Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006).

INTRODUCTION: This study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. METHODS: Two hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. RESULTS: Surgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. CONCLUSION: SLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care.

Comparison of two intraoperative examination methods for the diagnosis of sentinel lymph node metastasis in clinically early stage endometrial cancer: A Turkish Gynecologic Oncology Group Study (TRSGO-SLN-003).

OBJECTIVE: This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. STUDY DESIGN: Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. RESULTS: Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. CONCLUSION: Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.

Can risk groups accurately predict non-sentinel lymph node metastasis in sentinel lymph node-positive endometrial cancer patients? A Turkish Gynecologic Oncology Group Study (TRSGO-SLN-004).

BACKGROUND AND OBJECTIVES: The purpose of this study was to find out the risk factors associated with non-sentinel lymph node metastasis and determine the incidence of non-sentinel lymph node metastasis according to risk groups in sentinel lymph node (SLN)-positive endometrial cancer patients. METHODS: Patients who underwent at least bilateral pelvic lymphadenectomy after SLN mapping were retrospectively analyzed. Patients were categorized into low, intermediate, high-intermediate, and high-risk groups defined by ESMO-ESGO-ESTRO. RESULTS: Out of 395 eligible patients, 42 patients had SLN metastasis and 16 (38.1%) of them also had non-SLN metastasis. Size of SLN metastasis was the only factor associated with non-SLN metastasis (p = .012) as 13/22 patients with macrometastasis, 2/10 with micrometastasis and 1/10 with isolated tumor cells (ITCs) had non-SLN metastasis. Although all 4 metastases (1.8%) among the low-risk group were limited to SLNs, the non-SLN involvement rate in the high-risk group was 42.9% and all of these were seen in patients with macrometastatic SLNs. CONCLUSIONS: Non-SLN metastasis was more frequent in higher-risk groups and the risk of non-SLN metastasis increased with the size of SLN metastasis. Proceeding to complete lymphadenectomy when SLN is metastatic should further be studied as the effect of leaving metastatic non-SLNs in-situ is not known.

Perioperative Duloxetine for Pain Management After Laparoscopic Hysterectomy: A Randomized Placebo-Controlled Trial.

STUDY OBJECTIVE: To evaluate the effect of perioperative duloxetine on pain management in patients recovering from laparoscopic hysterectomy. DESIGN: A randomized placebo-controlled trial. SETTING: A university hospital. PATIENTS: Of 100 patients enrolled, 80 were randomized 1:1 to receive perioperative duloxetine (n = 40) or placebo (n = 40). INTERVENTIONS: Patients undergoing laparoscopic hysterectomy for benign conditions from November 2017 through March 2018 received 2 doses of 60 mg duloxetine or placebo 2 hours before and 24 hours after surgery. MEASUREMENTS AND MAIN RESULTS: The Quality of Recovery (QoR)-40 questionnaire was completed by participants after discharge. Study and control groups were compared in terms of questionnaire scores, opioid analgesic use, and hospital length of stay. The baseline characteristics of the groups were comparable; median total QoR-40 scores were 111 of 200 and 112 of 200 for duloxetine and the placebo group, respectively; the difference did not reach statistical significance (p = .91). Although the physical independence subcomponent of the recovery questionnaire was improved in favor of duloxetine, none of the subcomponents reached statistical difference between groups. The groups did not differ in terms of postoperative narcotic analgesic use and hospital length of stay (p >.05). CONCLUSION: Perioperative duloxetine did not reduce pain, need for narcotic analgesia, or hospital length of stay following laparoscopic hysterectomy.

Sentinel lymph node biopsy in early stage endometrial cancer: a Turkish gynecologic oncology group study (TRSGO-SLN-001).

OBJECTIVE: The aim of this multicenter study was to evaluate the feasibility of sentinel lymph node (SLN) mapping in clinically uterine confined endometrial cancer. METHODS: Patients who underwent primary surgery for endometrial cancer with an SLN algorithm were reviewed. Indocyanine green or blue dye was used as a tracer. SLNs and/or suspicious lymph nodes were resected. Side specific lymphadenectomy was performed when mapping was unsuccessful. SLNs were ultrastaged on final pathology. RESULTS: 357 eligible patients were analyzed. Median age was 59 years. Median number of resected SLNs was 2 (range 1-12) per patient. Minimal invasive and open surgeries were performed in 264 (73.9%) and 93 (26.1%) patients, respectively. Indocyanine green was used in 231 (64.7%) and blue dye in 126 (35.3%) patients. The dyes were injected into the cervix in 355 (99.4%) patients. The overall and bilateral SLN detection rates were 91.9% and 71.4%, respectively. The mapping rates using indocyanine green or blue dye were comparable (P=0.526). There were 43 (12%) patients with lymphatic metastasis. The SLN algorithm was not able to detect 3 of 43 patients who had isolated paraaortic metastasis. After SLN biopsy, complete pelvic lymphadenectomy was performed in 286 (80.1%) patients. Sensitivity and negative predictive value were both 100% for the detection of pelvic lymph node metastases. In addition, 117 (32.8%) patients underwent completion paraaortic lymphadenectomy after SLN biopsy. In these patients, sensitivity for detecting metastases to pelvic and/or paraaortic lymph nodes was 90.3% with a negative predictive value of 96.6%. The risk of non-SLN involvement in patients with macrometastatic SLNs, micrometastatic SLNs, and isolated tumor cells in SLNs were 61.2%, 14.3% and 0%, respectively. CONCLUSIONS: SLN biopsy had good accuracy in detecting lymphatic metastasis. However, one-third of cases with metastatic SLNs also had non-SLN involvement and this risk increased to two-thirds of cases with macrometastatic SLNs. The effect of leaving these nodes in situ on survival should be evaluated in further studies.

Laparoscopic assisted robotic myomectomy of a huge myoma; Does robotic surgery change the borders in minimally invasive gynecology?

Today, the adoption of minimal invasive gynecologic procedures is expanding their routine use in clinical practice. Until recently, a diameter of 8 cm was the recommended maximal size for laparoscopic removal of fibroids. However, robot-assisted laparoscopy improved the capacity and the feasibility of the many gynecologic procedures. Here, we report a video of robotic myomectomy of a huge myoma.

Microcystic, elongated, and fragmented pattern of invasion in relation to histopathologic and clinical prognostic factors in endometrioid endometrial adenocarcinoma.

OBJECTIVE: To investigate the association of microcystic, elongated, and fragmented (MELF) pattern of invasion with prognostic factors in endometrioid endometrial adenocarcinoma (EEA). MATERIAL AND METHODS: Stained tissue sections from 83 cases of EEA operated by the same gynecologic oncologist were reviewed to identify cases showing MELF-type invasion in this retrospective study. The association of MELF pattern with age, tumor grade, depth of myometrial invasion, and presence of lymphovascular space invasion (LVSI) was analyzed. RESULTS: FIGO grade 2 and grade 1 tumors were evident in 53.0% and 38.6% of patients, respectively. Depth of myometrial invasion was <50% in 72.0% of patients, and LVSI was absent in 77.1%. MELF pattern was confirmed in 35 (42.2%) patients. Presence of MELF pattern was associated with significantly higher mean ± standard deviation age (62.9±6.9) years vs. 58.9±9.1 years, p=0.033), and found to be more likely in patients with high-grade tumor (FIGO grade III; 85.7% vs. 14.3%, p<0.001), deep (≥50%) myometrial invasion (78.3% vs. 21.7%, p<0.001), and presence of LVSI (94.7% vs. 5.3%, p<0.001) as compared with absence of MELF pattern. CONCLUSION: In conclusion, our findings revealed a high rate of MELF pattern among patients with EEA alongside the association of MELF pattern with poor prognostic factors such as high grade tumor, deep myometrial invasion, and LVSI.

Cervical premalignant lesions and their management.

Cervical cancer is the tenth most common cancer in women in developed countries that have national screening programs, while it is in the second line in underdeveloped countries. According to Ministry of Health registry data, cervical cancer is the eighth most common cancer among female cancers in Turkey. Today, the most effective screening for cervical cancer is to obtain smears from the cervix. Therefore, periodic screening programs are of great importance in identifying preinvasive lesions to prevent their progression to invasive cancer. Today, with the use of human papilloma virus (HPV) vaccine, screening programs have brought new insights into the prevention of cervical cancer. Management of preinvasive lesions has to be known by each obstetrics and gynecology specialist. Redundant procedures and treatments can be avoided by directing patients correctly at this step. Cancer phobia should not be created. Ablative or destructive treatments should not be done without histological diagnosis; hysterectomy, which has an equal risk of recurrence, should not be recommended.

Comparison of FIGO 1988 and 2009 staging systems for endometrial carcinoma.

The objective of this study was to compare FIGO 1988 and 2009 endometrial carcinoma staging systems in terms of patient distribution and efficacy in predicting prognosis in patients treated with surgery and adjuvant radiotherapy (RT). Medical records of 351 patients treated between 1994 and 2009 were retrospectively analyzed. Adjuvant RT was in the form of vaginal cuff brachytherapy (BRT) in patients with uterine confined disease and risk factors, whereas high-risk patients received risk-adapted external pelvic RT. The median follow-up time was 55 months (range, 2.5-133 months). Five-year overall (OS) and disease-free survival (DFS) for the entire group was 83 and 88%, respectively. Stage migration was observed in 188 (54%) patients. Stage migration generally did not cause any significant effect in OS and DFS rates. However, 5-year OS and DFS for stage I patients with positive peritoneal cytology was significantly lower than the other patients with negative cytology in FIGO 2009 system. The survival curves overlapped for stage IA, IB and II in the new staging system. On the other hand, the division of stage IIIC as IIIC1 and IIIC2 significantly affected the prognosis. Patients with stage IIIC2 tumor had 40% OS and 48% DFS rates compared to 69 and 66% in stage IIIC1 patients (p=0.002). The major improvement of FIGO 2009 seems to be the subclassification of stage IIIC disease into IIIC1 and IIIC2. The positivity of peritoneal cytology per se seems to have an influence in prognosis in our cohort. To withdraw the positive cytology from staging may mislead the prognosis estimation in these patients and lead to undertreatment.

Metastatic malignant melanoma of the uterine cervix: first diagnosed on liquid-based cytology.

Malignant melanomas of the female genital tract are uncommon lesions. The first case of vulvar melanomas with a subsequent malignant melanoma of the cervix diagnosed based on liquid-based cytology without evidence of gross pathology is described.

Evaluation of radiotherapy response of cervical carcinoma with gray scale and color Doppler ultrasonography: resistive index correlation with magnetic resonance findings.

PURPOSE: To investigate the role of the resistive index measured with transvaginal color Doppler ultrasonography (TVCDUS) for assessing the radiotherapy response of cervical carcinoma and to compare it with magnetic resonance findings. MATERIALS AND METHODS: A total of 13 patients with advanced stage cervical carcinoma (>IIA) underwent magnetic resonance imaging (MRI) and TVCDUS exams 6 months prior to and 6 months after radiotherapy. Pre- and post-treatment resistive indices obtained from the central and peripheral zones of the tumor were compared. These values were also compared with MRI findings and resistive indices obtained from the control group. RESULTS: Tumoral masses could be visualized in all patients with B-mode TVCDUS prior to the treatment. Resistive indices before and after treatment were 0.20-0.82 (mean: 0.52+/-0.15), and 0.70-0.99 (mean: 0.81+/-0.14), respectively. Eleven out of 13 patients responded to the treatment completely and no mass was detected in MRI and TVCDUS. Investigations were performed in areas with flow within the tumor-free cervix. A residual mass was noted in 2 patients with MRI and TVCDUS. There was a statistically significant difference between complete response to the treatment and increased resistive indices (P=0.001). In 2 patients with residual masses, no increase in resistive indices was detected. The mean resistive index of the control group was 0.65+/-13 and the difference was statistically significant compared to the resistive indices of the patients prior to the treatment. CONCLUSION: Since there was a significant correlation between the MRI findings and resistive indices, the spectral parameters obtained with TVCDUS were a good alternative to such an expensive modality as MRI in the evaluation of the response of cervical cancer to the treatment.

Analysis of metastatic ovarian tumors from extragenital primary sites.

AIMS AND BACKGROUND: The aim of this study was to evaluate patients with metastatic ovarian tumors from extragenital primary sites. METHODS: The medical records of 75 patients were reviewed retrospectively for age at diagnosis, presenting symptoms, preoperative tumor marker levels, preoperative diagnostic workup, operative technique, intraoperative evaluation, frozen-section and pathology results, laterality of metastasis, and primary tumor site. The specific impact of metastasis from colorectal and gastric primary sites on laterality, gross features and dimensions of ovarian mass, volume of ascites and tumor marker levels was investigated. RESULTS: Primary sites were stomach (37.3%), colorectal region (28%), lymphoma (12%), breast (6.7%), biliary system (2.7%), appendix (1.3%) and small intestine (1.3%). It was not possible to identify the primary tumor site in 8 (10.7%) patients. Bilateral metastasis was found in 86.4% patients; 42.7% of the metastatic ovarian tumors were Krukenberg tumors; 50.7% of the ovarian masses were solid. Frozen section was confirmed by postoperative pathological results in 98% of the patients. The mean preoperative serum levels of tumor markers were 298.7 U/mL, 178 U/mL and 113.3 U/mL for CA 125, CA 19-9 and CA 15-3, respectively. CA 125 levels were above 35 U/mL in 81.3% of the patients. The presence of ascites was more frequent in ovarian tumors originating from colorectal and gastric primaries. CONCLUSIONS: Surgery is essential for the diagnosis of the primary tumor and necessary for relief of symptoms. The identification of the primary site is required to plan adequate treatment.

Efficacy of transvaginal contrast-enhanced MRI in the early staging of cervical carcinoma.

The objective of this study was to evaluate the efficacy of transvaginal contrast for local staging of cervical carcinoma. Fifty patients diagnosed with cervical carcinoma prospectively underwent magnetic resonance (MR) imaging before and after vaginal opacification (VO) with a mixture of 25 ml saline and 25 ml barium. T2-weighted (T2W) TSE images in axial and sagittal planes were compared before and after vaginal opacification. Dynamic T1W images in sagittal and fat-suppressed T1W images in transverse planes were also evaluated after intravenous contrast administration. Involvement of vaginal wall, lumen, and fornices; parametrium; rectum; and bladder were noted. Changes in local tumor staging and in treatment planning were also assessed after vaginal opacification. MR results were later compared with surgical pathological findings. Twenty-eight patients who went through surgical staging were included in the study. VO did not change any of the MR interpretations in 14 patients (50%). Correct staging was achieved with T2W TSE images with and without VO (in sagittal and transverse planes) in 78.5% and 50% of the patients, respectively. VO correctly lowered staging in seven and increased it in three patients compared with sagittal standard T2W images. Treatment planning was also changed in four (14%) of these patients. When overall accuracy of MR staging to indicate the appropriate treatment was evaluated, patients would have received the proper treatment in 90% and 79% of the cases when only T2W sagittal images with and without VO were evaluated, respectively. Dynamic gradient-echo images in sagittal planes and postcontrast T1W images in transverse planes evaluated with T2W series after VO, accomplished correct staging in 23 (82%) of the patients. MRI staging in early cervical cancer may be difficult and overestimated, especially if the tumor is slightly extended into the proximal vagina. Use of vaginal contrast medium is an easy, well-tolerated, and effective method to better delineate the borders of the tumor. It increases the specificity and accuracy of MR staging by showing the exact relation of the tumor with the vaginal wall and beyond.

Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer.

OBJECTIVE: To evaluate the significance of preoperative platelet counts in advanced epithelial ovarian cancer with respect to second-look laparotomy results and disease progression. METHODS: We prospectively evaluated 37 consecutive patients with advanced epithelial ovarian cancer who underwent primary surgical treatment. In addition to platelet counts, all patients were evaluated with respect to age, gravida, parity, and stage and grade of tumor. Thirty-six patients had stage III, and 1 patient had stage IV disease. Optimal debulking (diameter of residual tumor, less than 1 cm) was performed in all patients who subsequently received adjuvant chemotherapy (platin-paclitaxel). According to second-look laparotomy and follow-up results patients were divided into 2 groups. The first group had negative second-look laparotomy or no evidence of disease during follow-up (n = 20), and the second group had positive second-look laparotomy or progressive disease (n = 17). Sensitivity and specificity values were calculated for different cutoff values of platelet counts with receiver operating characteristic curve analysis. RESULTS: Age, gravida, and parity were not significantly different compared with controls (P >.05). Mean platelet counts were 371 x 109/L and 446 x 109/L in the first and second groups, respectively (P =.03). Different cutoff values of platelet counts for the diagnosis of thrombocytosis were evaluated. A cutoff value of 380 x 109/L had sensitivity 77% and specificity 60% for recurrence, whereas a cutoff value of 400 x 109/L had sensitivity 59% and specificity 65%. Area under the curve (+/- standard error) was 0.72 +/- 0.08 (P =.026). CONCLUSION: In patients with progressive disease and positive second-look laparotomy, preoperative platelet counts were significantly higher compared with patients with no evidence of disease on follow-up.

Results of postoperative radiotherapy in the treatment of 29 uterine sarcoma patients.

AIMS AND BACKGROUND: The objective of this study was to evaluate the results of surgery combined with postoperative radiotherapy (RT) in patients with uterine sarcoma in order to describe the patterns of relapse and to define prognostic factors. METHODS: We report on 29 patients with uterine sarcoma (US) treated from 1980 to 1995; 18 patients with primary tumors were treated with surgery and adjuvant irradiation, while 11 patients with local recurrences (LR) after previous surgical resection received only radiotherapy. We evaluated the influence of stage, histology, grade, menopausal status, total radiation dose and brachytherapy on survival. Histological diagnosis was leiomyosarcoma in 13 patients (44.8%), endometrial stromal sarcoma in 10 patients (34.5%), and mixed mesodermal tumors in six patients (20.7%). Fifteen patients presented with stage I-II disease, three with stage III, and 11 with local recurrences. External pelvic RT was administered to all patients, in five patients combined with brachytherapy. The mean total dose was 54 Gy (SE 1.78). Univariate and multivariate analyses were carried out. RESULTS: Overall survival (OS) for the stage I-III group was 61.1% at two years and 33.3% at five years (median 29 months, SE 13.79). Disease-free survival (DFS) was 55.6% at two years and 33.3% at five years. Median DFS was 26 months (SE 14.85). In LR cases, median OS was only 10 months (SE 4.5). Multivariate analysis demonstrated that stage was the only prognostic factor after RT for US. CONCLUSIONS: These data suggest that postoperative and/or salvage RT has a questionable impact on disease-free and over-all survival because of the lack of homogeneity of stages in the series reported in the literature; it has, however, acceptable late side effects. Prospective multicenter trials including a statistically evaluable number of patients are necessary to further clarify the role of RT treatment programs for US.

Is frozen-section diagnosis a reliable guide in surgical treatment of stage I endometrial carcinoma?

Frozen-section diagnoses and paraffin-section diagnoses were compared in 154 patients in stage I endometrial adenocarcinoma. In 134 (87%) of the 154 patients (p < 0.001), a corresponding depth of myometrial invasion was found, and in 132 (85.7%) patients the same tumor grade was established (p < 0.001). Frozen-section diagnosis of stage I endometrial adenocarcinoma is reliable for estimation of the extent of disease and accurately identifies patients who require surgical staging.