The Cukurova score in the prediction of primary cytoreduction in ovarian cancer.

OBJECTIVE: Primary debulking surgery has been the preferred surgical route and is still considered a quality indicator for advanced ovarian cancer surgery. However, a significant number of patients are not amenable to upfront surgery. Neoadjuvant chemotherapy and interval debulking surgery may be the most suitable approach for this group. This study aimed to evaluate a novel score for prediction of the cytoreduction results at primary debulking surgery for ovarian cancer patients. METHODS: This observational prospective study was conducted at a tertiary gynecologic oncology center between December 2020 and August 2022. Presumed primary stage III-IV epithelial ovarian carcinoma cases were included. Borderline tumors, and metastatic or non-epithelial ovarian malignancies, were excluded. Based on imaging findings, points were assigned to each anticipated surgical procedure required for complete cytoreduction. The sum of these points was multiplied by the patient's Eastern Cooperative Oncology Group (ECOG) score, and thus, the Cukurova-clinic score was established. Furthermore, the required surgical procedures based on laparoscopic evaluation were recorded, and the score was readjusted and calculated to obtain the Cukurova score. RESULTS: One hundred and fourteen patients were included in the study. Primary debulking surgery was performed in 70% of cases. Among them, complete cytoreduction (Cukurova score ≤12) was obtained in 97.3% of cases. Complete cytoreduction was not achieved in cases with Cukurova score >12. The odds ratio of 90-day mortality was 13.4 for patients with Cukurova score >12, compared with those with Cukurova score ≤12. CONCLUSION: The Cukurova score is a model for classifying advanced ovarian cancer patients who may be candidates for primary debulking surgery.

A Rare Pathological Phenotype of Endometrioid Serous and Clear-Cell Ovarian Cancer with PIK3CA Mutations in Relation to The Excellent Response of Alpelisib.

Patients with metastatic ovarian cancer who develop resistance to standard therapy with or without platinum need to search for other therapeutic choices. Therefore, identifying genetic alterations and selecting an approach to treatment using precision medicine techniques are important. In a patient diagnosed with mixed-type ovarian cancer after surgery, adjuvant therapy was applied with a combination of carboplatin and taxane, but the disease recurred. Upon evaluation of the patient as having platinum-sensitive epithelial ovarian cancer (EOC), combination therapy with bevacizumab was initially successful. However, disease progression was again observed, and molecular analysis revealed the presence of an E545K mutation in the PIK3CA gene; therefore, a selective PI3K inhibitor, alpelisib, was used as a treatment under the compassionate-use protocol. The patient's complications improved after receiving the alpelisib medication. The patient has been in complete remission for over two years. This case serves as a rare example that confirms the utility of alpelisib in managing mixed-type ovarian cancer.

Prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer.

OBJECTIVES: Non-endometrioid endometrial cancers (non-EEC) have different management from endometrioid endometrial cancers. The purpose of this study was to investigate the prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer and discuss the current literature with the findings. MATERIAL AND METHODS: The study included two hundred-three patients with non-EEC who underwent surgical treatment and follow-up between January 1996 and December 2018 in a University Hospital Gynecologic Oncology Center. The patients were divided into three groups according to whether omentectomy was performed and the presence of omental metastasis. The patient's demographics, clinical characteristics such as stage, grade, histopathologic type, lymphovascular space invasion (LVSI), myometrial invasion, lymph node involvement, and survival outcomes were compared between the groups. RESULTS: The study included 203 patients. Twenty-five patients (12%) had omental metastases. LVSI was reported in 57.3%, 88.0%, and 43.2% of the non-omentectomy, no-omental metastasis, and omental metastatic groups, respectively (p = 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) rates according to the tumor grade, peritoneal cytology, and lymphadenectomy were also compared and were found to be statistically similar. The five-year OS rates were 70.6% for the group without omental metastases and 16.2% for the group with omental metastases, respectively (p = 0.001). In the group of omentectomy, the five-year DFS rates were 62.2% in cases without omental metastasis and 13.0% in cases with omental metastasis (p = 0.001). The five-year OS rates of 86.3% and DFS rates of 80.0% in the group without omentectomy. CONCLUSIONS: In non-endometrioid tumors, the survival rate was better in the group that did not undergo omentectomy. Based on these results, we can say that omentectomy may not be necessary for non-endometrioid tumors whose omentum is found to be normal in intraoperative visual examination.

Laparoscopic radical hysterectomy and total vaginectomy for vaginal malignant melanoma with cervical metastasis

The presented case is a 63-years-old multiparous woman admitted with the complaint of postmenopausal bleeding. On gynecologic examination multifocal lesions were detected, including 1 cm on lateral vaginal wall, 4 cm on posterior vaginal wall and 0.5 cm on the left lateral part of the cervix. Histopathology examination gave a diagnosis of epithelioid malignant melanoma. Consequently, laparoscopic radical hysterectomy and total vaginectomy with bilateral pelvic and inguinofemoral lymph node dissection were planned. On both sides, pararectal and paravesical spaces were created and the ureter was identified. Then, the vesicouterine and vesicovaginal spaces were developed. Uterine artery and superior vesical artery were coagulated, cut and the lateral parametrium was prepared. The left ureter was dissected and the ureteral tunnel was unroofed up to the bladder entrance. Subsequently, the anterolateral parametrium was transected. Then, the infundibulopelvic and sacrouterine ligaments were sealed and transected. At this time, the rectovaginal space was developed. Bilateral paracolpos were transected. The endopelvic fascia with the levator muscles were sealed and cut circumferentially. Anteriorly, the pubovesicocervical fascia was transected and the bladder was mobilized up to the uretrovesical junction. Thereafter, through a vaginal approach, the cervix and vagina were inverted by grasping the cervix with a tenaculum. An incision on the posterior vaginal wall at the introitus was made and the urogenital diaphragm was dissected to connect with the pelvic cavity. The vaginal entrance was cut circumferentially and the surgical specimen was extracted. In conclusion, laparoscopy can be considered as a feasible approach for radical hysterectomy and total vaginectomy in selected patients.

Predictability of lymph node involvement in uterus-confined endometrioid endometrial cancer by tumour size, pattern and location measured with transvaginal ultrasonography: can we save time?

We aimed to investigate whether transvaginal ultrasonography (TVUSG)-measured tumour size, pattern and location were significant predictors for lymph node metastasis in the uterus-confined endometrioid endometrial cancer (EEC) patients. A total of 213 patients with EEC were recruited and 73 of them were considered eligible and were analysed according to lymph node involvement. Tumour size, pattern and location measured by transvaginal ultrasound were recorded. Thereafter, patients were distributed according to their lymph node involvement and were compared with respect to these parameters. The patients' median age was 56 (27-80). Mean of the resected lymph nodes was 29.68 and 33.5 in lymph-node-negative and positive patients, respectively (p=.525). Tumour diameter was measured >2 cm on transvaginal ultrasound in 28 (48.3%) and 13 (86.7%) cases of the lymph node-negative and positive arms, respectively (p=.008). Transvaginal ultrasound revealed that 18 (31.0%) tumours in lymph node-negative and two (13.3%) in the node positive patients had polypoid pattern (p=.171). Seventeen (54.8%) tumours of the lymph node-negative group and three (42.9%) of the node positive group were determined in the lower uterine segment (p=.250). While tumour diameter measured with TVUSG was predictable for lymph node involvement in the uterus-confined EEC, its pattern and location were not.Impact StatementWhat is already known on this subject? In clinically early-stage endometrioid endometrial cancer (EEC), it has been recognised for decades that selective lymphadenectomy is a more acceptable strategy than the systematic lymphadenectomy, owing to the low rate of lymph node metastases in the patients. Preoperative imaging, frozen section and recently accepted lymph node concept are the prominent methods in designating appropriate candidates for lymphadenectomy. The measurement of tumour diameter or size obtained intraoperatively by frozen section assessment is one of the parameters used in MAYO criteria for selective lymphadenectomy in endometrial cancer patients.What do the results of this study add? In our study, tumour diameter measured with transvaginal ultrasonography was predictable for lymph node involvement in the uterus-confined EEC.What are the implications of these findings for clinical practice and/or further research? Transvaginal ultrasonography-measured tumour diameter can be considered in deciding to proceed with pelvic lymphadenectomy while waiting for the frozen section result. It should be remembered that this approach could be considered only in clinics using MAYO criteria for selective lymphadenectomy, and it needs to be confirmed with more prospective studies.

Cardiophrenic and costophrenic lymph node resection via subxiphoid approach only

When enlarged cardiophrenic lymph nodes (CPLN) are resected the impact on survival is still uncertain, but resection contributes to accurate staging and complete gross resection in advanced ovarian cancer. CPLN resection can be performed via video-assisted thoracic surgery or transabdominally through the subxiphoid or transdiaphragmatic routes. The subxiphoid approach is used to reach the prepericardiac nodes located in the anterior mediastinum. The transdiaphragmatic route is used to remove the costophrenic and supradiaphragmatic paracaval lymph nodes located in the middle and posterior mediastinum, respectively. However, the transdiaphragmatic approach necessitates diaphragm opening and, in most cases, liver mobilization. Costophrenic nodes can be resected through the subxiphoid route in appropriate patients without opening the diaphragm. Thus, the subxiphoid approach may be preferred to remove the costophrenic lymph nodes, in cases in whom diaphragm resection is not anticipated, and especially when the resection procedure is planned to include the prepericardiac nodes. In this video article, we present the method of resecting both prepericardiac and costophrenic lymph nodes using only the subxiphoid approach in a case of advanced ovarian cancer. The subxiphoid virtual space between the pericardium and diaphragm was developed. The observed and palpated CPLNs were dissected and excised from the prepericardiac and right latero-cardiac spaces. Thereafter, diaphragm peritoneum beneath the right costophrenic nodes was dissected. After identifying any enlarged costophrenic nodes by palpation, the sternal and costal diaphragmatic attachments were incised and the right latero-cardiac space was extended. When the single enlarged node was reached, it was grasped and pulled with curved-ring forceps and ultimately resected.

Survival outcomes of women with grade 3 endometrioid endometrial cancer: the impact of adjuvant treatment strategies.

AIM: This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). MATERIALS AND METHODS: The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1 cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. RESULTS: The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0-5.6; P = 0.016-OS; HR 3.2, 95% CI 1.6-6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. CONCLUSION: Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I-II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III-IV G3-EEC.

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.

Prognostic factors and survival outcomes of women with uterine leiomyosarcoma: A Turkish Uterine Sarcoma Group Study-003.

To assess the clinicopathological features, prognostic factors, and survival rates associated with uterine leiomyosarcoma (uLMS). Databases from 15 participating gynecological oncology centers in Turkey were searched retrospectively for women who had been treated for stage I-IV uLMS between 1996 and 2018. Of 302 consecutive women with uLMS, there were 234 patients with Federation of Gynecology and Obstetrics (FIGO) stage I disease and 68 with FIGO stage II-IV disease. All patients underwent total hysterectomy. Lymphadenectomy was performed in 161 (54.5%) cases. A total of 195 patients received adjuvant treatment. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 42% and 54%, respectively. Presence of lymphovascular space invasion (LVSI), higher degree of nuclear atypia, and absence of lymphadenectomy were negatively correlated with DFS, while LVSI, mitotic count, higher degree of nuclear atypia, FIGO stage II-IV disease, and suboptimal surgery significantly decreased OS. LVSI and higher degree of nuclear atypia appear to be prognostic indicators for uLMS. Lymphadenectomy seems to have a significant effect on DFS but not on OS.

High-grade endometrial stromal sarcoma versus undifferentiated uterine sarcoma: a Turkish uterine sarcoma group study-001.

OBJECTIVE: Prognostic factors associated with high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS) have not been distinctly determined due to the repetitive changes in the World Health Organization (WHO) classification. We aimed to compare clinicopathologic features and outcomes of patients with HGESS with those of patients with UUS. METHODS: A multi-institutional, retrospective, cohort study was conducted including 71 patients, who underwent surgery at 13 centers from 2008 to 2017. An experienced gynecopathologist from each institution re-evaluated the slides of their own cases according to the WHO2014 classification. Factors associated with refractory/progressive disease, recurrence or death were examined using logistic regression analyses. Kaplan-Meier method and log-rank test were used for survival comparisons. RESULTS: The median disease-free survival (DFS) for HGESS and UUS was 12 months and 6 months, respectively. While the median overall survival was not reached in HGESS group, it was 22 months in the UUS group. Kaplan-Meier analyses revealed that patients with UUS had a significantly poorer DFS than those with HGESS (p = 0.016), although OS did not differ between the groups (p = 0.135). Lymphovascular-space involvement (LVSI) was the sole significant factor associated with progression, recurrence or death for HGESS (Hazard ratio: 9.353, 95% confidence interval: 2.539-34.457, p = 0.001), whereas no significant independent factor was found for UUS. CONCLUSIONS: UUS has a more aggressive behavior than HGESS. While no significant predictor of prognosis was found for UUS, LVSI is the sole independent prognostic factor for HGESS, with patients 9.3 times more likely to experience refractory/progressive disease, recurrence or death.

Feasibility and rationale of a novel approach in advanced ovarian cancer surgery: Bat- shaped en-bloc total peritonectomy and total hysterectomy salpingo-oophorectomy with or without rectosigmoid resection (Sarta-Bat approach).

OBJECTIVE: To evaluate the feasibility of bat-shaped en-bloc total peritonectomy and total hysterectomy-salpingo-oophorectomy with or without rectosigmoid resection as a novel approach in advanced ovarian cancer surgery. METHODS: Advanced ovarian cancer patients with widespread peritoneal implants requiring total peritonectomy were the subject of the study. Thirteen cases were operated with Sarta-Bat approach between February 2019 and July 2020. Patients' clinical and surgical data were collected and statistically analyzed. RESULTS: Median age of the patients was 52 (40-65). Histopathology of the tumors were high-grade serous carcinoma in 12 (92.3%) and carcinosarcoma in one (7.7%) cases and all of them originated from the ovary. Eight (61.5%), two (15.4%) and three (23.1%) patients were stage 3c, 4a, and 4b, respectively. Upper abdomen was involved in all cases. Nine cases underwent primary cytoreductive and four cases interval cytoreductive surgery. Sarta-Bat approach was performed as en-bloc total peritonectomy, total hysterectomy bilateral salpingo-oophorectomy with rectosigmoid resection in three and without rectosigmoid resection in 10 cases. Final surgery resulted in complete cytoreduction (no macroscopic residual) in all cases, with acceptable grade 2-3 morbidity rates. CONCLUSION: Sarta-Bat approach is a feasible and convenient technique for cytoreductive surgery of advanced ovarian cancer with disseminated peritoneal metastases.

Management of gynecological cancers in the COVID-19 era: a survey from Turkey

Objective: This study aimed to investigate how gynecologic oncologists modified their patient management during Coronavirus disease-2019 (COVID-19) in Turkey. Material and Methods: An online survey was sent to gynecologic oncology specialists and fellows in Turkey. It included management questions about strategies for newly diagnosed or recurrent endometrial, cervical, ovarian and vulvar cancer during the pandemic. Participants were asked if treatment of these cancers can be delayed or not and, if yes, the duration of delay. Results: 32.9% of surgeons prescribed oral or intrauterine progesterone for early stage, low-grade endometrial cancer. Conversely, 65.7% and 45.7% of the most surgeons did not change their management for early stage high-grade and advanced stage endometrial cancers respectively, as they perform surgery. 58% and 67.1% of the surgeons continued to prefer standard surgical treatment for microinvasive and early stage cervical cancers, respectively. Radiotherapy was preferred administered with hypofractionated doses for locally advanced cervical cancer (57.1%). While 67.1% of surgeons operated early stage ovarian cancer patients, 50% administered neoadjuvant chemotherapy (NACT) to all advanced stage ovarian cancers and 50% administered more cycles of NACT in preference to interval debulking surgery. 93.7% of the surgeons responded that treatment should not be delayed beyond eight weeks. Conclusion: Most Turkish gynecologic oncologists modified their management of gynecologic cancers due to the COVID-19 pandemic. While chemotherapy was preferred for ovarian cancer, postponement of the surgery, with or without non-surgical options, was considered for early stage, low-grade endometrial cancer. Treatment of gynecologic cancers should be decided on a case by case basis, taking into account local COVID-19 infection rates and availability of health facilities. Prognosis is also an important consideration if delay is contemplated. Standard treatment and normal time-frames should be used if possible. If not, a postponement for a maximum of eight weeks or referral to another center were acceptable alternatives.

The impact of morbid obesity on survival of endometrial cancer.

OBJECTIVE: Morbid obesity is identified as patients with a body mass index more than 40 kg/m2. Obesity is known as a risk factor for endometrial cancer due to the increase of the deposited estrogen. This study was conducted to evaluate the effect of morbid obesity on the survival of endometrial cancer. MATERIALS AND METHODS: The archival records and pathologic reports of patients with endometrial cancer who underwent surgery and were followed up in Çukurova University Gynecologic Oncology Center between January 1996 and December 2018 were reviewed, retrospectively. Data regarding body mass index and survival was reported in 520 patients. These patients were stratified into two groups according to their body mass index, <40 and ≥40 kg/m2. The groups' clinic, pathologic features, and survival rates were compared. RESULTS: There were 146 patients in the morbidly obese group and 374 patients in the obese group. The mean age of the groups was 58.5 and 56.2 years, respectively. The mean follow-up time was 51.6 months. Comorbidities were significantly higher in the morbidly obese group. The five-year disease-free and overall survival rates were 78.3% and 85.3% in the morbidly obese group, and 81.6% and 90.1% in the obese group, respectively. Although the groups' clinical and pathologic features were homogeneously distributed, disease-free and overall survival rates were significantly different (p=0.053 and p=0.054, respectively). CONCLUSION: Morbidly obese patients with endometrial cancer were associated with 2.7-fold increased risk of death and 1.7-fold increased risk of recurrence compared with those who had body mass index <40 kg/m2. It is important to deal with the frequent comorbidities in this special group, which could be simply altered by lifestyle changes. Morbidly obese patients with endometrial cancer should be encouraged in lifestyle changes and consulted by dieticians and endocrinologists.

Challenges on the morbidly obese endometrial cancer surgery: Laparotomy or laparoscopy, lymphadenectomy or no lymphadenectomy?

OBJECTIVES: A considerable proportion of endometrial cancer patients are morbidly obese. Management of these cases is a serious dilemma. The aim of this study was to investigate the relevance of laparoscopic route and omission of lymphadenectomy as morbidity-reducing strategies in this special population. MATERIAL AND METHODS: Endometrial cancer patients' archival records were retrospectively reviewed and cases with body mass index ≥ 40 kg/m2 were selected. A comparative evaluation of their characteristics and survival rates were performed. Firstly, according to the surgical approach; laparoscopy or laparotomy, and then regarding to performing lymphadenectomy or not. RESULTS: There were 146 patients enrolled in this study. Whereas, significantly higher postoperative complications and longer hospital stays were determined in the laparotomy compared to laparoscopy groups. Five years disease-free and overall survival were not significantly different (83.6% vs 70.7%, p = 0.184 and 83.9% vs 86.6%, p = 0.571, respectively). On the other hand, operation length, postoperative hospitalization time, both intraoperative and postoperative complications were significantly lower in the non-lymphadenectomy compared to the lymphadenectomy groups. However, five-years disease-free and overall survival were not significantly different (77.3% vs 81.3%, p = 0.586 and 87.5% vs 78%, p = 0.479, respectively). CONCLUSIONS: Laparoscopic approach and omission of lymphadenectomy are worthy policies in the morbidly obese endometrial cancer patients.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients' mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.