Could the Long-Term Oncological Safety of Laparoscopic Surgery in Low-Risk Endometrial Cancer also Be Valid for the High-Intermediate- and High-Risk Patients? A Multi-Center Turkish Gynecologic Oncology Group Study Conducted with 2745 Endometrial Cancer Cases. (TRSGO-End-001).

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high-intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high-intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high-intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high-intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high-intermediate- and high-risk endometrial cancer cases.

Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes.

OBJECTIVE: In this study, we aimed to evaluate the clinicopathological features, obstetric, and oncological outcomes of patients diagnosed with a uterine smooth muscle tumors of uncertain malignant potential (STUMP). METHODS: A dual-institutional, database review was carried out to screen patients with STUMP who were treated with upfront surgery between January 2006 and December 2017. Data including age at the time of diagnosis, recurrence rate, disease-free survival, overall survival, and fertility outcomes were retrospectively analyzed. RESULTS: Fifty-seven patients with STUMPs were included in the study. The median age at the time of diagnosis was 42 (range, 16 to 75) years. The median follow-up was 57 (range, 16 to 125) months. Eight patients (14%) had recurrence during follow-up. Recurrent STUMPs were seen in seven patients and leiomyosarcoma after 14 months in one patient. Seven patients with a recurrent STUMP survived, while the remaining patient died. Recurrence rates were similar for women who underwent myomectomy and those who underwent hysterectomy. The presence of uterine localization of tumor (subserosal vs intramural-submucosal) statistically significantly affected recurrence rates (odds ratio=5.72; 95% confidence interval=1.349-24.290; p=0.018). Ten of 27 patients who underwent myomectomy for uterine myoma had fertility desire. Seven pregnancies were recorded. CONCLUSIONS: Our study results suggest that fertility-sparing approaches are feasible in patients with STUMP, although recurrence may be seen.

Recurrence patterns and prognostic factors in lymphovascular space invasion-positive endometrioid endometrial cancer surgically confined to the uterus.

OBJECTIVE: The purpose of this study was to determine the patterns of failure and prognostic factors for lymphovascular space invasion (LVSI)-positive endometrioid endometrial cancer (EC) patients in the setting of negative lymph nodes (LNs). MATERIALS AND METHODS: A multicenter, retrospective department database review was performed to identify LVSI-positive patients with disease surgically confined to the uterus at two gynecologic oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. RESULTS: We identified 185 LVSI-positivewomen with negative LNs during the study period. Fifty-five (29.7%) were classified as Stage IA, 94 (50.8%) as Stage IB, and 36 (19.5%) as Stage II. The median age at diagnosis was 59 years and the median duration of follow-up was 44 months. The total number of the recurrences was 12 (6.5%). We observed 5 (2.9%) loco-regional recurrences, 3 (1.5%) retroperitoneal failures, and 4 (2.0%) distant relapses. The 5-year progression-free survival (PFS) was 86.1% while the 5-year overall survival (OS) rate was 87.7%. Grade 3 histology (Hazard Ratio [HR] 2.9, 95% Confidence Interval [CI] 1.02-8.50; p = 0.04), cervical stromal invasion (HR 4.5, 95% CI 1.61-12.79; p = 0.004) and age ≥ 60 years (HR 5.8, 95% CI 1.62-21.32; p = 0.007) were found to be independent prognostic factors for decreased OS. Adjuvant treatment did not appear as a prognostic factor for OS even in univariate analysis. CONCLUSION: The recurrence rate among LVSI-positive endometrioid EC patients is low in the setting of negative LNs. However, one out of three patients with a recurrence experiences distant relapses which usually portend worse outcomes.

Risk Factors for Lymph Node Metastasis among Lymphovascular Space Invasion-Positive Women with Endometrioid Endometrial Cancer Clinically Confined to the Uterus.

INTRODUCTION: We aimed to assess risk factors for lymph node (LN) metastasis among lymphovascular space invasion(LVSI)-positive women with pure endometrioid endometrial cancer (EC) clinically confined to the uterus. METHODS: Medical records of women who underwent primary surgery for EC between 2007 and 2016 at either of 2 gynecological oncology centers were retrospectively reviewed. Patient data were analyzed with respect to LN involvement, and predictive factors for LN metastasis were investigated. RESULTS: 280 patients with surgically staged endometrioid-type EC with LVSI were identified. LN involvement was detected in 88 patients (31.4%) with a systematic LN dissection. In multivariate analysis, elevated baseline serum CA 125 levels, deep myometrial invasion (MMI), adnexal involvement and positive peritoneal cytology were found to be independent risk factors for LN metastasis. In women without deep MMI and elevated baseline serum CA 125 levels, the rate of LN metastasis was 19%. The presence of solely deep MMI increased this probability up to 29.1%. The rate of LN metastasis was found to be 46.8% for women with both deep MMI and elevated baseline serum CA 125 levels. CONCLUSION: These findings may be useful in the decision-making process for LVSI-positive women who are unstaged.

Impact of lymph node ratio on survival in stage IIIC endometrioid endometrial cancer: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in women with stage IIIC endometrioid endometrial cancer (EC). METHODS: A multicenter, retrospective department database review was performed to identify patients with stage IIIC pure endometrioid EC at 6 gynecologic oncology centers in Turkey. A total of 207 women were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 2 groups: LNR1 (≤0.15), and LNR2 (>0.15). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: One hundred and one (48.8%) were classified as stage IIIC1 and 106 (51.2%) as stage IIIC2. The median age at diagnosis was 58 (range, 30-82) and the median duration of follow-up was 40 months (range, 1-228 months). There were 167 (80.7%) women with LNR ≤0.15, and 40 (19.3%) women with LNR >0.15. The 5-year progression-free survival (PFS) rates for LNR ≤0.15 and LNR >0.15 were 76.1%, and 58.5%, respectively (p=0.045). An increased LNR was associated with a decrease in 5-year overall survival (OS) from 87.0% for LNR ≤0.15 to 62.3% for LNR >0.15 (p=0.005). LNR >0.15 was found to be an independent prognostic factor for both PFS (hazard ratio [HR]=2.05; 95% confidence interval [CI]=1.07-3.93; p=0.03) and OS (HR=3.35; 95% CI=1.57-7.19; p=0.002). CONCLUSION: LNR seems to be an independent prognostic factor for decreased PFS and OS in stage IIIC pure endometrioid EC.

Does the primary route of spread have a prognostic significance in stage III non-serous epithelial ovarian cancer?

BACKGROUND: The purpose of this retrospective study was to determine the prognosis of non-serous epithelial ovarian cancer (EOC) patients with exclusively retroperitoneal lymph node (LN) metastases, and to compare the prognosis of these women to that of patients who had abdominal peritoneal involvement. METHODS: A multicenter, retrospective department database review was performed to identify patients with stage III non-serous EOC at 7 gynecologic oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. The patients were divided into three groups based on the initial sites of disease: 1) the retroperitoneal (RP) group included patients who had positive pelvic and /or para-aortic LNs only. 2) The intraperitoneal (IP) group included patients with > 2 cm IP dissemination outside of the pelvis. These patients all had a negative LN status, 3) The IP / RP group included patients with > 2 cm IP dissemination outside of the pelvis as well as positive LN status. Survival data were compared with regard to the groups. RESULTS: We identified 179 women with stage III non-serous EOC who were treated at 7 participating centers during the study period. The median age of the patients was 53 years, and the median duration of follow-up was 39 months. There were 35 (19.6%) patients in the RP group, 72 (40.2%) in the IP group and 72 (40.2%) in the IP/RP group. The 5-year disease-free survival (DFS) rates for the RP, the IP, and IP/RP groups were 66.4%, 37.6%, and 25.5%, respectively (p = 0.002). The 5-year overall survival (OS) rate for the RP group was significantly longer when compared to those of the IP, and the IP/RP groups (74.4% vs. 54%, and 36%, respectively; p = 0.011). However, we were not able to define "RP only disease" as an independent prognostic factor for increased DFS or OS. CONCLUSIONS: Primary non-serous EOC patients with node-positive-only disease seem to have better survival when compared to those with extra-pelvic peritoneal involvement.

The nomogram of prenasal thickness and nasal bone ratio and its relationship with nuchal fold in second-trimester fetal ultrasound.

AIM: We aimed to define the normal values of second-trimester fetal prenasal thickness and nasal bone length ratio (PNT/NBL) in a low-risk Turkish population and investigate the relationship between the increased PNT and nuchal fold (NF). METHOD: We retrospectively reviewed the data of 650 cases considered to be euploid fetuses who presented to our clinic between December 2013 and September 2014 for a second-line ultrasound between 17 and 24 weeks. Their PNT, NBL, NF and biometric (BPD, HC, AC, FL and HL) measurements were recorded. RESULTS: A total of 650 cases considered to be euploid fetuses were included in this study. There was a linear increase in PNT with the gestational weeks (mean value 3.01 at weeks 17-18 and 3.76 at weeks 23-24). The PNT/NB ratio showed a slight decrease in advancing gestational weeks (mean value 0.57 at weeks 17-18 and 0.50 at weeks 23-24). The 95th percentile value of the PNT/NB ratio, independent of the gestational week, was 0.76. The values of both PNT and NF increased with advancing gestational weeks, but there was no statistically linear increase between PNT and NF (R2 : 0.115). CONCLUSION: In this study, we provided a nomogram of the PNT/NB ratio. Both NF thickness and PNT should be dealt with as two separate markers. Although the formation mechanisms are thought to be the same in both of them, a strong linear relationship does not exist between them.

Is the presence of endometriosis associated with a survival benefit in pure ovarian clear cell carcinoma?

BACKGROUND: The purpose of this study was to compare the prognoses of women with pure ovarian clear cell carcinoma (OCCC) arising from endometriosis to those of women with pure OCCC not arising from endometriosis treated in the same manner. METHODS: A dual-institutional, retrospective database review was performed to identify patients with pure OCCC who were treated with maximal or optimal cytoreductive surgery (CRS) followed by paclitaxel/carboplatin chemotherapy between January 2006 and December 2016. Patients were divided into two groups according to the detection of cancer arising in endometriosis or not, on the basis of pathological findings. Demographic, clinicopathological, and survival data were collected, and prognosis was compared between the two groups. RESULTS: Ninety-three women who met the inclusion criteria were included. Of these patients, 48 (51.6%) were diagnosed with OCCC arising in endometriosis, while 45 (48.4%) had no concomitant endometriosis. OCCC arising in endometriosis was found more frequently in younger women and had a higher incidence of early stage disease when compared to OCCC patients without endometriosis. The 5-year overall survival (OS) rate of the patients with OCCC arising in endometriosis was found to be significantly longer than that of women who had OCCC without endometriosis (74.1 vs. 46.4%; p = 0.003). Although univariate analysis revealed the absence of endometriosis (p = 0.003) as a prognostic factor for decreased OS, the extent of CRS was identified as an independent prognostic factor for both recurrence-free survival (hazard ratio (HR) 8.7, 95% confidence interval (CI) 3.15-24.38; p < 0.001) and OS (HR 11.7, 95% CI 3.68-33.71; p < 0.001) on multivariate analysis. CONCLUSION: Our results suggest that endometriosis per se does not seem to affect the prognosis of pure OCCC.

Factors associated with survival after relapse in patients with low-risk endometrial cancer treated with surgery alone.

OBJECTIVE: To determine factors influencing overall survival following recurrence (OSFR) in women with low-risk endometrial cancer (EC) treated with surgery alone. METHODS: A multicenter, retrospective department database review was performed to identify patients with recurrent "low-risk EC" (patients having less than 50% myometrial invasion [MMI] with grade 1 or 2 endometrioid EC) at 10 gynecologic oncology centers in Turkey. Demographic, clinicopathological, and survival data were collected. RESULTS: We identified 67 patients who developed recurrence of their EC after initially being diagnosed and treated for low-risk EC. For the entire study cohort, the median time to recurrence (TTR) was 23 months (95% confidence interval [CI]=11.5-34.5; standard error [SE]=5.8) and the median OSFR was 59 months (95% CI=12.7-105.2; SE=23.5). We observed 32 (47.8%) isolated vaginal recurrences, 6 (9%) nodal failures, 19 (28.4%) peritoneal failures, and 10 (14.9%) hematogenous disseminations. Overall, 45 relapses (67.2%) were loco-regional whereas 22 (32.8%) were extrapelvic. According to the Gynecologic Oncology Group (GOG) Trial-99, 7 (10.4%) out of 67 women with recurrent low-risk EC were qualified as high-intermediate risk (HIR). The 5-year OSFR rate was significantly higher for patients with TTR ≥36 months compared to those with TTR <36 months (74.3% compared to 33%, p=0.001). On multivariate analysis for OSFR, TTR <36 months (hazard ratio [HR]=8.46; 95% CI=1.65-43.36; p=0.010) and presence of HIR criteria (HR=4.62; 95% CI=1.69-12.58; p=0.003) were significant predictors. CONCLUSION: Low-risk EC patients recurring earlier than 36 months and those carrying HIR criteria seem more likely to succumb to their tumors after recurrence.

Luteal phase support after mild ovulation induction with intrauterine insemination: an on-going debate.

OBJECTIVE: To evaluate the effect of luteal phase support (LPS) using progesterone vaginal gel on pregnancy rate (PR) and live birth rate (LBR) during cycles in which controlled ovarian stimulation (COH) was performed using gonadotropins with intrauterine insemination (IUI) cycles in patients with unexplained infertility and polycystic ovarian syndrome. MATERIALS AND METHODS: From 2010 to 2015, all IUI cycles in which COH was performed using gonadotropins were evaluated retrospectively. LPS was not used until July 2013, after which vaginal progesterone gel was applied in the luteal phase of IUI cycles. Both groups of patients were evaluated in terms of the effect of LPS on PR and LBR. RESULTS: In total, 1578 IUI cycles were evaluated, of which 481 were LPS (+) and 1097 LPS (-). PR and LBR per cycle were 10.6% and 7.4%, respectively, in the LPS (+) group, and 11.6% and 7.7%, respectively, in the LPS (-) group (p = 0.31 and p = 0.25). PR and LBR per patient were 17% and 12%, respectively, in the LPS (+) group, and 17.4% and 12.3%, respectively, in the LPS (-) group (p = 0.48 and p = 0.82). CONCLUSIONS: We found no difference in PR and LBR per cycle and per patient according to the use of LPS in IUI cycles in which COH was performed using gonadotropins. Thus, routine use of LPS in gonadotropin-stimulated cycles requires further research involving larger numbers of patients.

Addition of gonadotropin releasing hormone agonist for luteal phase support in in-vitro fertilization: an analysis of 2739 cycles.

OBJECTIVE: Luteal phase is defective in in vitro fertilization (IVF) cycles, and many regimens were tried for the very best luteal phase support (LPS). Gonadotropin releasing hormone (GnRH) agonist use, which was administered as an adjunct to the luteal phase support in IVF cycles, was suggested to improve pregnancy outcome measures in certain randomized studies. We analyzed the effects of addition of GnRH agonist to standard progesterone luteal support on pregnancy outcome measures, particularly the live birth rates. MATERIAL AND METHODS: This is a retrospective cohort study, including 2739 IVF cycles. Long GnRH agonist and antagonist stimulation IVF cycles with cleavage-stage embryo transfer were included. Cycles were divided into two groups: Group A included cycles with single-dose GnRH agonist plus progesterone LPS and Group B included progesterone only LPS. Live birth rates were the primary outcome measures of the analysis. Miscarriage rates and multiple pregnancy rates were the secondary outcome measures. RESULTS: Live birth rates were not statistically different in GnRH agonist plus progesterone (Group A) and progesterone only (Group B) groups in both the long agonist and antagonist stimulation arms (40.8%/41.2% and 32.8%/34.4%, p<0.05 respectively). Moreover, pregnancy rates, implantation rates, and miscarriage rates were found to be similar between groups. Multiple pregnancy rates in antagonist cycles were significantly higher in Group A than those in Group B (12.0% and 6.9%, respectively). CONCLUSION: A beneficial effect of a single dose of GnRH agonist administration as a luteal phase supporting agent is yet to be determined because of the wide heterogeneity of data present in literature. Well-designed randomized clinical studies are required to clarify any effect of luteal GnRH agonist addition on pregnancy outcome measures with different doses, timing, and administration routes of GnRH agonists.

Cerebellar metastasis in squamous cell vulvar carcinoma.

INTRODUCTION: Brain metastasis is rarely seen in gynecologic cancers. It is more rarely encountered in vulvar carcinoma. CASE HISTORY: A 56-year-old postmenopausal women referred our gynecologic oncology unit for the treatment of locally advanced vulvar carcinoma. Twenty-five days after the operation she developed vertigo and nystagmus. Cranial MRI investigation revealed that she had multiple cerebellar metastasis. CONCLUSION: Brain metastasis might be seen in patient with vulvar carcinoma. To the best of our knowledge, this is the first reported case of vulvar carcinoma which developed cerebellar metastasis.