Prognostic impact of p16 and p53 gene expressions in stage 1a epithelial ovarian cancer

Objective@#Epithelial ovarian cancer (EOC) is rarely detected at stage 1a. Most of the patients have a good prognosis and there are limited factors that affect their survival. In the present study, we evaluated the p16 and p53 gene expressions of stage 1a EOC patients. Prognostic effects of these gene expressions, as well as those of other factors on short term survival were analyzed. @*Methods@#Our study included 29 patients. The specimens of the ovary with cancer were stained for p16 and p53. Gene expressions and other prognostic factors were evaluated. @*Results@#The median age of the patients was 51 years (27–84). The mean numbers of dissected pelvic and paraaortic lymph nodes were 27 and 12, respectively. The mean follow-up time was 33.7±18.9 months. During this period, recurrence occurred in two patients. One of the patients had grade 2 mucinous carcinoma and died of the disease at month 12 after the recurrence occurred at month 7. The second patient had clear cell carcinoma and recurrence occurred at month 34. p16 and p53 gene expressions or other factors were not associated with overall survival (OS) or disease-free survival in the short term. The lower p16 positivity rate in the non-clear cell group was found to be statistically significant (P=0.003). Both p53 and p16 positivity rates were higher in the high-grade carcinoma. @*Conclusion@#The levels of none of the common prognostic factors, including those of p16 and p53 gene expression, were associated with the progression-free survival or OS of stage 1a in the short term. Appropriate surgical staging and non-omission of subclinical metastases seem to be of central importance.

The prognostic value of lymph node ratio in stage IIIC cervical cancer patients triaged to primary treatment by radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy / 부인종양

Objective@#The aim of this study was to determine the prognostic value of lymph node ratio (LNR) in women with 2018 International Federation of Gynecology and Obstetrics stage IIIC cervical cancer. @*Methods@#In this retrospective dual-institutional study, a total of 185 node-positive cervical cancer patients who had undergone radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy were included. All of the patients received adjuvant chemoradiation after surgery. LNR was defined as the ratio of positive lymph nodes (LNs) to the total number of LNs removed. The patients were categorized into 2 groups according to LNR; LNR <0.05 and LNR ≥0.05. The prognostic value of LNR was evaluated with univariate log-rank tests and multivariate Cox regression models. @*Results@#A total of 138 patients (74.6%) had stage IIIC1 disease and 47 (25.4%) patients had stage IIIC2 disease. With a median follow-up period of 45.5 months (range 3–135 months), the 5-year disease-free survival (DFS) rate was 62.5% whereas the 5-year overall survival (OS) rate was 70.4% for the entire study population. The 5-year DFS rates for LNR <0.05 and LNR ≥0.05 were 78.2%, and 48.4%, respectively (p<0.001). Additionally, the 5-year OS rates for LNR <0.05 and LNR ≥0.05 were 80.6%, and 61.2%, respectively (p=0.007). On multivariate analysis, LNR ≥0.05 was associated with a worse DFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.15–3.90; p=0.015) and OS (HR=1.95; 95% CI=1.01–3.77; p=0.046) in women with stage IIIC cervical cancer. @*Conclusions@#LNR ≥0.05 seems to be an independent prognostic factor for decreased DFS and OS in stage IIIC cervical carcinoma.

Prognostic impact of p16 and p53 gene expressions in stage 1a epithelial ovarian cancer

Objective@#Epithelial ovarian cancer (EOC) is rarely detected at stage 1a. Most of the patients have a good prognosis and there are limited factors that affect their survival. In the present study, we evaluated the p16 and p53 gene expressions of stage 1a EOC patients. Prognostic effects of these gene expressions, as well as those of other factors on short term survival were analyzed. @*Methods@#Our study included 29 patients. The specimens of the ovary with cancer were stained for p16 and p53. Gene expressions and other prognostic factors were evaluated. @*Results@#The median age of the patients was 51 years (27–84). The mean numbers of dissected pelvic and paraaortic lymph nodes were 27 and 12, respectively. The mean follow-up time was 33.7±18.9 months. During this period, recurrence occurred in two patients. One of the patients had grade 2 mucinous carcinoma and died of the disease at month 12 after the recurrence occurred at month 7. The second patient had clear cell carcinoma and recurrence occurred at month 34. p16 and p53 gene expressions or other factors were not associated with overall survival (OS) or disease-free survival in the short term. The lower p16 positivity rate in the non-clear cell group was found to be statistically significant (P=0.003). Both p53 and p16 positivity rates were higher in the high-grade carcinoma. @*Conclusion@#The levels of none of the common prognostic factors, including those of p16 and p53 gene expression, were associated with the progression-free survival or OS of stage 1a in the short term. Appropriate surgical staging and non-omission of subclinical metastases seem to be of central importance.

Factors associated with surgical morbidity of primary debulking in epithelial ovarian cancer

The prognostic value of lymph node ratio in stage IIIC cervical cancer patients triaged to primary treatment by radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy / 부인종양

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

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.

Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study / 부인종양

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18–87), and the median duration of follow-up was 36 months (range, 1–120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42–5.18; p<0.001). CONCLUSION: LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients.

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

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.

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

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.

Prognostic factors and treatment outcomes in surgically-staged non-invasive uterine clear cell carcinoma: a Turkish Gynecologic Oncology Group study / 부인종양

OBJECTIVE: To assess the prognosis of surgically-staged non-invasive uterine clear cell carcinoma (UCCC), and to determine the role of adjuvant therapy. METHODS: A multicenter, retrospective department database review was performed to identify patients with UCCC who underwent surgical treatment between 1997 and 2016 at 8 Gynecologic Oncology Centers. Demographic, clinicopathological, and survival data were collected. RESULTS: A total of 232 women with UCCC were identified. Of these, 53 (22.8%) had surgically-staged non-invasive UCCC. Twelve patients (22.6%) were upstaged at surgical assessment, including a 5.6% rate of lymphatic dissemination (3/53). Of those, 1 had stage IIIA, 1 had stage IIIC1, 1 had stage IIIC2, and 9 had stage IVB disease. Of the 9 women with stage IVB disease, 5 had isolated omental involvement indicating omentum as the most common metastatic site. UCCC limited only to the endometrium with no extra-uterine disease was confirmed in 41 women (73.3%) after surgical staging. Of those, 13 women (32%) were observed without adjuvant treatment whereas 28 patients (68%) underwent adjuvant therapy. The 5-year disease-free survival rates for patients with and without adjuvant treatment were 100.0% vs. 74.1%, respectively (p=0.060). CONCLUSION: Extra-uterine disease may occur in the absence of myometrial invasion (MMI), therefore comprehensive surgical staging including omentectomy should be the standard of care for women with UCCC regardless of the depth of MMI. Larger cohorts are needed in order to clarify the necessity of adjuvant treatment for women with UCCC truly confined to the endometrium.

Comparison of three different risk-stratification models for predicting lymph node involvement in endometrioid endometrial cancer clinically confined to the uterus / 부인종양

OBJECTIVE: To compare the clinical validity of the Gynecologic Oncology Group-99 (GOG-99), the Mayo-modified and the European Society for Medical Oncology (ESMO)-modified criteria for predicting lymph node (LN) involvement in women with endometrioid endometrial cancer (EC) clinically confined to the uterus. METHODS: A total of 625 consecutive women who underwent comprehensive surgical staging for endometrioid EC clinically confined to the uterus were divided into low- and high-risk groups according to the GOG-99, the Mayo-modified, and the ESMO-modified criteria. Lymphovascular space invasion is the cornerstone of risk stratification according to the ESMO-modified criteria. These 3 risk stratification models were compared in terms of predicting LN positivity. RESULTS: Systematic LN dissection was achieved in all patients included in the study. LN involvement was detected in 70 (11.2%) patients. LN involvement was correctly estimated in 51 of 70 LN-positive patients according to the GOG-99 criteria (positive likelihood ratio [LR+], 3.3; negative likelihood ratio [LR−], 0.4), 64 of 70 LN-positive patients according to the ESMO-modified criteria (LR+, 2.5; LR−, 0.13) and 69 of the 70 LN-positive patients according to the Mayo-modified criteria (LR+, 2.2; LR−, 0.03). The area under curve of the Mayo-modified, the GOG-99 and the ESMO-modified criteria was 0.763, 0.753, and 0.780, respectively. CONCLUSION: The ESMO-modified classification seems to be the risk-stratification model that most accurately predicts LN involvement in endometrioid EC clinically confined to the uterus. However, the Mayo-modified classification may be an alternative model to achieve a precise balance between the desire to prevent over-treatment and the ability to diagnose LN involvement.

Transobturator Tape Operation Is More Effective in Premenopausal Women than in Postmenopausal Women with Stress Incontinence

PURPOSE: Midurethral synthetic slings for female stress urinary incontinence are minimally invasive polypropylene mesh tapes that are inserted under the midurethra with trocars. In the past decade, this new technology has become the most commonly performed procedure for female stress urinary incontinence, replacing the traditional open procedures. However, its effectiveness in pre- and postmenopausal women has not previously been compared. MATERIALS AND METHODS: We assessed the clinical outcome of the transobturator tape (TOT) procedure in premenopausal (n=45) and postmenopausal (n=49) women by means of self-report and the Urinary Distress Inventory 6 (UDI-6) questionnaire. RESULTS: The mean age of the pre- and postmenopausal women was 44 and 60 years, respectively. Mean parity was 2.4 and 3, respectively. There were no significant differences with respect to mean operation time, duration of hospitalization, or intraoperative and postoperative complications. However, premenopausal women were more satisfied with the operation than were postmenopausal women (p=0.014). Also, UDI-6 scores were significantly better in premenopausal women (p=0.027). CONCLUSIONS: The TOT operation appeared to be more effective in premenopausal women with stress urinary incontinence. However, further studies with larger sample sizes are needed to confirm our results.

Prognostic factors in adult granulosa cell tumors of the ovary: a retrospective analysis of 80 cases / 부인종양

OBJECTIVE: Ovarian granulosa cell tumors are rare malignancies with a relatively favorable prognosis. However, patients still suffer from disease-related mortality. Therefore, the prognostic factors should be clarified. The purpose of this study was to investigate the clinical and pathologic characteristics related with disease recurrence and mortality in adult type ovarian granulosa cell tumors. METHODS: Eighty surgically staged patients with granulosa cell ovarian tumor treated at the Hacettepe University Hospital between 1982 and 2006 were retrospectively reviewed. Clinical and pathological characteristics were analyzed. RESULTS: Granulosa cell ovarian tumors accounted for 4.3% of malignant ovarian neoplasms. Mean age was 47.6 years. The most common presenting symptom was abnormal uterine bleeding (53.7%). Endometrial pathology was detected in 51.2% of patients preoperatively. Seventy percent of patients were diagnosed at stage I, and 53.8% of patients received adjuvant treatment. Mean follow-up was 67.5 months. Overall 5-year and 10-year survival was 91% and 86%, respectively. Mean survival was 147.1 months. Recurrence rate was 11.2%. In univariate analysis, advanced stage, advanced age, residual disease after surgery, and need for adjuvant treatment were associated with disease-related mortality and advanced stage disease and absence of initial staging surgery were associated with disease recurrence. However, in multivariate analysis, only initial stage was found to be a significant prognostic factor. CONCLUSION: Initial stage seems to be the single most important prognostic factor in ovarian granulosa cell tumors. Therefore, a comprehensive staging surgery should be attempted to document the real extent of disease and to estimate the oncologic outcome more accurately.