate and shows good correlation to histologic findings in high-grade disease of the lower genital tract. The potential advantages include patient and trainee involvement in examination, decision making, and documentation.

Effect of inter-twin delivery time on Apgar scores of the second twin

Objective: The aim of the present study was to analyse the effect of inter‐twin delivery time on the Apgar scores of the second twin.

Primary retro peritoneal mucinous cystadenoma

Mucinous cystadenomas and cystadenocarcinomas of the ovary are clinically and histopathologically well-established common tumors. The retroperitoneal location of cystic tumors resembling ovarian mucinous cystadenoma and cystadenocarcinoma is rare. We report the clinical and pathological features of a rare retroperitoneal tumor in the presence of normal ovaries, primary retroperitoneal cystadenoma, and discuss the possible origin of retroperitoneal mucinous cystadenomas.

Leukemia inhibitory factor (LIF) is immunohistochemically localized in tubal ectopic pregnancy

Leukemia inhibitory factor (LIF) is essential for implantation of the embryo in the endometrium. It is not clear whether the blastocyst requires expression of LIF for implantation into tissues other than endometrium. Immunohistochemical localization of LIF was performed in the fallopian tube of 20 women with ectopic pregnancies, 7 women with normal pregnancies and 20 healthy non-pregnant women. Fallopian tubes were evaluated from specimens taken during tubal ligation in normal pregnancies and non-pregnant fertile women or at operation for tubal surgery in ectopic pregnancies. Biopsies were assayed by immunohistochemistry. Semi-quantitative immunohistochemical reaction scores (IRS) were used for immunohistochemical analyses. Immunolabeling of LIF was detected in the surface epithelium and stroma of fallopian tubes in all subjects. IRS score in the epithelium and stroma of non-pregnant women and women with intrauterine pregnancy were similar (p>0.05). However, women with ectopic pregnancy had significantly increased labeling of LIF compared to others (p<0.05). Immunohistochemical labeling of LIF in the fallopian tube was found to be increased in ectopic pregnancies compared to non-pregnant and healthy pregnant controls. This may indicate a role of LIF in the ectopic implantation of embryos.