Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Factors associated with the involvement of lymph nodes in low-grade serous ovarian cancer.

BACKGROUND AND OBJECTIVES: Evaluating nodal metastases in low-grade serous ovarian cancer (LGSOC) patients. METHODS: Women with LGSOC who had undergone primary cytoreductive surgery comprising systematic pelvic-paraaortic lymphadenectomy were included. Data were obtained retrospectively from 12 oncology centers. RESULTS: One hundred and forty-eight women with LGSOC who had undergone comprehensive surgical staging were included. Seventy-one (48.0%) patients had metastatic lymph nodes. Preoperative serum CA-125 levels of ≥170 U/ml (odds ratio [OR]: 3.84; 95% confidence interval [CI]: 1.22-12.07; p = 0.021) and presence of lymphovascular space invasion (LVSI) (OR: 13.72; 95% CI: 3.36-55.93; p < 0.001) were independent predictors of nodal metastasis in LGSOC. Sixty (40.5%) patients were classified to have apparently limited disease to the ovary/ovaries. Twenty (33.3%) of them were upstaged after surgical staging. Twelve (20.0%) had metastatic lymph nodes. Presence of LVSI (OR: 12.96; 95% CI: 1.14-146.43; p = 0.038) and preoperative serum CA-125 of ≥180 U/ml (OR: 7.19; 95% CI: 1.35-38.12; p = 0.02) were independent predictors of lymph node metastases in apparent Stage Ⅰ disease. CONCLUSIONS: Clinicians may consider to perform a reoperation comprising systematic lymphadenectomy in patients who had apparently limited disease to the ovary/ovaries and had not undergone lymphadenectomy initially. Reoperation may be considered particularly in patients whose preoperative serum CA-125 is ≥180 U/ml and/or whose pathological assessment reported the presence of LVSI.

Outcomes of the conservative management of the patients with endometrial intraepithelial neoplasia/endometrial cancer: Wait or treat!

Background/aim: The objective of the study was to evaluate the response, relapse, reproductive results and demographic features of the patients with endometrioid adenocancer (EAC) and endometrial intraepithelial neoplasia (EIN) who were treated with conservative treatment. This is the largest study when we consider the single center studies in this field. Materials and methods: In the current retrospective study, 38 patients (6 EAC, 31 EIN, 1 synchronous tumors of ovary and endometrium) were recruited. They were treated with progesterone products for their fertility desire and comorbidity. Reproductive results, response rates, and recurrence rates were calculated and survival analyses were performed. Results: Mean duration of the medical treatment was 10 months (range 2­60). Among the 32 patients with EIN, 28 (87.5%) had a response, 8 (25%) had a relapse and 4 (12.5%) had persistence. Among the 32 patients who expecting fertility, seven patients got pregnant (21.8%) with a total of five live births. The median follow-up was 40.5 months (range 3­180), and recurrence-free interval was 28.7 months (range 2­180). Conclusion: Fertility-sparing treatment of EAC and EIN is a feasible approach, and the eligible patients should be given a chance to get pregnant.

Patterns of diaphragm involvement in stage 3B/3C ovarian-tubal-peritoneal epithelial cancer patients and survival outcomes.

PURPOSE: Demonstrate survival outcomes of stage 3B/3C ovarian-tubal-peritoneal epithelial cancer patients who had metastases on diaphragm. METHODS: 141 patients who had undergone diaphragm surgery as a part of primary cytoreductive surgery procedures performed for stage 3B and 3C ovarian-tubal-peritoneal epithelial cancers were reviewed retrospectively. Patients who were administered neoadjuvant chemotherapy and patients who were suboptimally cytoreduced were not included to the study. RESULTS: Median follow-up time was 42 months. Median overall survival of the patients who underwent diaphragm full-thickness resection (n = 18) because of tumors infiltrating diaphragm muscle was 40 months. Median overall survival of the patients who did not have a transdiaphragmatic thoracotomy (n = 113) was 77 months. Patients who underwent a willful full-thickness diaphragm resection because of tumors invading diaphragm muscle had significantly shorter survival compared with patients who did not have a transdiaphragmatic thoracotomy (p = 0.033). Seven (38.9%) of the 18 patients who underwent diaphragm full-thickness resection developed a recurrence in thorax. Twelve (9.8%) of the remaining 123 patients developed a recurrence in thorax. Patients who underwent full-thickness diaphragm resection because of tumors infiltrating diaphragm muscle developed recurrence in the thorax more frequently (p = 0.001). CONCLUSIONS: Diaphragm muscle involvement is a predictor of thorax recurrences and worse survival outcomes in stage 3B and 3C ovarian-tubal-peritoneal epithelial cancers. Thus, this should be considered when selecting appropriate adjuvant treatment and route of administration (intravenous/intraperitoneal) in patients who had diaphragm implants infiltrating diaphragm muscle.

Pulmonary morbidity related to diaphragm surgery performed for gynecological cancers.

OBJECTIVE: To evaluate pulmonary morbidity related to diaphragm surgery performed for gynecological cancers and to identify the impact of transdiaphragmatic thoracotomy. MATERIALS AND METHODS: We reviewed clinical and pathologic data of 232 women who had undergone diaphragm surgery as a part of cytoreductive surgery procedures performed for gynecological cancers. RESULTS: Transdiaphragmatic thoracotomy occurred in 52 patients (22.4%). Rate of pulmonary complications among patients who had a transdiaphragmatic thoracotomy was higher compared with patients who did not have a transdiaphragmatic thoracotomy (40.4% vs 20.6%, p=0.004). Transdiaphragmatic thoracotomy [odds ratio (OR), 2.66; 95% confidence interval (CI), 1.20-5.92; p=0.016], colon resection (OR, 5.21; 95% CI, 2.34-11.63; p<0.001), ileostomy (OR, 19.61; 95% CI, 1.64-250.0; p=0.019), and any extra-pulmonary complication occurrence (OR, 2.35; 95% CI, 1.13-4.88; p=0.023) were identified as independent predictors of pulmonary morbidity. Patients with transdiaphragmatic thoracotomy developed pleural effusion, pleural effusion necessitating drainage, pneumothorax, pneumonitis, and atelectasis more frequently compared with patients who did not have transdiaphragmatic thoracotomy. Rate of admission to postoperative intensive care of patients with transdiaphragmatic thoracotomy (30.8%) was significantly higher than that of patients without transdiaphragmatic thoracotomy (12.2%) (p=0.001). CONCLUSION: Transdiaphragmatic thoracotomy is an independent predictor of pulmonary morbidity among patients who underwent diaphragm surgery. Avoiding accidental transdiaphragmatic thoracotomies with maximal attention and performing full-thickness resection procedures with alternative surgical techniques preventing a thoracotomy may help decrease pulmonary morbidity rates and postoperative care costs.

Does lymph node ratio have any prognostic significance in maximally cytoreduced node-positive low-grade serous ovarian carcinoma?

PURPOSE: To determine the prognostic impact of the lymph node ratio (LNR) in node-positive low-grade serous ovarian cancer (LGSOC). METHODS: We retrospectively reviewed women with LGSOC who had undergone maximal cytoreduction followed by standard chemotherapy in 11 centers from Turkey during a study period of 20 years. Sixty two women with node-positive LGSOC were identified. LNR was defined as the number of metastatic lymph nodes (LNs) divided by the number of total LNs removed. We grouped patients pursuant to the LNR as LNR ≤ 0.09 and LNR > 0.09. The prognostic value of LNR was investigated by employing the univariate log-rank test and multivariate Cox-regression model. RESULTS: With a median follow-up of 45 months, the 5-year progression-free survival (PFS) rates were 61.7% for women with LNR ≤ 0.09 and 32.0% for those with LNR > 0.09 (p = 0.046) whereas, the 5-year overall survival (OS) rates were 72.8% for LNR ≤ 0.09 and 54.7% for LNR > 0.09 (p = 0.043). On multivariate analyses, lymphovascular space invasion (LVSI) (Hazard Ratio [HR] 4.18, 95% confidence interval [CI] 1.88-9.27; p < 0.001), omental involvement (HR 3.48, 95% CI 1.36-8.84; p = 0.009) and LNR > 0.09 (HR 3.51, 95% CI 1.54-8.03; p = 0.003) were adverse prognostic factors for PFS. Additionally, LVSI (HR 6.56, 95% CI 2.33-18.41; p < 0.001), omental involvement (HR 6.34, 95% CI 1.86-21.57; p = 0.003) and LNR > 0.09 (HR 7.20, 95% CI 2.33-22.26; p = 0.001) were independent prognostic factors for decreased OS. CONCLUSION: LNR > 0.09 seems to be an independent prognosticator for decreased survival outcomes in LGSOC patients who received maximal cytoreduction followed by standard adjuvant chemotherapy.

Complementary surgery for cervical cancer patients inadequately treated with extrafacial hysterectomy.

OBJECTIVE: To evaluate surgical outcomes and survival outcomes of cervical cancer patients who underwent complementary surgery after an extrafacial hysterectomy METHODS: Patients with cervical cancer, who underwent extrafacial hysterectomy initially and thereafter underwent complementary surgery were reviewed retrospectively. Complementary surgery consisted of radical parametrectomy, proximal vaginectomy and pelvic lymphadenectomy. RESULTS: Twenty patients were evaluated. Histopathologic subtype was squamous cell carcinoma in twelve patients, adenocarcinoma in six patients and adenosquamous carcinoma in two patients. Route of surgery was laparotomy in 19 patients and laparoscopy in one patient. Two patients were staged as stage 1A2, nine were staged as stage 1B1, four were staged as stage 1B2, one was staged as stage 2A1, one was staged as stage 2B and three were staged as stage 3C1. The median tumor size was 16.5 (Range, 4-40) mm. Grade ≥ 3 complications related to surgery occured in 8 (40%) patients. Four of them were managed intraoperatively and recovered problem free. Remaining four (20%) needed reoperation. Pathology reports revealed involvement of parametrium in one (5%) patient, involvement of the proximal vagina in one (5%) patient, matastasis to pelvic lymph nodes in 3 (15%) patients. Five (25%) patients received adjuvant radiotherapy. Consequently, 5-year and 10-year cumulative survival was calculated as 94%. CONCLUSION: Complementary surgery and radiotherapy show similar oncologic outcomes in patients with early-stage cervical cancer who had undergone simple hysterectomy initially. Complementary surgery is associated with slightly higher rate of morbidity compared with radiotherapy, however significant proportion of complications can be noticed and repaired intraoperatively.

Can we predict surgical margin positivity while performing cervical excisional procedures?

We designed this study to evaluate any factors associated with positive surgical margin in conisation specimens and to determine the optimal cone size. The medical records of patients who had undergone a loop electrosurgical excision procedure (LEEP), cold-knife conisation (CKC) and needle excision of the transformation zone (NETZ) procedure were reviewed retrospectively. Two hundred and sixty eight women fulfilled the inclusion criteria. Univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage (ECC) material and in two or more ectocervical quadrants' and 'managing with LEEP' were significant predictors of surgical margin positivity. Nulliparous patients showed significantly lower rate of surgical margin positivity. 'Postmenopause', 'previous colposcopic examination revealing HSIL in ECC material and in two or more ectocervical quadrants' and 'HSIL on smear' were identified as independent predictors of surgical margin positivity according to multivariate analyses.IMPACT STATEMENTWhat is already known on this subject? Previous studies demonstrated 'menopause', 'Age ≥50', 'managing with LEEP', 'disease involving >2/3 of cervix at visual inspection', 'training level of the surgeon', 'cytology squamous cell carcinoma' and 'mean cone height' as factors associated with positive surgical margin in conisation specimens.What do the results of this study add? In our study, univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'managing with LEEP' were associated with surgical margin positivity. On the other hand, nulliparous women showed significantly lower rate of surgical margin positivity compared with parous women. Multivariate analyses showed that 'postmenopause', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'HSIL on smear' were independent predictors of surgical margin positivity in conisation specimens.What are the implications of these findings for clinical practice and/or further research? We can predict high-risk patients with regard to surgical margin positivity. Prediction of high-risk patients and management with a tailored approach may help minimise surgical margin positivity rates.

High-grade uterine corpus-confined endometrial cancer with lymphadenectomy: does adjuvant therapy improve survival?

OBJECTIVE: To evaluate the necessity of adjuvant therapy and other prognostic factors in high-grade uterine corpus-confined endometrial cancer (EC) with lymphadenectomy performed. MATERIALS AND METHODS: This study included 120 patients who had endometrioid-type grade 3, serous-type, clear cell-type, and undifferentiated-type EC and underwent lymphadenectomy. RESULTS: Patients with high-grade uterine corpus-confined EC who underwent lymphadenectomy were evaluated. The modality of adjuvant therapy performed was not a predictor for the site of recurrence. The loco-regional recurrence rate decreased from 9.5% to 3.8% in patients who received radiotherapy. However, this difference was not statistically significant (p=0.206). In addition, performing adjuvant chemotherapy did not alter the risk of extrapelvic recurrence. Only International Federation of Gynecology and Obstetrics 2009 stage was significant in the univariate analysis. On the other hand, age, tumor type, number of removed lymph nodes, presence of myometrial and lymphovascular space invasion, tumor size and adjuvant therapy modality were not related with disease-free survival. CONCLUSION: Performing adjuvant therapy and therapy modality does not improve oncologic outcomes in intermediate and high-risk patients. However, radiotherapy reduced the risk of local recurrence by more than 50%. Vaginal brachytherapy was efficient as external beam radiotherapy. Therefore, vaginal brachytherapy should be used for these patients in order to reduce loco-regional recurrence even if it is not reported to be effective on disease-free survival.

Does tumor size have prognostic value in patients undergoing lymphadenectomy in endometrioid-type endometrial cancer confined to the uterine corpus?

Background/aim: We aimed to define the effect of tumor size on recurrence and survival rates in patients with stage I­II endometrioid-type endometrial cancer. Materials and methods: A total of 550 patients who had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic-paraaortic lymphadenectomy were included. Patients with extrauterine spread, sarcomatous components, or synchronized tumor and those who did not undergo lymphadenectomy or did not have data on tumor size were excluded. Results: The median tumor size was 35 mm (range: 3­335 mm). According to the 2009 International Federation of Obstetrics and Gynecology (FIGO) criteria, 245 cases were defined as stage IA, 271 as stage IB, and 34 as stage II. The 5-year disease-free survival (DFS) rate was 92% and the 5-year disease-specific survival (DSS) rate was 99%. The effects of prognostic factors on DFS were evaluated. Older age, stage II disease, deep myometrial invasion, and receiving adjuvant radiotherapy were associated with decreased DFS. There was no statistically significant association between tumor size and DFS. The 5-year DFS for patients with a tumor diameter of <35 mm, which was the median tumor size of the entire group, was 94%, while it was 89% for patients having a tumor diameter of >35 mm (P = 0.128). Conclusion: Tumor size was not a risk factor predicting recurrence in patients with stage I or II endometrioid-type endometrial cancer who had lymphadenectomy.

Metastasis patterns of the spleen and association with survival outcomes in advanced ovarian-tubal-peritoneal epithelial cancer.

PURPOSE: To evaluate the significance of parenchymal, hilar and capsular involvement of the spleen with regard to survival. METHODS: All patients who underwent primary cytoreductive surgery for advanced ovarian-tubal-peritoneal (OTP) epithelial cancer were reviewed retrospectively. Stage 3C patients who had an upper abdomen involvement and who were optimally debulked were included. Patients who had abdomen-confined disease, but were upstaged to stage 4B due to splenic parenchymal metastases were also included. RESULTS: Seventy four patients eligible with the inclusion criteria who underwent splenectomy and 69 patients who did not undergo splenectomy were included. The median follow-up time was 39.1 months. The median overall survival of the study group was 61.4 months. Patients who underwent splenectomy were grouped according to the involved site of the spleen: parenchyma subgroup, hilus subgroup, capsule subgroup and benign subgroup. The median overall survival of patients in the hilus subgroup was 41.1 months. The median overall survival of patients who were not in the hilus subgroup was 65.5 months. Patients in the hilus subgroup showed significantly shorter survival (p = 0.035). Hilus subgroup was associated with a statistically significant increase in mortality risk (hazard ratio 1.971; 95% confidence interval 1.1-3.531). CONCLUSIONS: Splenic hilus involvement predicts poorer survival outcomes among stage 3C epithelial OTP cancer patients with disease expansion to upper abdomen. According to current study and many published studies, hilar involvement had a higher incidence rate compared to parenchymal involvement. Thus, hilar involvement would be a beneficial clinical predictor of survival for larger number of patients.

Silicon and Iron as Resource-Efficient Anode Materials for Ambient-Temperature Metal-Air Batteries: A Review.

Metal-air batteries provide a most promising battery technology given their outstanding potential energy densities, which are desirable for both stationary and mobile applications in a "beyond lithium-ion" battery market. Silicon- and iron-air batteries underwent less research and development compared to lithium- and zinc-air batteries. Nevertheless, in the recent past, the two also-ran battery systems made considerable progress and attracted rising research interest due to the excellent resource-efficiency of silicon and iron. Silicon and iron are among the top five of the most abundant elements in the Earth's crust, which ensures almost infinite material supply of the anode materials, even for large scale applications. Furthermore, primary silicon-air batteries are set to provide one of the highest energy densities among all types of batteries, while iron-air batteries are frequently considered as a highly rechargeable system with decent performance characteristics. Considering fundamental aspects for the anode materials, i.e., the metal electrodes, in this review we will first outline the challenges, which explicitly apply to silicon- and iron-air batteries and prevented them from a broad implementation so far. Afterwards, we provide an extensive literature survey regarding state-of-the-art experimental approaches, which are set to resolve the aforementioned challenges and might enable the introduction of silicon- and iron-air batteries into the battery market in the future.

Sertoli-Leydig cell tumor of the ovary: Analysis of a single institution database and review of the literature.

AIM: To evaluate the clinical characteristics and outcome of ovarian Sertoli-Leydig cell tumors (SLCTs) managed at a single institution. METHODS: The hospital records of 17 patients with the diagnosis of ovarian SLCT between 1994 and 2018 were reviewed retrospectively. RESULTS: The median age of the patients was 30 years (range, 18-67 years). All the patients had unilateral tumors. All of the 17 were stage 1 tumors. Two (11.8%) patients were stage 1C1 and two (11.8%) patients were stage 1C2. Thirteen (76.5%) patients were stage 1A. Three (17.6%) of the tumors were well differentiated, 11 (64.7%) were intermediately differentiated, 1 (5.9%) was poorly differentiated, and the degree of the differentiation was not identified for 2 (11.8%) patients. One showed retiform pattern and one had heterologous elements at the histopathologic evaluation. Among the 17 patients, we identified structural/vascular renal and ureteral anomalies in 3 (17.6%) patients. Eight patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, seven underwent unilateral salpingo-oophorectomy or oophorectomy and two underwent cystectomy with or without additional surgical staging procedures. Four patients received adjuvant chemotherapy. All the 17 patients were alive and free of disease for 1-287 months after the diagnosis. Median follow-up time was 78 months. None of the patients recurred. CONCLUSION: Sertoli-Leydig cell tumors are rare ovarian malignancies with low recurrence rates and have a favorable outcome compared to malignant epithelial tumors of the ovary. Main treatment is surgical resection and it is appropriate to prefer fertility sparing conservative surgeries for young patients.

Prognostic factors and oncological outcomes of ovarian yolk sac tumors: a retrospective multicentric analysis of 99 cases.

PURPOSE: To investigate the clinico-pathological prognostic factors and treatment outcomes in patients with ovarian yolk sac tumors (YST). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian YST who underwent surgery between 2000 and 2017 at seven Gynecologic Oncology Centers in Turkey. RESULTS: The study group consisted of 99 consecutive patients with a mean age of 23.9 years. While 52 patients had early stage (stage I-II) disease, the remaining 47 patients had advanced stage (stage III-IV) disease. The uterus was preserved in 74 (74.8%) of the cases. The absence of gross residual disease following surgery was achieved in 76.8% of the cases. Of the 54 patients with lymph node dissection (LND), lymph node metastasis was detected in 10 (18.5%) patients. Of the 99 patients, only 3 patients did not receive adjuvant therapy, and most of the patients (91.9%) received BEP (bleomycin, etoposide, cisplatin) chemotherapy. Disease recurred in 21 (21.2%) patients. The 5-year disease-free survival (DFS) and overall survival (OS) in the entire cohort were 79.2% and 81.3%, respectively. In multivariate analysis, only residual disease following initial surgery was found to be significantly associated with DFS and OS in patients with ovarian YST (p = 0.026 and p = 0.001, respectively). CONCLUSIONS: Our results demonstrate the significance of achieving no visible residual disease in patients with ovarian YST. Fertility-sparing approach for patients with no visible residual disease affected neither DFS nor OS. Although high lymphatic involvement rate was detected, the benefit of LND could not be demonstrated.

Uncommon borderline ovarian tumours: A clinicopathologic study of seventeen patients

Objective: To evaluate uncommon types of borderline ovarian tumors (BOT) and define the clinical, surgical, and pathologic features. Material and Methods: Seventeen patients who were treated in our hospital between 1990 and 2017 were identified. Patients' data were collected from the gynecologic oncology clinic electronic database, patients' files, and pathology reports. Conservative surgery was defined as preservation of the uterus and at least part of one ovary. Results: The mean age was 47 (range, 22-70) years. Based on histopathologic tumor type, there was mixed tumor in five (29.4%) patients, endometrioid-type in nine (52.9%), seromusinous-type in two (11.8%), and Brenner-type in one (5.9%). Conservative surgery was performed in 4 patients. Two patients with endometrioid BOT had synchronous endometrial pathology, including one (11%) patient with endometrial cancer, one (11%) with endometrial hyperplasia without atypia, and 3 (33%) patients had endometriosis. The median follow-up was 19 (range, 1-137) months. No recurrence was observed during the follow-up period. Conclusion: In our small volume case series, it could be said that non-serous/non-mucinous BOT has excellent prognosis. However, endometrial pathology should be checked in endometrioid type.